Single Unit Recording

In this review we examine how attention is involved in detecting faces, recognizing facial identity and registering and discriminating between facial expressions of emotion. The first section examines whether these aspects of face perception are "automatic", in that they are especially rapid, non-conscious, mandatory and capacity-free. The second section discusses whether limited-capacity selective attention mechanisms are preferentially recruited by faces and facial expressions. Evidence from behavioral, neuropsychological, neuroimaging and psychophysiological studies from humans and single-unit recordings from primates is examined and the neural systems involved in processing faces, emotion and attention are highlighted. Avenues for further research are identified.

In recent years, studies ranging from single-unit recordings in animals to electroencephalography and magnetoencephalography studies in humans have demonstrated the pivotal role of phase synchronization in memory processes. Phase synchronization - here referring to the synchronization of oscillatory phases between different brain regions - supports both working memory and long-term memory and acts by facilitating neural communication and by promoting neural plasticity. There is evidence that processes underlying working and long-term memory might interact in the medial temporal lobe. We propose that this is accomplished by neural operations involving phase-phase and phase-amplitude synchronization. A deeper understanding of how phase synchronization supports the flexibility of and interaction between memory systems may yield new insights into the functions of phase synchronization in general.

Executive functions, such as working memory, must intersect with functions that determine value for the organism. Functional imaging work in humans and single-unit recordings in non-human primates provide evidence that PFC might integrate motivational context with working memory. With functional magnetic resonance imaging (fMRI), we addressed the question of motivation and working memory, using a trial-related design in an object-working memory task. The design permitted the analysis of BOLD signal at separate stages, corresponding to encoding, maintenance, and retrieval. Subjects were motivated by a financial incentive during the task, such that they could gain a high or a low reward. The two different levels of reward also entailed greater or lesser risk of losing money for incorrect responses. In the high, relative to the low, reward condition, subjects shifted response bias, and showed a trend to greater sensitivity. We found main effects in fMRI BOLD signal for reward, which overlapped with BOLD effects for maintenance of information, in the right superior frontal sulcus and bilateral intraparietal sulcus. We also found an interaction between reward and retrieval from working memory in the right dorsolateral prefrontal cortex. Main effects of load and reward occurred in adjacent regions of the ventrolateral PFC during retrieval. The data demonstrate that when subjects perform a simple working memory task, financial incentives motivate performance and interact with some of the same neural networks that process various stages of working memory. Areas of overlap and interaction may integrate information about value, or they may represent a general effect of motivation increasing neural effort. D

In the course of a day, the brain undergoes large-scale changes in functional modes, from attentive wakefulness to the deepest stage of sleep. The present paper evaluates how these state changes aVect the neural bases of sensory and cognitive representations. Are organized neural representations still maintained during sleep? In other words, despite the absence of conscious awareness, do neuronal signals emitted during sleep contain information and have a functional relevance? Through a critical evaluation of the animal and human literature, neural representations at diVerent levels of integration (from the most elementary sensory level to the most cognitive one) are reviewed. Recordings of neuronal activity in animals at presentation of neutral or signiWcant stimuli show that some analysis of the external word remains possible during sleep, allowing recognition of behaviorally relevant stimuli. Event-related brain potentials in humans conWrm the preservation of some sensory integration and discriminative capacity. Behavioral and neuroimaging studies in humans substantiate the notion that memory representations are reactivated and are reorganized during post-learning sleep; these reorganisations may account for the beneWcial eVects of sleep on behavioral performance. Electrophysiological results showing replay of neuronal sequences in animals are presented, and their relevance as neuronal correlates of memory reactivation is discussed. The reviewed literature provides converging evidence that structured neural representations can be activated during sleep. Which reorganizations unique to sleep beneWt memory representations, and to what extent the operations still eYcient in processing environmental information during sleep are similar to those underlying the non-conscious, automatic processing continually at work in wakefulness, are challenging questions open to investigation.

Executive functions, such as working memory, must intersect with functions that determine value for the organism. Functional imaging work in humans and single-unit recordings in non-human primates provide evidence that PFC might integrate motivational context with working memory. With functional magnetic resonance imaging (fMRI), we addressed the question of motivation and working memory, using a trial-related design in an object-working memory task. The design permitted the analysis of BOLD signal at separate stages, corresponding to encoding, maintenance, and retrieval. Subjects were motivated by a financial incentive during the task, such that they could gain a high or a low reward. The two different levels of reward also entailed greater or lesser risk of losing money for incorrect responses. In the high, relative to the low, reward condition, subjects shifted response bias, and showed a trend to greater sensitivity. We found main effects in fMRI BOLD signal for reward, which overlapped with BOLD effects for maintenance of information, in the right superior frontal sulcus and bilateral intraparietal sulcus. We also found an interaction between reward and retrieval from working memory in the right dorsolateral prefrontal cortex. Main effects of load and reward occurred in adjacent regions of the ventrolateral PFC during retrieval. The data demonstrate that when subjects perform a simple working memory task, financial incentives motivate performance and interact with some of the same neural networks that process various stages of working memory. Areas of overlap and interaction may integrate information about value, or they may represent a general effect of motivation increasing neural effort. D

We have developed a three-dimensional silicon electrode array which provides 100 separate channels for neural recording in cortex. The device is manufactured using silicon micromachining techniques, and we have conducted acute recording experiments in cat striate cortex to evaluate the recording capabilities of the array. In a series of five acute experiments, 58.6% of the electrodes in the array were found to be capable of recording visually evoked responses. In the most recent acute study, the average signal-to-noise ratio for recordings obtained from 56 of the electrodes in the array was calculated to be 5.5:1. Using standard window discrimination techniques, an average of 3.4 separable spikes were identified for each of these electrodes. In order to compare the two-dimensional mapping capabilities of the array with those derived from other technologies, orientation preference and ocular dominance maps were generated for each of the evoked responses. Histological evaluation of the implant site indicates some localized tissue insult, but this is likely due to the perfusion procedure since high signal-to-noise ratio neural responses were recorded. The recording capabilities of the Utah Intracortical Electrode Array in combination with the large number of electrodes available for recording make the array a tool well suited for investigations into the parallel processing mechanisms in cortex.

Dorsal anterior cingulate cortex (dACC) is a brain region that subserves cognition and motor control, but the mechanisms of these functions remain unknown. Human neuroimaging and monkey electrophysiology studies have provided valuable insights, but it has been difficult to link the two literatures. Based on monkey single-unit recordings, we hypothesized that human dACC is comprised of a mixture of functionally distinct cells that variously anticipate and detect targets, indicate novelty, influence motor responses, encode reward values, and signal errors. As an initial test of this conceptualization, the current event-related functional MRI study used a reward-based decision-making task to isolate responses from a subpopulation of dACC cells sensitive to reward reduction. As predicted, seven of eight subjects showed significant (P < 10 ؊4 ) dACC activation when contrasting reduced reward (REDrew) trials to fixation (FIX). Confirmatory group analyses then corroborated the predicted ordinal relationships of functional MRI activation expected during each trial type (REDrew > SWITCH > CONrew > FIX). The data support a role for dACC in reward-based decision making, and by linking the human and monkey literatures, provide initial support for the existence of heterogeneity within dACC. These findings should be of interest to those studying reward, cognition, emotion, motivation, and motor control. ʈ This paper was submitted directly (Track II) to the PNAS office.

The hippocampus (HF) of birds and mammals is essential for the map-like representation of environmental landmarks used for navigation. However, species with contrasting spatial behaviors and evolutionary histories are likely to display differences, or 'adaptive specializations', in HF organization reflective of those contrasts. In the search for HF specialization in homing pigeons, we are investigating the spatial response properties of isolated HF neurons and possible right-left HF differences in the representation of space. The most notable result from the recording work is that we have yet to find neurons in the homing pigeon HF that display spatial response properties similar to HF 'place cells' of rats. Of interest is the suggestion of neurons that show higher levels of activity when pigeons are near goal locations and neurons that show higher levels of activity when pigeons are in a holding area prior to be being placed in an experimental environment. In contrast to the rat, the homing pigeon HF appears to be functionally lateralized. Results from a current lesion study demonstrate that only the left HF is sensitive to landmarks that are located within the boundaries of an experimental environment, whereas the right HF is indifferent to such landmarks but sensitive to global environmental features (e.g., geometry) of the experimental space. The preliminary electrophysiological and lateralization results offer interesting departure points for better understanding possible HF specialization in homing pigeons. However, the pigeon and rat HF reside in different forebrain environments characterized by a wulst and neocortex, respectively. Differences in the forebrain organization of pigeons and rats, and birds and mammals in general, must be considered in making sense of possible species differences in how HF participates in the representation of space.

Activation of central noradrenergic pathways by atypical antipsychotics has been hypothesized to play a role in their efficacy in treating the negative symptoms and cognitive impairment of schizophrenia. Because acute administration of the atypical antipsychotic olanzapine has been shown to increase extracellular levels of norepinephrine in the medial prefrontal cortex, we examined the effects of olanzapine on the noradrenergic cells of the locus coeruleus (LC). The effects of olanzapine (0.25-16 mg kg(-1), IV) on the firing rates and patterns of LC neurons were determined by extracellular, single-unit recordings in chloral hydrate-anaesthetized rats. The effects of olanzapine and clozapine on c-Fos expression in the LC, nucleus subcoeruleus part alpha (SubCA), and nucleus A5 (A5) were studied by immunohistochemistry. Olanzapine increased LC cell firing rates, de-regularized firing, and induced burst firing. Induction of c-Fos expression in the LC by olanzapine and clozapine was confirmed and was also found in the SubCA, but not in A5. Acute administration of olanzapine activates the noradrenergic neurons of the rat LC. This increased activity of LC neurons may play an important role in the efficacy of olanzapine and clozapine in treating both the negative symptoms and cognitive impairment observed in schizophrenic patients.

In everyday life, vestibular sensors are activated by both self-generated and externally applied head movements. The ability to distinguish inputs that are a consequence of our own actions (i.e., active motion) from those that result from changes in the external world (i.e., passive or unexpected motion) is essential for perceptual stability and accurate motor control. Recent work has made progress toward understanding how the brain distinguishes between these two kinds of sensory inputs. We have performed a series of experiments in which single-unit recordings were made from vestibular afferents and central neurons in alert macaque monkeys during rotation and translation. Vestibular afferents showed no differences in firing variability or sensitivity during active movements when compared to passive movements. In contrast, the analyses of neuronal firing rates revealed that neurons at the first central stage of vestibular processing (i.e., in the vestibular nuclei) were effectively less sensitive to active motion. Notably, however, this ability to distinguish between active and passive motion was not a general feature of early central processing, but rather was a characteristic of a distinct group of neurons known to contribute to postural control and spatial orientation. Our most recent studies have addressed how vestibular and proprioceptive inputs are integrated in the vestibular cerebellum, a region likely to be involved in generating an internal model of self-motion. We propose that this multimodal integration within the vestibular cerebellum is required for eliminating self-generated vestibular information from the subsequent computation of orientation and posture control at the first central stage of processing.

The activity of spiking neurons is frequently described by renewal point process models that assume the statistical independence and identical distribution of the intervals between action potentials. However, the assumption of independent intervals must be questioned for many different types of neurons. We review experimental studies that reported the feature of a negative serial correlation of neighboring intervals, commonly observed in neurons in the sensory periphery as well as in central neurons, notably in the mammalian cortex. In our experiments we observed the same short-lived negative serial dependence of intervals in the spontaneous activity of mushroom body extrinsic neurons in the honeybee. To model serial interval correlations of arbitrary lags, we suggest a family of autoregressive point processes. Its marginal interval distribution is described by the generalized gamma model, which includes as special cases the log-normal and gamma distributions, which have been widely used to characterize regular spiking neurons. In numeric simulations we investigated how serial correlation affects the variance of the neural spike count. We show that the experimentally confirmed negative correlation reduces single-neuron variability, as quantified by the Fano factor, by up to 50%, which favors the transmission of a rate code. We argue that the feature of a negative serial correlation is likely to be common to the class of spike-frequency-adapting neurons and that it might have been largely overlooked in extracellular single-unit recordings due to spike sorting errors.

Single-unit recordings, stimulation studies, and eye movement measurements all indicate that the firing patterns of many oculomotor neurons in the brain stem encode eye-velocity commands in premotor circuits while the firing patterns of extraocular motoneurons contain both eye-velocity and eye-position components. It is necessary to propose that the eyeposition component is generated from the eye-velocity signal by a leaky hold element or temporal integrator. Prior models of this integrator suffer from two important problems. Since cells appear to have a steady, background signal when eye position and velocity are zero, how does the integrator avoid integrating this background rate? Most models employ some form of lumped, positive feedback the gain of which must be kept within totally unreasonable limits for proper operation. We propose a lateral inhibitory network of homogeneous neurons as a model for the neural integrator that solves both problems. Parameter sensitivity studies and lesion simulations are presented to demonstrate robustness of the model with respect to both the choice of parameter values and the consequences of pathological changes in a portion of the neural integrator pool.

Recent psychological studies suggest that the amygdala is not essential for early stages of emotional facial processing, and that the colliculo-pulvinar pathway might play this role. Nevertheless, the actual role of pulvinar nucleus on the recognition of emotional faces remains obscure. In the present study, we recorded single-unit activity of pulvinar neurons in 2 monkeys during recognition of emotional faces in a delayed non-match-to-sample (DNMS) task, using human face stimuli with differing emotional expressions (sad, angry, happy, surprised and neutral) and simple geometric pattern control figures. A total of 184 single neurons from lateral and medial pulvinar have been sampled. From this total, 41 (22.2%) were found to be "visually responsive", that is, responded to one or more of the visual stimuli. Among the visually responsive neurons, 23 responded non-differentially to all stimuli (facial stimuli and control). Another 18 responded differentially to facial identity and/or emotional expression. Response latencies of the pulvinar neurons to these facial stimuli ranged very widely; firing onsets for 16 (39.0%, 16/41) neurons were shorter than 100 ms, while for 13 (31.7%, 13/41) it was greater than 300 ms. The results thus indicate that 43.9% of the visually responsive pulvinar neurons differentially responded to the emotional expressions of the human faces. Furthermore, wide distribution of the response latencies of the pulvinar neurons suggests that pulvinar neurons might mediate intracortical connections as well as the fast subcortical pathway to the amygdala. These results highlight a role of the pulvinar in the processing of emotional facial stimuli.

Auditory streaming refers to the perceptual parsing of acoustic sequences into "streams", which makes it possible for a listener to follow the sounds from a given source amidst other sounds. Streaming is currently regarded as an important function of the auditory system in both humans and animals, crucial for survival in environments that typically contain multiple sound sources. This article reviews recent findings concerning the possible neural mechanisms behind this perceptual phenomenon at the level of the auditory cortex. The first part is devoted to intra-cortical recordings, which provide insight into the neural "micromechanisms" of auditory streaming in the primary auditory cortex (A1). In the second part, recent results obtained using functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in humans, which suggest a contribution from cortical areas other than A1, are presented. Overall, the findings concur to demonstrate that many important features of sequential streaming can be explained relatively simply based on neural responses in the auditory cortex.

Songbirds constitute a powerful model system for the investigation of how complex vocal communication sounds are represented and generated, offering a neural system in which the brain areas involved in auditory, motor and auditory-motor integration are well known. One brain area of considerable interest is the nucleus HVC. Neurons in the HVC respond vigorously to the presentation of the bird's own song and display song-related motor activity. In the present paper, we present a synthesis of neurophysiological studies performed in the HVC of one songbird species, the canary (Serinus canaria). These studies, by taking advantage of the singing behavior and song characteristics of the canary, have examined the neuronal representation of the bird's own song in the HVC. They suggest that breeding cues influence the degree of auditory selectivity of HVC neurons for the bird's own song over its time-reversed version, without affecting the contribution of spike timing to the information carried by these two song stimuli. Also, while HVC neurons are collectively more responsive to forward playback of the bird's own song than to its temporally or spectrally modified versions, some are more broadly tuned, with an auditory responsiveness that extends beyond the bird's own song. Lastly, because the HVC is also involved in song production, we discuss the peripheral control of song production, and suggest that interspecific variations in song production mechanisms could be exploited to improve our understanding of the functional role of the HVC in respiratory-vocal coordination.

The perception of migraine headache, which is mediated by nociceptive signals transmitted from the cranial dura mater to the brain, is uniquely exacerbated by exposure to light. Here we show that exacerbation of migraine headache by light is prevalent among blind persons who maintain non-image-forming photoregulation in the face of massive rod/cone degeneration. Using singleunit recording and neural tract-tracing in the rat, we identified dura-sensitive neurons in the posterior thalamus, whose activity was distinctly modulated by light, and whose axons projected extensively across layers I through V of somatosensory, visual and associative cortices. The cell bodies and dendrites of such dura/light-sensitive neurons were apposed by axons originating from retinal ganglion cells, predominantly from intrinsically-photosensitive retinal ganglion cells -the principle conduit of non-image-forming photoregulation. We propose that photoregulation of migraine headache is exerted by a non-image-forming retinal pathway that modulates the activity of dura-sensitive thalamocortical neurons.

AbstractöThere is a large body of data on the ¢ring properties of dopamine cells in anaesthetised rats or rat brain slices. However, the extent to which these data relate to more natural conditions is uncertain, as there is little quantitative information available on the ¢ring properties of these cells in freely moving rats. We examined this by recording from the midbrain dopamine cell ¢elds using chronically implanted microwire electrodes. (1) In most cases, slowly ¢ring cells with broad action potentials were profoundly inhibited by the dopamine agonist apomorphine, consistent with previously accepted criteria. However, a small group of cells was found that were di⁄cult to classify because of ambiguous combinations of properties.

This paper presents performance of olfactory neural decoding depending on functional and spatial neural selection. Multi-channel extra-cellular single-unit recording were done by micro-wire electrodes implanted in the mitra/tufted cell layers of the main olfactory bulb (MOB) of anesthetized rates to obtain neural responses to various odors. All neurons are classified according to significant differences response to using t-test (p&lt;;0.01). Odor can be robustly inferred by using subpopulations of neurons. The results indicate that the performance of odor inference is highly dependent on the neural selection. Also, we compared different statistical methods correlations of olfactory decoding accuracy. The results show that t-test is better criterion of assessment of neuron&#39;s capacity than others.

Fifty-eight male Sprague-Dawley rats used in the present study to investigate the role of baroreceptor sensitive neurons of the nucleus tractus solitarius (NTS) in the regulation of cardiovascular inhibition during acupuncture at the auricular point Heart, single unit recording was made in anesthetized Sprague-Dawley rats. A neuron was considered to be excited or inhibited by acupuncture stimulation if it displayed 15% more or less spikes s − 1 , respectively. NTS neurons were classified into cardiac-related (CR) neurons and non-cardiac-related neurons based on whether their rhythmic discharges were synchronized with the R-waves and responding to sodium nitroprusside (NP; 20 μg/kg, i.v.) administration. Manual acupuncture was applied at the auricular point Heart and somatic acupuncture points ST36 and PC6.

Rationale: It has been suggested that the antipsychotic effect of antipsychotics is mediated by the antagonism of the dopamine D 2 receptor in the limbiccortical regions. Risperidone has an atypical property, but its effect on limbic-cortical regions has not been evaluated. Objectives: In this study, we examined the relationship among doses of risperidone and limbic-cortical dopamine D 2 receptor occupancy using positron emission tomography. Methods: Seven patients with schizophrenia were scanned during the steady state with risperidone. Their occupancies in limbic-cortical regions were determined using positron emission tomography with [ 11 C]FLB 457. Results: The average occupancy ranged from 38% to 80% on doses of 1-6 mg/day. The saturation curve plotted against the drug level fit the data well. Conclusions: Our results demonstrate that the D 2 receptor occupancy with risperidone in the limbic-cortical regions seems to be similar to that of previous reports regarding the striatum, and it would be comparable to that of typical antipsychotics.

In binocular rivalry, a subject views two incongruent stimuli through each eye but consciously perceives only one stimulus at a time, with a switch in perceptual dominance every few seconds. To investigate the neural correlates of perceptual dominance in humans, seven subjects were recorded with a 148-channel magnetoencephalography array while experiencing binocular rivalry. A red vertical grating f lickering at one frequency was presented to one eye through a red filter and a blue horizontal grating f lickering at a different frequency was presented to the other eye through a blue filter. Steady-state neuromagnetic responses at the two frequencies were used as tags for the two stimuli and analyzed with high-resolution power spectra. It was found that a large number of channels showed peaks at both frequencies, arranged in a horseshoe pattern from posterior to anterior regions, whether or not the subject was consciously perceiving the corresponding stimulus. However, the amount of power at the stimulus frequency was modulated in relation to perceptual dominance, being lower in many channels by 50-85% when the subject was not conscious of that stimulus. Such modulation by perceptual dominance, although not global, was distributed to a large subset of regions showing stimulusrelated responses, including regions outside visual cortex. The results demonstrate a correlation between the conscious perception of a visual stimulus and the synchronous activity of large populations of neurons as ref lected by steady-state neuromagnetic responses.

The insect repellent DEET is effective against a variety of medically important pests, but its mode of action still draws considerable debate. The widely accepted hypothesis that DEET interferes with the detection of lactic acid has been challenged by demonstrated DEETinduced repellency in the absence of lactic acid. The most recent hypothesis suggests that DEET masks or jams the olfactory system by attenuating electrophysiological responses to 1-octen-3-ol. Our research shows that mosquitoes smell DEET directly and avoid it. We performed single-unit recordings from all functional ORNs on the antenna and maxillary palps of Culex quinquefasciatus and found an ORN in a short trichoid sensillum responding to DEET in a dosedependent manner. The same ORN responded with higher sensitivity to terpenoid compounds. SPME and GC analysis showed that odorants were trapped in conventional stimulus cartridges upon addition of a DEET-impregnated filter paper strip thus leading to the observed reduced electrophysiological responses, as reported elsewhere. With a new stimulus delivery method releasing equal amounts of 1-octen-3-ol alone or in combination with DEET we found no difference in neuronal responses. When applied to human skin, DEET altered the chemical profile of emanations by a ''fixative'' effect that may also contribute to repellency. However, the main mode of action is the direct detection of DEET as indicated by the evidence that mosquitoes are endowed with DEET-detecting ORNs and corroborated by behavioral bioassays. In a sugar-feeding assay, both female and male mosquitoes avoided DEET. In addition, mosquitoes responding only to physical stimuli avoided DEET.

Single-unit responses were recorded from the auditory cortex of rhesus monkeys that were performing an auditory selective attention task. Acoustic stimuli were presented randomly to either the left or right ear through headphones. In a given block of trials one ear was selected as the ear to be attended, and was indicated by lighting either a left or right response key. The animal's task was to press the lighted key whenever stimuli were presented to the attended ear, but to make no response to stimuli presented to the other ear. The attended ear was alternated on successive blocks of trials. Fourteen of 77 units showed significantly greater rates of evoked discharges for an attended stimulus than for an identical non-attended stimulus. The increase in stimulus-evoked activity was not accompanied by any increase in spontaneous activity or by any changes in the pattern of a unit's response. Changes in firing rate occurred at latencies as early as 20 msec.

In this review we examine how attention is involved in detecting faces, recognizing facial identity and registering and discriminating between facial expressions of emotion. The first section examines whether these aspects of face perception are “automatic”, in that they are especially rapid, non-conscious, mandatory and capacity-free. The second section discusses whether limited-capacity selective attention mechanisms are preferentially recruited by faces

A new, improved surgical approach to the cochlear nucleus is developed in the gerbil. This new approach involves malting a small hole in the lateral wall of the temporal bone located within the perimeter of the superior semicircular canal. Microelectrodes are passed through the intact parafloccular lobe of the cerebellum to the cochlear nucleus. One advantage of the new approach is that no removal of any CNS vasculature or neural tissue is necessary. Relations between the bulla, temporal bone and cochlear nucleus are presented in detail. The new approach is demonstrated by making single unit recordings from the cochlear nucleus and classifying response patterns as measured in PST histograms. All of the response types found in cat are found in the gerbil.

Impairments of cellular plasticity appear to underlie the pathophysiology of major depression. Recently, elevated levels of phosphorylated AMPA receptor were implicated in the antidepressant effect of various drugs. Here, we investigated the effects of an antidepressant, Tianeptine, on synaptic function and GluA1 phosphorylation using murine hippocampal slices and in vivo single-unit recordings. Tianeptine, but not imipramine, increased AMPA receptor-mediated neuronal

A crucial issue in neurobiology is to understand the main mechanisms restricting neural plasticity to brief 25 windows of early postnatal life. The visual system is one of the paradigmatic models for studying experience-26 dependent plasticity. The closure of one eye (monocular deprivation, MD) causes a marked ocular 27 dominance (OD) shift of neurons in the primary visual cortex only during the critical period. Here, we report 28 that environmental enrichment (EE), a condition of increased sensory-motor stimulation, reactivates OD 29 plasticity in the adult visual cortex, as assessed with both visual evoked potentials and single-unit 30 recordings. This effect is accompanied by a marked increase in cerebral serotonin (5-HT) levels. Blocking 5-31 HT enhancement in the visual cortex of EE rats completely prevents the OD shift induced by MD. We also 32 found that EE leads to a reduced intracortical GABAergic inhibition and an increased BDNF expression and 33 that the modulation of these molecular factors is neutralized by cortical infusion of the 5-HT synthesis 34 inhibitor pCPA. Our results show that EE rejuvenates the adult visual cortex and that 5-HT is a crucial factor 35 in this process, triggering a cascade of molecular events that allow the reinstatement of neural plasticity. The 36 non-invasive nature of EE makes this paradigm particularly eligible for clinical application. 37 83 the visual cortex, which is classically represented by an OD shift of 84 binocular neurons in response to MD. In this work, we report that EE 85 reinstates full OD plasticity in naïve adult subjects and that serotonin 86 plays an essential role in this effect, acting as the primum movens of a 87 cascade of molecular events that trigger visual cortex plasticity in EE 88 animals. 89 Materials and methods 90 Animal housing 91 A total of 117 Long-Evans hooded rats were used in this study, 92 approved by the Italian Ministry of Public Health. At the postnatal day 93 (P) 60 the animals were assigned to either the environmental 94 enriched group (EE) or to the standard condition group (SC) for 95 three weeks. Environmental enrichment consisted of a large cage 96 (100 × 50 × 82 cm) with two or more floors linked by stairs, containing 97 several food hoppers, running wheels and differently shaped objects, 98 which were repositioned and/or substituted with others once a week. 99 Every cage housed at least 6 adult rats. Standard housing consisted of 100 a standard cage (40 × 30 × 20 cm), housing a maximum of 3 adult rats. 101 In both environmental conditions, food and water were available 102 ad libitum. 103 Animal treatment and drug administration 104 After 2 weeks in EE or SC (~P75) rats were anesthetized with 105 avertin (2,2,2 Tribromoethanol solution, 200 mg/kg). MD was 106 performed through eyelid suturing and the animals were returned 107 to their respective housing conditions. Subjects with even minimal 108 spontaneous reopening were excluded from the study. In different 109 groups of rats, during the same anesthesia, an osmotic minipump 110 (model 2002; Alzet, Palo Alto, CA, USA) connected via PE tubing to a 111 stainless steel cannula (30 ga) was implanted in the visual cortex 112 contralateral to the deprived eye. Osmotic minipumps (flow rate,

The insect repellent DEET is effective against a variety of medically important pests, but its mode of action still draws considerable debate. The widely accepted hypothesis that DEET interferes with the detection of lactic acid has been challenged by demonstrated DEETinduced repellency in the absence of lactic acid. The most recent hypothesis suggests that DEET masks or jams the olfactory system by attenuating electrophysiological responses to 1-octen-3-ol. Our research shows that mosquitoes smell DEET directly and avoid it. We performed single-unit recordings from all functional ORNs on the antenna and maxillary palps of Culex quinquefasciatus and found an ORN in a short trichoid sensillum responding to DEET in a dosedependent manner. The same ORN responded with higher sensitivity to terpenoid compounds. SPME and GC analysis showed that odorants were trapped in conventional stimulus cartridges upon addition of a DEET-impregnated filter paper strip thus leading to the observed reduced electrophysiological responses, as reported elsewhere. With a new stimulus delivery method releasing equal amounts of 1-octen-3-ol alone or in combination with DEET we found no difference in neuronal responses. When applied to human skin, DEET altered the chemical profile of emanations by a ''fixative'' effect that may also contribute to repellency. However, the main mode of action is the direct detection of DEET as indicated by the evidence that mosquitoes are endowed with DEET-detecting ORNs and corroborated by behavioral bioassays. In a sugar-feeding assay, both female and male mosquitoes avoided DEET. In addition, mosquitoes responding only to physical stimuli avoided DEET.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects the whole basal ganglia (BG). Various techniques have been used to study BG physiology and pathophysiology. Among these, extracellular single unit recording remains of particular importance. An impressive number of studies of BG electrophysiological activity have been carried out, both in non-human and in human primates, but the data collected show many omissions and disparities. BG activity has been well defined in the physiological situation, but remains far from clear in the Parkinsonian and virtually unexplored in the dopamine (DA)-replacement situation. This paper provides a brief synopsis of (i) recording techniques and (ii) BG electrophysiological activity in normal, Parkinsonian, and dopamine-replacement situations. We have restricted the data used to those obtained in BG structures of human and non-human primates. Only single unit recordings have been reported and four electrophysiological characteristics retained: mean firing frequency, firing pattern, periodic oscillation, and response to both passive and active movement. We have attempted to summarize (i) the commonly accepted characteristics of each BG structure in the three situations, (ii) discrepancies that exist, and (iii) missing elements. Then, the main successive theories aimed to explain the role played by BG in motor control are presented and discussed in the light of the most recently obtained results using the latest technological advances.

Interaural intensity differences (IIDs) are important cues that animals use to localize high-frequency sounds. Neurons sensitive to IIDs are excited by stimulation of one ear and inhibited by stimulation of the other ear, such that the response magnitude of the cell depends on the relative strengths of the two inputs, which in turn depends on the sound intensities at the ears. In the auditory midbrain nucleus, the inferior colliculus (IC), many IID-sensitive neurons have response functions that decline steeply from maximum to zero spikes as a function of IID. However, there are also many neurons with much more shallow response functions that do not decline to zero spikes. We present evidence from single-unit recordings in the Free-tailed bat's IC that this partially inhibited response pattern is a result of the inhibitory input to these cells being very brief (ϳ2 msec).

Previous studies have identified neurons in the postsubiculum which discharge as a function of the animal&#39;s head direction in the horizontal plane, independent of its behavior and location in the environment. Anatomical studies have shown that the postsubiculum contains reciprocal connections with the anterior thalamic nuclei (ATN). In order to determine how the head direction (HD) cell signal is processed in the brain, single-unit recordings were monitored in the ATN of freely moving rats in order to characterize their behavioral and spatial correlates. Animals were trained to retrieve food pellets thrown randomly into a cylindrical apparatus containing a single orientation cue. Single unit recordings in the ATN showed that approximately 60% of the recorded cells discharged in relation to the animal&#39;s head direction in the horizontal plane. Observation of the animal and quantitative analyses showed that HD cell firing was not dependent on the animal&#39;s behavior, trunk po...

When Camillo Golgi invented the black reaction in 1873 and first described the fine anatomical structure of the nervous system, he described a 'big nerve cell' that later took his name, the Golgi cell of cerebellum ('Golgi'schen Zellen', Gustaf Retzius, 1892). The Golgi cell was then proposed as the prototype of type-II interneurons, which form complex connections and exert their actions exclusively within the local network. Santiago Ramón y Cajal (who received the Nobel Prize with Golgi in 1906) proceeded to a detailed description of Golgi cell morphological characteristics, but functional insight remained very limited for many years. The first rediscovery happened in the 1960s, when neurophysiological analysis in vivo revealed that Golgi cells are inhibitory interneurons. This finding promoted the development of two major cerebellar theories, the 'beam theory' of John Eccles and the 'motor learning theory' of David Marr, in which the Golgi cells regulate the spatial organisation and the gain of input signals to be processed and learned by the cerebellar circuit. However, the matter was not set and a series of pioneering observations using single unit recordings and electron microscopy raised new issues that could not be fully explored until the 1990s. Then, the advent of new electrophysiological and imaging techniques in vitro and in vivo demonstrated the cellular and network activities of these neurons. Now we know that Golgi cells, through complex systems of chemical and electrical synapses, effectively control the spatio-temporal organisation of cerebellar responses. The Golgi cells regulate the timing and number of spikes emitted by granule cells and coordinate their coherent activity. Moreover, the Golgi cells regulate the induction of long-term synaptic plasticity along the mossy fibre pathway. Eventually, the Golgi cells transform the granular layer of cerebellum into an adaptable spatio-temporal filter capable of performing several kinds of logical operation. After more than a century, Golgi's intuition that the Golgi cell had to generate under a new perspective complex ensemble effects at the network level has finally been demonstrated.

This paper reports a multi-channel neural recording system-on-chip (SoC) with digital data compression and wireless telemetry. The circuit consists of a 16 amplifiers, an analog time division multiplexer, an 8-bit SAR AD converter, a digital signal processor (DSP) and a wireless narrowband 400-MHz binary FSK transmitter. Even though only 16 amplifiers are present in our current die version, the whole system is designed to work with 64 channels demonstrating the feasibility of a digital processing and narrowband wireless transmission of 64 neural recording channels. A digital data compression, based on the detection of action potentials and storage of correspondent waveforms, allows the use of a 1.25-Mbit/s binary FSK wireless transmission. This moderate bit-rate and a low frequency deviation, Manchestercoded modulation are crucial for exploiting a narrowband wireless link and an efficient embeddable antenna. The chip is realized in a 0.35−µm CMOS process with a power consumption of 105 µW per channel (269 µW per channel with an extended transmission range of 4 m) and an area of 3.1 × 2.7 mm 2 . The transmitted signal is captured by a digital TV tuner and demodulated by a wideband phase-locked loop (PLL), and then sent to a PC via an FPGA module. The system has been tested for electrical specifications and its functionality verified in in-vivo neural recording experiments.

It is well known that experimentally induced cochlear damage produces structural, physiological, and biochemical alterations in neurons of the cochlear nucleus. In contrast, much less is known with respect to the naturally occurring cochlear pathology presented by congenital deafness. The present study attempts to relate organ of Corti structure and auditory nerve activity to the morphology of primary synaptic endings in the cochlear nucleus of congenitally deaf white cats. Our observations reveal that the amount of sound-evoked spike activity in auditory nerve fibers influences terminal morphology and synaptic structure in the anteroventral cochlear nucleus. Some white cats had no hearing. They exhibited severely reduced spontaneous activity and no sound-evoked activity in auditory nerve fibers. They had no recognizable organ of Corti, presented Ͼ90% loss of spiral ganglion cells, and displayed marked structural abnormalities of endbulbs of Held and their synapses. Other white cats had partial hearing and possessed auditory nerve fibers with a wide range of spontaneous activity but elevated sound-evoked thresholds (60-70 dB SPL). They also exhibited obvious abnormalities in the tectorial membrane, supporting cells, and Reissner's membrane throughout the cochlear duct and had complete inner and outer hair cell loss in the base. The spatial distribution of spiral ganglion cell loss correlated with the pattern of hair cell loss. Primary neurons of hearing-impaired cats displayed structural abnormalities of their endbulbs and synapses in the cochlear nucleus which were intermediate in form compared to normal and totally deaf cats. Changes in endbulb structure appear to correspond to relative levels of deafness. These data suggest that endbulb structure is significantly influenced by sound-evoked auditory nerve activity.

1. Multi-and single-unit recordings in the torus longitudinalis (TL) of the percoid fishes, Holocentrus and Eugerres, showed two kinds of response. The first was a predominantly sustained discharge to dimming in the contralateral visual field. TL receptive fields were always found close to the equator of this field, with their naso-temporal position mapping onto the rostro-caudal axis of TL.

Principal cells of the medial nucleus of the trapezoid body (MNTB) receive their excitatory input through large somatic terminals, the calyces of Held, which arise from axons of globular bushy cells located in the contralateral ventral cochlear nucleus. Discharges of MNTB neurons are characterized by high stimulus evoked firing rates, temporally precise onset responses, and a high degree of phaselocking to either pure tones or stimulus envelopes. Since the calyx of Held synapse is accessible to in vitro and to in vivo recordings, it serves as one of the most elaborate models for studying synaptic transmission in the mammalian brain. Although in such studies, the major emphasis is on synaptic physiology, the interpretation of the data will benefit from an understanding of the MNTB's contribution to auditory signal processing, including possible functional differences in different species. This implies the consideration of possible functional differences in different species. Here, we compare single unit recordings from MNTB principal cells in vivo in three different rodent species: gerbil, mouse and rat. Because of their good low-frequency hearing gerbils are often used in in vivo preparations, while mice and rats are predominantly used in slice preparations. We show that MNTB units in all three species exhibit high firing rates and precise onsettiming. Still there are species-specific specializations that might suggest the preferential use of one species over the others, depending on the scope of the respective investigation.

The recently discovered hormone ghrelin, which is secreted from the stomach during fasting and hypoglycemia opposes the homeostatic functions of leptin by increasing food intake and decreasing energy expenditure. The hypothalamic arcuate nucleus (Arc) mediates the effects of leptin and contains a high density of ghrelin receptors. The leptin-and ghrelin-responsive network involves the hypothalamic neuropeptide Y/a-melanocyte stimulating hormone (NPY/a-MSH) system. In the rat, neurons expressing the orexigenic peptide NPY are mainly located in the ventromedial Arc (ArcM), while pro-opiomelanocortin (POMC) neurons, synthesizing the anorectic peptide a-MSH, predominate in the ventrolateral Arc (ArcL). In extracellular single unit recordings from in vitro slice preparations of the Arc, superfusion of ghrelin (10 28 M) exerted predominantly excitatory effects on ArcM neurons (73%, n ¼ 93), while a high number ArcL neurons were inhibited in response to ghrelin (42%, n ¼ 43). The excitatory effect of ghrelin on neuronal activity was postsynaptic since it was unaffected by synaptic blockade (low Ca 2þ /high Mg 2þ solution). In contrast, the inhibitory response in the ArcL was abolished by the blockade of synaptic interactions indicating a presynaptic mechanism. These results indicate that circulating ghrelin may oppose the actions of leptin by directly activating NPY-neurons of the ArcM and by indirectly inhibiting POMC neurons of the ArcL. q

Imaging studies are consistent with the existence of brain regions specialized for color, but electrophysiological studies have produced conflicting results. Here we address the neural basis for color, using targeted single-unit recording in alert macaque monkeys, guided by functional magnetic resonance imaging (fMRI) of the same subjects. Distributed within posterior inferior temporal cortex, a large region encompassing V4, PITd, and posterior TEO that some have proposed functions as a single visual complex, we found color-biased fMRI hotspots that we call ''globs,'' each several millimeters wide. Almost all cells located in globs showed strong luminance-invariant color tuning and some shape selectivity. Cells in different globs represented distinct visual field locations, consistent with the coarse retinotopy of this brain region. Cells in ''interglob'' regions were not color tuned, but were more strongly shape selective. Neither population was direction selective. These results suggest that color perception is mediated by specialized neurons that are clustered within the extrastriate brain.

A crucial issue in neurobiology is to understand the main mechanisms restricting neural plasticity to brief 25 windows of early postnatal life. The visual system is one of the paradigmatic models for studying experience-26 dependent plasticity. The closure of one eye (monocular deprivation, MD) causes a marked ocular 27 dominance (OD) shift of neurons in the primary visual cortex only during the critical period. Here, we report 28 that environmental enrichment (EE), a condition of increased sensory-motor stimulation, reactivates OD 29 plasticity in the adult visual cortex, as assessed with both visual evoked potentials and single-unit 30 recordings. This effect is accompanied by a marked increase in cerebral serotonin (5-HT) levels. Blocking 5-31 HT enhancement in the visual cortex of EE rats completely prevents the OD shift induced by MD. We also 32 found that EE leads to a reduced intracortical GABAergic inhibition and an increased BDNF expression and 33 that the modulation of these molecular factors is neutralized by cortical infusion of the 5-HT synthesis 34 inhibitor pCPA. Our results show that EE rejuvenates the adult visual cortex and that 5-HT is a crucial factor 35 in this process, triggering a cascade of molecular events that allow the reinstatement of neural plasticity. The 36 non-invasive nature of EE makes this paradigm particularly eligible for clinical application. 37 83 the visual cortex, which is classically represented by an OD shift of 84 binocular neurons in response to MD. In this work, we report that EE 85 reinstates full OD plasticity in naïve adult subjects and that serotonin 86 plays an essential role in this effect, acting as the primum movens of a 87 cascade of molecular events that trigger visual cortex plasticity in EE 88 animals. 89 Materials and methods 90 Animal housing 91 A total of 117 Long-Evans hooded rats were used in this study, 92 approved by the Italian Ministry of Public Health. At the postnatal day 93 (P) 60 the animals were assigned to either the environmental 94 enriched group (EE) or to the standard condition group (SC) for 95 three weeks. Environmental enrichment consisted of a large cage 96 (100 × 50 × 82 cm) with two or more floors linked by stairs, containing 97 several food hoppers, running wheels and differently shaped objects, 98 which were repositioned and/or substituted with others once a week. 99 Every cage housed at least 6 adult rats. Standard housing consisted of 100 a standard cage (40 × 30 × 20 cm), housing a maximum of 3 adult rats. 101 In both environmental conditions, food and water were available 102 ad libitum. 103 Animal treatment and drug administration 104 After 2 weeks in EE or SC (~P75) rats were anesthetized with 105 avertin (2,2,2 Tribromoethanol solution, 200 mg/kg). MD was 106 performed through eyelid suturing and the animals were returned 107 to their respective housing conditions. Subjects with even minimal 108 spontaneous reopening were excluded from the study. In different 109 groups of rats, during the same anesthesia, an osmotic minipump 110 (model 2002; Alzet, Palo Alto, CA, USA) connected via PE tubing to a 111 stainless steel cannula (30 ga) was implanted in the visual cortex 112 contralateral to the deprived eye. Osmotic minipumps (flow rate,

Background: The superior colliculus (SC) has been shown to play a crucial role in the initiation and coordination of eye-and head-movements. The knowledge about the function of this structure is mainly based on single-unit recordings in animals with relatively few neuroimaging studies investigating eye-movement related brain activity in humans.

Activities of spontaneousIy firing neurons in the globus pallidus of intact rats and rats that survived unilateral lesions of the nigrostriatal pathway for 3 days, 1 week, or 6-11 weeks were compared. No significant differences in neuronal firing rate, firing pattern, and number of cells per pass were observed between chloral hydrateanesthetized control and lesioned animals. However, in locally anesthetized animals, pallidal cells fired significantly faster than in chloral hydrate-anesthetized animals, and the lesion caused a decrease in the firing rates of pallidal cells 1 week and 6-9 weeks postlesion. In addition, significant differences in the firing pattern of pallidal cells, as determined by the ratio of the mean to median interspike intervals, were seen between locally anesthetized controls and animals surviving 3 days, 1 week, and 6-9 weeks postlesion. This altered firing pattern tended to return to normal with time. The number of cells per pass was not significantly altered by the lesion. Data from this study suggest that, in locally anesthetized animals, the removal of the tonic dopaminergic input to the basal ganglia causes pallidal cells to decrease their firing rates in a time-dependent fashion and causes reversable firing pattern changes. This suggests that tonically active dopamine neurons, probably acting through the striatopallidal pathway, regulate the firing rate and mechanisms controlling the temporal ordering of spontaneous discharges of globus pallidus neurons.

To test the functional implications of gaze signals that we previously reported in the dorsal premotor cortex (PMd), we trained two rhesus monkeys to point to visual targets presented on a touch screen while controlling their gaze orientation. Each monkey had to perform four different tasks. To initiate a trial, the monkey had to put his hand on a starting position at the center of the touch screen and fixate a fixation point. In one task, the animal had to make a reaching movement to a peripheral target randomly presented at one of eight possible locations on a circle while maintaining fixation at the center of this virtual circle (central fixation + reaching). In the second task, the monkey maintained fixation at the location of the upcoming peripheral target and, later, reached to that location. After a delay, the target was turned on and the monkey made a reaching arm movement (target fixation + reaching). In the third task, the monkey made a saccade to the target without any arm movement (saccade). Finally, in the fourth task, the monkey first made a saccade to the target, then reached to it after a delay (saccade + reaching). This design allowed us to examine the contribution of the oculomotor context to arm-related neuronal activity in PMd. We analyzed the effects of the task type on neuronal activity and found that many cells showed a task effect during the signal (26/60; 43%), set (16/49; 33%) and/or movement (15/54; 28%) epochs, depending on the oculomotor history. These findings, together with previously published data, suggest that PMd codes limb-movement direction in a gaze-dependent manner and may, thus, play an important role in the brain mechanisms of eye-hand coordination during visually guided reaching.

Background: Insect repellents are prophylactic tools against a number of vector-borne diseases. There is growing demand for repellents outperforming DEET in cost and safety, but with the current technologies R&D of a new product takes almost 10 years, with a prohibitive cost of $30 million dollar in part due to the demand for large-scale synthesis of thousands of test compounds of which only 1 may reach the market. R&D could be expedited and cost dramatically reduced with a molecular/physiological target to streamline putative repellents for final efficacy and toxicological tests.

Previous studies have identified neurons in the postsubiculum which discharge as a function of the animal&#39;s head direction in the horizontal plane, independent of its behavior and location in the environment. Anatomical studies have shown that the postsubiculum contains reciprocal connections with the anterior thalamic nuclei (ATN). In order to determine how the head direction (HD) cell signal is processed in the brain, single-unit recordings were monitored in the ATN of freely moving rats in order to characterize their behavioral and spatial correlates. Animals were trained to retrieve food pellets thrown randomly into a cylindrical apparatus containing a single orientation cue. Single unit recordings in the ATN showed that approximately 60% of the recorded cells discharged in relation to the animal&#39;s head direction in the horizontal plane. Observation of the animal and quantitative analyses showed that HD cell firing was not dependent on the animal&#39;s behavior, trunk po...

Flat photoetched gold conductors 12 ¿m wide and 2 ¿m thick, situated on a glass plate and deinsulated at their tips with single 8 ns UV laser pulses, have been utilized to record single unit extra-cellular activity from brain ganglia of the snail Helix pomatia. A fixed array of 36 such conductors, terminating in six rows and six columns in

The hippocampus (HF) of birds and mammals is essential for the map-like representation of environmental landmarks used for navigation. However, species with contrasting spatial behaviors and evolutionary histories are likely to display differences, or 'adaptive specializations', in HF organization reflective of those contrasts. In the search for HF specialization in homing pigeons, we are investigating the spatial response properties of isolated HF neurons and possible right-left HF differences in the representation of space. The most notable result from the recording work is that we have yet to find neurons in the homing pigeon HF that display spatial response properties similar to HF 'place cells' of rats. Of interest is the suggestion of neurons that show higher levels of activity when pigeons are near goal locations and neurons that show higher levels of activity when pigeons are in a holding area prior to be being placed in an experimental environment. In contrast to the rat, the homing pigeon HF appears to be functionally lateralized. Results from a current lesion study demonstrate that only the left HF is sensitive to landmarks that are located within the boundaries of an experimental environment, whereas the right HF is indifferent to such landmarks but sensitive to global environmental features (e.g., geometry) of the experimental space. The preliminary electrophysiological and lateralization results offer interesting departure points for better understanding possible HF specialization in homing pigeons. However, the pigeon and rat HF reside in different forebrain environments characterized by a wulst and neocortex, respectively. Differences in the forebrain organization of pigeons and rats, and birds and mammals in general, must be considered in making sense of possible species differences in how HF participates in the representation of space.

Neuronal responses in primary visual cortex (V1) to optimally oriented high-contrast stimuli in the receptive field (RF) center are suppressed by stimuli in the RF surround, but can be facilitated when the RF center is stimulated at low contrast. The neural circuits and mechanisms for surround modulation are still unknown. We previously proposed that topdown feedback connections mediate suppression from the "far" surround, while "near" surround suppression is mediated primarily by horizontal connections. We implemented this idea in a recurrent network model of V1. A model assumption needed to account for the contrast-dependent sign of surround modulation is a response asymmetry between excitation and inhibition; accordingly, inhibition, but not excitation, is silent for weak visual inputs to the RF center, and surround stimulation can evoke facilitation. A prediction stemming from this same assumption is that surround suppression is weaker for low than for high contrast stimuli in the RF center. Previous studies are inconsistent with this prediction. Using single unit recordings in macaque V1, we confirm this model's prediction. Model simulations demonstrate that our results can be reconciled with those from previous studies. We also performed a systematic comparison of the experimentally-measured surround suppression strength with predictions of the model operated in different parameter regimes. We find that the original model, with strong horizontal and no feedback excitation of local inhibitory neurons, can only partially account quantitatively for the experimentally-measured suppression. Strong direct feedback excitation of V1 inhibitory neurons is necessary to account for the experimentally-measured surround suppression strength.

Striatum (STR) is the major input stage of the basal ganglia (BG). It combines information from cortex, subthalamic nucleus (STN) and external globus pallidus (GPe), and projects to the output stages of the BG, where selection between concurrent motor programs is performed. Parkinson's disease (PD) reduces the concentration of dopamine (DA, a neurotransmitter) in STR and changes in the level of DA correlate with the onset of PD motor disorders. Though STR plays a pivotal role in BG, its behavior under PD and Deep Brain Stimulation (DBS) is still unclear. We develop pointprocess models of the STR neurons as a function of the activity in GPe, cortex, and DBS. We use single unit recordings from a monkey under STN DBS at different frequencies before and after treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to develop PD motor symptoms. The models suggest that STR neurons have prominent bursting activity in normal conditions, positive correlation with cortex (3-10 ms delay), and mild negative correlation with GPe (1-5 ms lag). DA depletion evokes 30-60 Hz oscillations, and increases the propensity of each neuron to be inhibited by surrounding neurons. DBS elicits antidromical activation, masks existent dynamics, reinforces dependencies between nuclei, and entrains at the stimulation frequency in both conditions.

Triptans are 5HT1B/1D receptor agonists commonly prescribed for migraine headache. Although originally designed to constrict dilated intracranial blood vessels, the mechanism and site of action by which triptans abort the migraine pain remain unknown. We showed recently that sensitization of peripheral and central trigeminovascular neurons plays an important role in the pathophysiology of migraine pain. Here we examined whether the drug sumatriptan can prevent and/or suppress peripheral and central sensitization by using single-unit recording in our animal model of intracranial pain. We found that sumatriptan effectively prevented the induction of sensitization (i.e., increased spontaneous firing; increased neuronal sensitivity to intracranial mechanical stimuli) in central trigeminovascular neurons (recorded in the dorsal horn), but not in peripheral trigeminovascular neurons (recorded in the trigeminal ganglion). After sensitization was established in both types of neuron, sumatriptan effectively normalized intracranial mechanical sensitivity of central neurons, but failed to reverse such hypersensitivity in peripheral neurons. In both the peripheral and central neurons, the drug failed to attenuate the increased spontaneous activity established during sensitization. These results suggest that neither peripheral nor central trigeminovascular neurons are directly inhibited by sumatriptan. Rather, triptan action appears to be exerted through presynaptic 5HT1B/1D receptors in the dorsal horn to block synaptic transmission between axon terminals of the peripheral trigeminovascular neurons and cell bodies of their central counterparts. We therefore suggest that the analgesic action of triptan can be attained specifically in the absence, but not in the presence, of central sensitization.