Single Unit Recording

Objective To investigate the changes in the firing activity of noradrenergic neurons in the locus coeruleus (LC) in a rat model of Parkinson disease (PD). Methods 2 and 4 weeks after unilateral lesion of the nigrostriatal pathway in the rat by local injection of 6-hydroxydopamine (6-OHDA) into the right substantia nigra pars compacta (SNc), the firing activity of noradrenergic neurons in LC was recorded by extracellular single unit recording. Results The firing rate of LC noradrenergic neurons increased significantly 2 and 4 weeks after 6-OHDA lesions compared to normal rats, respectively (P < 0.05). The percentage of irregularly firing neurons was obviously higher than that of normal rats during the fourth week after SNc lesion (P < 0.05). Conclusion LC noradrenergic neurons are overactive and more irregular in 6-OHDA-lesioned rats. These changes suggest an implication of the LC in the pathophysiological mechanism of PD.

Imbalance between the dopamine and serotonin (5-HT) neurotransmitter systems has been implicated in the comorbidity of Parkinson&#39;s disease (PD) and psychiatric disorders. L-DOPA, the leading treatment of PD, facilitates the production and release of dopamine. This study assessed the action of L-DOPA on monoamine synaptic transmission in mouse brain slices. Application of L-DOPA augmented the D2-receptor-mediated inhibitory postsynaptic current (IPSC) in dopamine neurons of the substantia nigra. This augmentation was largely due to dopamine release from 5-HT terminals. Selective optogenetic stimulation of 5-HT terminals evoked dopamine release, producing D2-receptor-mediated IPSCs following treatment with L-DOPA. In the dorsal raphe, L-DOPA produced a long-lasting depression of the 5-HT1A-receptor-mediated IPSC in 5-HT neurons. When D2 receptors were expressed in the dorsal raphe, application of L-DOPA resulted in a D2-receptor-mediated IPSC. Thus, treatment with L-DOPA caused ec...

Whisker plucking in developing and adult rats provides a convenient method of temporarily altering tactile input for the purposes of studying experience-dependent plasticity in the somatosensory cortex. Yet, a comprehensive examination of the effect of whisker plucking on the response properties of whisker follicle-innervating trigeminal ganglion (NVg) neurons is lacking. We used extracellular single unit recordings to examine responses of NVg neurons to controlled whisker stimuli in three groups of animals: (1) rats whose whiskers were plucked from birth for 21 days; (2) rats whose whiskers were plucked once at 21 days of age; and (3) control animals. After at least 3 weeks of whisker regrowth, NVg neurons in plucked rats displayed normal, single whisker receptive fields and could be characterized as slowly (SA) or rapidly adapting (RA). The proportion of SA and RA neurons was unaffected by whisker plucking. Both SA and RA NVg neurons in plucked rats displayed normal response latencies and angular tuning but abnormally large responses to whisker movement onsets and offsets. SA neurons were affected to a greater extent than RA neurons. The effect of whisker plucking was more pronounced in animals whose whiskers were plucked repeatedly during development than in rats whose whiskers were plucked once. Individual neurons in plucked animals displayed abnormal periods of prolonged rhythmic firing following deflection onsets and aberrant bursts of activity during the plateau phase of the stimulus. These results indicate that whisker plucking exerts a long-term effect on responses of trigeminal ganglion neurons to peripheral stimulation.

Simultaneous recording from multiple single neurones presents many technical difficulties. However, obtaining such data has many advantages, which make it highly worthwhile to overcome the technical problems. This report describes methods which we have developed to permit recordings in awake behaving monkeys using the 'Eckhorn' 16 electrode microdrive. Structural magnetic resonance images are collected to guide electrode placement. Head fixation is achieved using a specially designed headpiece, modified for the multiple electrode approach, and access to the cortex is provided via a novel recording chamber. Growth of scar tissue over the exposed dura mater is reduced using an anti-mitotic compound. Control of the microdrive is achieved by a computerised system which permits several experimenters to move different electrodes simultaneously, considerably reducing the load on an individual operator. Neurones are identified as pyramidal tract neurones by antidromic stimulation through chronically implanted electrodes; stimulus control is integrated into the computerised system. Finally, analysis of multiple single unit recordings requires accurate methods to correct for non-stationarity in unit firing. A novel technique for such correction is discussed.

Wireless video streaming has traditionally been considered an extremely power-hungry operation. Existing approaches optimize the camera and communication modules individually to minimize their power consumption. However, the joint redesign and optimization of wireless communication as well as the camera is what that provides more power saving. We present an ultra-low-power wireless video streaming camera. To achieve this, we present a novel &quot;analog&quot; video backscatter technique that feeds analog pixels from the photo-diodes directly to the backscatter hardware, thereby eliminating power consuming hardware components such as ADCs and amplifiers. We prototype our wireless camera using off-the-shelf hardware and show that our design can stream video at up to 13 FPS and can operate up to a distance of 150 feet from the access point. Our COTS prototype consumes 2.36mW. Finally, to demonstrate the potential of our design, we built two proof-of-concept applications: video streamin...

We present the NeuralWISP, a wireless neural interface operating from far-field radio-frequency RF energy. The Neu-ralWISP is compatible with commercial RF identification readers and operates at a range up to 1 m. It includes a custom low-noise, low-power amplifier integrated circuit for processing the neural signal and an analog spike detection circuit for reducing digital computational requirements and communications bandwidth. Our system monitors the neural signal and periodically transmits the spike density in a user-programmable time window. The entire system draws an average 20 A from the harvested 1.8-V supply.

Intracranial headaches such as that of migraine are generally accepted to be mediated by prolonged activation of meningeal nociceptors but the mechanisms responsible for such nociceptor activation are poorly understood. In this study, we examined the hypothesis that meningeal nociceptors can be activated locally through a neuroimmune interaction with resident mast cells, granulated immune cells that densely populate the dura mater. Using in vivo electrophysiological single unit recording of meningeal nociceptors in the rat we observed that degranulation of dural mast cells using intraperitoneal administration of the basic secretagogue agent compound 48/80 (2 mg/kg) induced a prolonged state of excitation in meningeal nociceptors. Such activation was accompanied by increased expression of the phosphorylated form of the extracellular signal-regulated kinase (pERK), an anatomical marker for nociceptor activation. Mast cell -induced nociceptor interaction was also associated with downstream activation of the spinal trigeminal nucleus as indicated by an increase in c-fos expression. Our findings provide evidence linking dural mast cell degranulation to prolonged activation of the trigeminal pain pathway believed to underlie intracranial headaches such as that of migraine.

The auditory system of adult midshipman fish Porichthys notatus Girard is an important sensory receiver system used during intraspecific social communication to encode conspecific vocalizations, but the response properties and function of this system in the pre-adult stages are unknown. Midshipman fish, like other teleosts, use the saccule as the main acoustic end organ of the inner ear. In this study, we examined the discharge properties and the frequency response dynamics of auditory saccular afferent neurons in pre-adult midshipman (~4-12 months of age) to determine whether encoding of auditory information, inclusive of conspecific vocalizations, changes across life history stages. Extracellular single unit recordings were made from saccular afferents while sound was presented via an underwater speaker. Comparisons with adult data show that the resting discharge rate and auditory threshold sensitivity increased with age/size, while temporal encoding of frequency did not show any significant shifts. The results indicate that the saccular afferents of juveniles, like those of non-reproductive adults, are best adapted to temporally encode the low frequency components (≤100•Hz) of midshipman vocalizations. This report represents the first in vivo investigation of age-related changes in the encoding properties of individual auditory neurons for any fish species.

The neuronal effects of somatostatin-14 (SS-14) and its influence on responses to acetylcholine (AcCho) were studied in vivo in the rat parietal cortex and dorsal hippocampus, using single-unit recording and microiontophoresis. SS-14 inhibited spontaneous firing of nearly all cells tested, while AcCho facilitated their firing. In contrast to its direct slowing effect, sustained iontophoretic application of SS-14 enhanced AcCho-induced excitations in 78% of all cells tested. This AcCho-enhancing effect of SS-14 was dose dependent. SS-14 did not enhance the responsiveness to pulses of the excitatory amino acid glutamate. Neurons tonically driven by iontophoretic currents of AcCho responded to concurrent pulses of SS-14 with an increase in firing. Thus, iontophoretic application of SS-14 can produce qualitatively different effects on the spontaneous activity of its target cells depending on the simultaneous effects of other chemical messengers. These condition-dependent interactions ma...

Quantitative studies were made of the distribution of labeled intracortical axons after focal injections of horseradish peroxidase (HRP) into mouse barrel cortex, in vitro. The pattern of labeled fibers was compared to that of labeled cell bodies with respect to the barrel map in layer IV. We analyzed 4 cortices with injections in supragranular layers and centered above a single barrel row. Computer microscope/image analysis routines were used to collect the data and to perform various statistical analyses on them. The distributions of both labeled cells and fibers in layer IV and in the infragranular layers show strong connectional tendencies between barrels representing a whisker row. This result is consistent with single unit recordings from barrel cortex. Fiber labeling is more widespread than cell body labeling in layer IV. In addition, the fibers show a directional bias into the adjacent anterior barrel row (e.g., C ~ D, D E). In earlier 2-deoxyglucose (2-DG) studies of behaving animals, the anterior barrel rows were more heavily labeled; inter-row projections are therefore predominantly from less active to more active barrel columns. These data show that labeled fiber distribution differs from the distribution pattern of labeled cell bodies. The findings indicate that integration of information between whisker rows within barrel cortex involves asymmetrical connections within layer IV and infragranular layers.

There is evidence that elevated tissue concentrations of glutamate may contribute to pain and sensitivity in certain musculoskeletal pain conditions. In the present study the food additive monosodium glutamate (MSG) was injected intravenously into rats to determine whether it could significantly elevate interstitial concentrations of glutamate in the masseter muscle and whether MSG administration could excite and/or sensitize slowly conducting masseter afferent fibers through Nmethyl-D-aspartate (NMDA) receptor activation. The interstitial concentration of glutamate after systemic injection of isotonic phosphate-buffered saline (control) or MSG (10 and 50 mg/kg) was measured with a glutamate selective biosensor. The pre-injection baseline interstitial concentration of glutamate in the rat masseter muscle was 24±11 μM. Peak interstitial concentration after injection of 50 mg/kg MSG was 63±18 μM and remained elevated above baseline for ~18 minutes In vivo single unit recording experiments were undertaken to assess the effect of MSG (50 mg/kg) on masseter afferent fibers. Injection of MSG evoked a brief discharge in one afferent fiber, and significantly decreased (~25%) the average afferent mechanical threshold (n=10) during the first 5 min after injection of MSG. Intravenous injection of ketamine (1 mg/kg), 5 minutes prior to MSG, prevented the MSG-induced decreases in the mechanical threshold of masseter afferent fibers. The present results indicate that a 2-3 fold elevation in interstitial glutamate levels in the masseter muscle is sufficient to excite and induce afferent mechanical sensitization through NMDA receptor activation. These findings suggest that modest elevations of interstitial glutamate concentration could alter musculoskeletal pain sensitivity in humans.

Highlights d In a naturalistic memory task, we show that hippocampal neurons are not modulated by context d We observe similar single-neuron responses to the same concepts in different tasks d Neurons do not show conjunctive coding (i.e., responding only in specific contexts or tasks)

We present a nonlinear ÿeld model based on linear couplings for inhibition e ects in early vision. The model is ÿtted to data from single unit recordings in the primary visual cortex of the cat. We focus on the prominent e ect that responses to second stimuli are ampliÿed, reduced, or una ected depending on the temporal and spatial distance of the stimuli. The model is adjusted using an elaborated self-adaptive evolution strategy resulting in an accurate, easy to interpret, and well generalizing model.

I have been worked on two similarity measure techniques for fMRI images. One is SPM-based, which measure the similarity of Statistical Parametric Maps of the fMRI images, the other one is ICA-based, which measure the similarity of the voxels based on the Independent Component Analysis. In the SPMbased tool, I have implemented two image grouping techniques, graph-theory clustering and Replicator Dynamics, in order to group similar fMRI images. In ICA-based tool, I used bipartite graph matching to measure the similarity between fMRI images based on the similarities of the components.

In rodents, exploring through continuous whisking is a process resulted from sensorimotor networking among different layers of somatosensory cortex (SC) such as layer 5 (L5) or barrel field, and regions like the nucleus basalis of Meynert (NBM). NBM is densely packed with cholinergic fibers and its dysfunction leads to diminished acetylcholine release within SC, tactile deficits and Alzheimer's disease (AD)-like memory impairment. Using extracellular single-unit recording, we investigated mechanisms underlying changes in response characteristics of L5b neurons to single or paired deflection of selected principle and adjacent whiskers (PW and AW), following NBM electrical stimulation in normal rats or ibotenic acid-induced NBM lesion leading to potential tactile deficiency and memory loss during passive avoidance learning (PAL) in AD-like neuropathology. Our results indicated that NBM electrical stimulation decreased ON and OFF response magnitude in nearly half of the units upon vibrissal deflection. The larger the response was evoked to whisker deflection before NBM stimulation, the smaller it gets after stimulation. Neuronal spontaneous activity was not changed with NBM stimulation or lesion. Leading to more sublinear response summation and decreased condition-test ratio, NBM lesion decreased ON response magnitude and facilitation, increased AW surround inhibition in paired whisker deflection, increased excitatory and decreased inhibitory receptive fields, weakened information processing during whisking, and

The analysis of a peripheral visual location can be improved in two ways: either by orienting one's gaze (usually by making a foveating saccade) or by 'covertly' shifting one's attention to the peripheral location without making an eye movement. The premotor theory of attention holds that saccades and spatial shifts of attention share a common functional module with a distinct neuronal basis. Using single-unit recording from the brains of trained rhesus monkeys, we investigated whether the superior colliculus, the major subcortical center for the control of saccades, is part of this shared network for attention and saccades. Here we show that a distinct type of neuron in the intermediate layer of the superior colliculus, the visuomotor neuron, which is known to be centrally involved in the preparation of saccades, is also active during covert shifts of attention.

; the resulting alignments were manually inspected using the ED program from the MUST package 22 . Only unambiguously aligned positions were used in phylogenetic analyses. A fusion F1 was built for 12 operational taxonomic units (OTUs) (Fig. ) by concatenation of the 13 proteins (5,171 sites: 1,597 constant, 3,574 polymorphic). A fusion F2 (1,938 sites: 672 constant, 1,266 polymorphic) was constructed to include the glaucophyte C. paradoxa. It contained data from 6 proteins (actin, a-tubulin, b-tubulin, EF-1a, Hsp70 and ATPase vatB) and 13 OTUs (Fig. ). Fusion alignments and accession numbers for all sequences used are given in Supplementary Information. Distance, MP and ML analyses were carried out with all individual and concatenated data sets using MUST (ref. 22), PAUP 3.1 (ref. 23), and PROTML 2.3 (ref. 24), respectively. To carry out exhaustive ML analyses of all possible tree topologies, several constraints were imposed to reduce the number of possible trees (see Figs and). Calculation of aparameter values and other ML analyses taking into account ASRV were conducted using the program PUZZLE (ref. 25). Maximum-likelihood bootstrap proportions were computed using the RELL method 26 upon the 5,000 top-ranking trees. For distance and parsimony analyses, 1,000 bootstrap replicates were computed. Kishino±Hasegawa tests 14 were carried out comparing lnL of the best 50 trees containing monophyletic GR with lnL of the best 50 trees without monophyletic GR, using PROTML 2.3 (ref. 24) (without considering ASRV) and PUZZLE 25 (with a G-law to correct for ASRV). In the case of fusion F2, we used Kishino±Hasegawa tests to estimate the D lnL between the best 50 trees containing monophyletic GR + Glaucophyta and the best 50 trees without this monophyletic group.

The extraordinary navigational ability of homing pigeons provides a unique spatial cognitive system to investigate how the brain is able to represent past experiences as memory. In this paper, we first summarize a large body of lesion data in an attempt to characterize the role of the avian hippocampal formation (HF) in homing. What emerges from this analysis is the critical importance of HF for the learning of map-like, spatial representations of environmental stimuli used for navigation. We then explore some interesting properties of the homing pigeon HF, using for discussion the notion that the homing pigeon HF likely displays some anatomical or physiological specialization(s), compared to the laboratory rat, that account for its participation in homing and the representation of large-scale, environmental space. Discussed are the internal connectivity among HF subdivisions, the occurrence of neurogenesis, the presence of rhythmic theta activity and the electrophysiological profile of HF neurons. Comparing the characteristics of the homing pigeon HF with the hippocampus of the laboratory rat, two opposing perspectives can be supported. On the one hand, one could emphasize the subtle differences in the properties of the homing pigeon HF as possible departure points for exploring how the homing pigeon HF may be adapted for homing and the representation of large-scale space. Alternatively, one could emphasize the similarities with the rat hippocampus and suggest that, if homing pigeons represent space in a way different from rats, then the neural specializations that would account for the difference must lie outside HF. Only future research will determine which of these two perspectives offers a better approximation of the truth.

The meaning behind neural single unit activity has constantly been a challenge, so it will persist in the foreseeable future. As one of the most sourced strategies, detecting neural activity in high-resolution neural sensor recordings and then attributing them to their corresponding source neurons correctly, namely the process of spike sorting, has been prevailing so far. Support from ever-improving recording techniques and sophisticated algorithms for extracting worthwhile information and abundance in clustering procedures turned spike sorting into an indispensable tool in electrophysiological analysis. This review attempts to illustrate that in all stages of spike sorting algorithms, the past 5 years innovations&#39; brought about concepts, results, and questions worth sharing with even the non-expert user community. By thoroughly inspecting latest innovations in the field of neural sensors, recording procedures, and various spike sorting strategies, a skeletonization of relevant ...

Two eye fields have been identified in the frontal lobes of primates: one is situated dorsomedially within the frontal cortex and will be Ž. referred to as the eye field within the dorsomedial frontal cortex DMFC ; the other resides dorsolaterally within the frontal cortex and is Ž. commonly referred to as the frontal eye field FEF. This review documents the similarities and differences between these eye fields. Although the DMFC and FEF are both active during the execution of saccadic and smooth pursuit eye movements, the FEF is more dedicated to these functions. Lesions of DMFC minimally affect the production of most types of saccadic eye movements and have no effect on the execution of smooth pursuit eye movements. In contrast, lesions of the FEF produce deficits in generating saccades to briefly presented targets, in the production of saccades to two or more sequentially presented targets, in the selection of simultaneously presented targets, and in the execution of smooth pursuit eye movements. For the most part, these deficits are prevalent in both monkeys and humans. Single-unit recording experiments have shown that the DMFC contains neurons that mediate both limb and eye movements, whereas the FEF seems to be involved in the execution of eye movements only. Imaging experiments conducted on humans have corroborated these findings. A feature that distinguishes the DMFC from the FEF is that the DMFC contains a somatotopic map with eyes represented rostrally and hindlimbs represented caudally; the FEF has no such topography. Furthermore, experiments have revealed that Ž. the DMFC tends to contain a craniotopic i.e., head-centered code for the execution of saccadic eye movements, whereas the FEF Ž. contains a retinotopic i.e., eye-centered code for the elicitation of saccades. Imaging and unit recording data suggest that the DMFC is more involved in the learning of new tasks than is the FEF. Also with continued training on behavioural tasks the responsivity of the DMFC tends to drop. Accordingly, the DMFC is more involved in learning operations whereas the FEF is more specialized for the execution of saccadic and smooth pursuit eye movements.

Although electrophysiologists have been recording intracellular neural activity routinely ever since the ground-breaking work of Hodgkin and Huxley, and extracellular multichannel electrodes have also been used frequently and extensively, a practical experimental method to track changes in membrane potential along a complete single neuron is still lacking. Instead of obtaining multiple intracellular measurements on the same neuron, we propose an alternative method by combining single-channel somatic patch-clamp and multichannel extracellular potential recordings. In this work, we show that it is possible to reconstruct the complete spatiotemporal distribution of the membrane potential of a single neuron with the spatial resolution of an extracellular probe during action potential generation. Moreover, the reconstruction of the membrane potential allows us to distinguish between the two major but previously hidden components of the current source density (CSD) distribution: the resistive and the capacitive currents. This distinction provides a clue to the clear interpretation of the CSD analysis, because the resistive component corresponds to transmembrane ionic currents (all the synaptic, voltage-sensitive and passive currents), whereas capacitive currents are considered to be the main contributors of counter-currents. We validate our model-based reconstruction approach on simulations and demonstrate its application to experimental data obtained in vitro via paired extracellular and intracellular recordings from a single pyramidal cell of the rat hippocampus. In perspective, the estimation of the spatial distribution of resistive membrane currents makes it possible to distiguish between active and passive sinks and sources of the CSD map and the localization of the synaptic input currents, which make the neuron fire.

The meaning behind neural single unit activity has constantly been a challenge, so it will persist in the foreseeable future. As one of the most sourced strategies, detecting neural activity in high-resolution neural sensor recordings and then attributing them to their corresponding source neurons correctly, namely the process of spike sorting, has been prevailing so far. Support from ever-improving recording techniques and sophisticated algorithms for extracting worthwhile information and abundance in clustering procedures turned spike sorting into an indispensable tool in electrophysiological analysis. This review attempts to illustrate that in all stages of spike sorting algorithms, the past 5 years innovations' brought about concepts, results, and questions worth sharing with even the non-expert user community. By thoroughly inspecting latest innovations in the field of neural sensors, recording procedures, and various spike sorting strategies, a skeletonization of relevant knowledge lays here, with an initiative to get one step closer to the original objective: deciphering and building in the sense of neural transcript.

Parkinson's disease patients are known to have not only motor but also urinary autonomic disorders, suggesting central dopaminergic pathways being involved in the micturition function. However, there is little evidence that the substantia nigra pars compacta (SNC) and the ventral tegmental area (VTA), the major dopamine-containing nuclei in the midbrain, should participate in regulating micturition. We investigated micturition-related electrophysiological properties in the SNC and VTA. In 20 male cats under ketamine anaesthesia, in which spontaneous isovolumetric micturition reflex was generated, we performed electrical stimulation and extracellular single-unit recording in the SNC and the VTA, and correlation analysis of the neuronal firings and antidromic stimulation between the SNC/VTA and the pontine storage centre (PSC). Electrical stimulations in the SNC elicited termination of the micturition reflex, whereas those in the VTA elicited both termination and facilitation of the reflex. Forty-nine neurons in the SNC/VTA showed firing in response to the bladder storage/micturition cycles. The major neurons were tonic storage (55%) and phasic storage neurons (22%), which were found diffusely in the SNC/VTA. The rest were tonic micturition (16%) and phasic micturition neurons (6%), which were concentrated in the caudal part (A2-4 in the Horsley-Clarke coordinates). These neuronal types were further subclassified into augmenting, constant, binary and decrementing neurons according to their temporal discharge rate change. The decrementing neurons were concentrated in the caudal part (A2-4), whereas the augmenting neurons in the rostral part (A4-6). Some of the recorded neurons had preceding firing pattern, which was more frequently found in the tonic type than in the phasic-type neurons. Twenty-four of the neuronal firings in the SNC/VTA were recorded simultaneously with those in the PSC. However, there was no apparent time-correlation between both sets of neuronal firings. In 15 of the simultaneous recording sites, electrical stimulation was applied to one site to see if antidromic response might be evoked in another site. However, there was no orthodromic or antidromic response in either SNC/VTA or PSC. In conclusion, the present study indicates that neurons in the SNC and the VTA are involved in supra-pontine control of micturition, particularly of urinary storage phase. It is also likely that the major role of the SNC is inhibition of the micturition reflex, whereas that of the VTA is both facilitation and inhibition of the micturition reflex.

When the brain receives input from multiple sensory systems, it is faced with the question of whether it is appropriate to process the inputs in combination, as if they originated from the same event, or separately, as if they originated from distinct events. Furthermore, it must also have a mechanism through which it can keep sensory inputs calibrated to maintain the accuracy of its internal representations. We have developed a neural network architecture capable of i) approximating optimal multisensory spatial integration, based on Bayesian causal inference, and ii) recalibrating the spatial encoding of sensory systems. The architecture is based on features of the dorsal processing hierarchy, including the spatial tuning properties of unisensory neurons and the convergence of different sensory inputs onto multisensory neurons. Furthermore, we propose that these unisensory and multisensory neurons play dual roles in i) encoding spatial location as separate or integrated estimates a...

Single unit recordings of neurons in primary visual cortex have demonstrated complex temporal patterns in the interspike interval return maps when presented with periodic input. Two models are tested to account for these patterns. An integrate-and-fire model is only able to replicate the in vivo data if its synaptic input is a chaotic function of time (such as a time series derived from the sinusoidally driven During equation). Simpler purely periodic inputs are insufficient to replicate the experimental data. A Hodgkin-Huxley ionic model with a periodic input can replicate some of the features of the neural data, however it seems to be lacking as a complete model. These results indicate that the in vivo dynamics are not a result of the intrinsic properties of the neuron, but arise from a chaotic input to the neuron.

1. The mating (advertisement) calls of two sibling species of gray treefrogs, Hyla versicolor and Hyla chrysoscelis, are spectrally identical but differ in trill rate; being higher for H. chrysoscelis. Single-unit recordings were made from the torus semicircularis of both species to investigate the neural mechanisms by which this species-specific temporal feature is analyzed. Using sinusoidally amplitude-modulated (AM) white noise as a stimulus, the temporal selectivity of these midbrain auditory neurons could be described by five response categories: 'AM nonselective' (34%); 'AM high-pass' (7%); ' AM low-pass' (6%); ' AM band-suppression' (12%); 'AM tuned' (40%). 2. The distributions of temporal tuning values (i.e., modulation rate at which each AM-tuned unit responds maximally) are broad; in both species, neurons were found which were tuned to modulation rates greater than those found in their advertisement calls. Nevertheless, the temporal tuning values for H. versicolor (median = 25 Hz) were significantly lower than those for H. chrysoscelis (median = 32.5 Hz). 3. The temporal selectivities of AM band-suppression neurons were found to be temperature dependent. The modulation rate at which a response minimum was observed shifted to higher values as the temperature was elevated. These results extend our earlier findings of temperature-dependent temporal selectivity in the gray treefrog. 4. The selectivity of band-suppression and AMtuned neurons to various rates of amplitude modulation was largely, but not completely, independent of whether sinusoidal or natural forms of AM were used.

Orienting attention to a new target requires prior disengagement of attention from the current focus. Previous studies indicate that the superior colliculus (SC) plays an important role in attention. However, recordings of responses of SC neurons during attentional disengagement have not yet been reported. Here, we analyzed rat SC neuronal activity during performance of an attention-shift task with and without disengagement. In this task, conditioned stimuli (CSs; right and/or left light-flash or sound) were sequentially presented.To obtain an intracranial self-stimulation reward, rats were required to lick a spout when an infrequent conditioned stimulus appeared (reward trials). In the disengagement reward trials, configural stimuli consisting of an infrequent stimulus and frequent stimulus in the former trials were presented; in the non-disengagement reward trials, only an infrequent stimulus was presented. Of the 186 SC neurons responding to the CSs, 41 showed stronger responses to the CSs in the disengagement reward trials than in the nondisengagement reward trials (disengagement-related neurons). Furthermore, lick latencies in the disengagement reward trials were negatively correlated with response magnitudes to the CSs in half of the disengagement-related neurons. These disengagement-related neurons were located mainly in the deep layers of the SC. Another 70 SC neurons responded to the CSs in both disengagement and non-disengagement reward trials, suggesting that these neurons were involved in attention engagement. Our results suggest complementary mechanisms of attentional shift based on two subpopulations of neurons in the SC.

Cocaine's effects on striatal neurons related to vertical head movement were studied during a task requiring vertical head movement. The proportion of long-distance head movements was increased by low doses but decreased by the high dose, which produced stereotypic head bobbing. At all doses, normally low firing rates related to movement were elevated to a greater degree than were normally high firing rates. At the high dose, normally high firing rates were strongly suppressed, a restriction which may contribute to the decreased behavioral diversity characteristic of stereotypy. q 1997 Elsevier Science B.V.

Cocaine's effects on striatal neurons related to vertical head movement were studied during a task requiring vertical head movement. The proportion of long-distance head movements was increased by low doses but decreased by the high dose, which produced stereotypic head bobbing. At all doses, normally low firing rates related to movement were elevated to a greater degree than were normally high firing rates. At the high dose, normally high firing rates were strongly suppressed, a restriction which may contribute to the decreased behavioral diversity characteristic of stereotypy. q 1997 Elsevier Science B.V.

Single unit recordings in awake, unrestrained rats confirmed and extended previous findings regarding the functional organization of the lateral striatum. In individual electrode tracks, clusters of neurons related functionally to an individual body part were interspersed with clusters related to other body parts. The overlapping distributions of these neurons were arranged somatotopically in the dorsal-ventral dimension. The distribution of hind limb neurons was most dorsal and showed no overlap with the distribution of neurons related to oral sensorimotor activity. Oral representation was most ventral of all body parts and extended to the ventral boundary of the lateral striatum. Representations of other body parts overlapped with that of the hind limb dorsally but differed primarily in the degree to which they extended ventrally. Forelimb representation extended farther ventrally than that of the hind limb, but did not extend as far ventrally as that of the neck. Despite substantial overlap in the dorsal-to-ventral order of hind limb-forelimb-neck-face representations, single neurons showed no evidence of overlap, or convergence, of body parts. These data provide a more complete description of the dorsal-ventral somatotopy in the lateral striatum of the rat, which as shown previously, extends throughout the medial-lateral, and much of the anterior-posterior dimensions of the lateral striatum.

Single unit recordings in awake, unrestrained rats confirmed and extended previous findings regarding the functional organization of the lateral striatum. In individual electrode tracks, clusters of neurons related functionally to an individual body part were interspersed with clusters related to other body parts. The overlapping distributions of these neurons were arranged somatotopically in the dorsal-ventral dimension. The distribution of hind limb neurons was most dorsal and showed no overlap with the distribution of neurons related to oral sensorimotor activity. Oral representation was most ventral of all body parts and extended to the ventral boundary of the lateral striatum. Representations of other body parts overlapped with that of the hind limb dorsally but differed primarily in the degree to which they extended ventrally. Forelimb representation extended farther ventrally than that of the hind limb, but did not extend as far ventrally as that of the neck. Despite substantial overlap in the dorsal-to-ventral order of hind limb-forelimb-neck-face representations, single neurons showed no evidence of overlap, or convergence, of body parts. These data provide a more complete description of the dorsal-ventral somatotopy in the lateral striatum of the rat, which as shown previously, extends throughout the medial-lateral, and much of the anterior-posterior dimensions of the lateral striatum.

Cocaine's effects on striatal neurons related to vertical head movement were studied during a task requiring vertical head movement. The proportion of long-distance head movements was increased by low doses but decreased by the high dose, which produced stereotypic head bobbing. At all doses, normally low firing rates related to movement were elevated to a greater degree than were normally high firing rates. At the high dose, normally high firing rates were strongly suppressed, a restriction which may contribute to the decreased behavioral diversity characteristic of stereotypy. q 1997 Elsevier Science B.V.

To study the striatal role in amphetamine's stimulant effects on motor behavior, single neurons were recorded in the dorsolateral Ž. striatum of unrestrained rats before and after amphetamine injection 0.5 or 1.0 mgrkg, i.p.. Comparisons of firing were made between similar motor behaviors before and after injection. Mean locomotor firing rates increased 5% to 276% within 30 min after injection and reversed within 2 h. Firing related to specific head-or forelimb-movements, which were similar in all measured parameters before and after injection, was elevated several hundred percent after injection and then reversed, the time course paralleling that of the stimulant effect on these movements. Elevation of movement-related striatal firing rates by low doses of the psychomotor stimulant is in line with established increases in firing rate normally observed for striatal neurons related to motor behavior.

Long-term potentiation (LTP) is a highly studied cellular process, yet determining the transduction and gamma aminobutyric acid (GABAergic) pathways that are the essential versus modulatory for LTP elicited by theta burst stimulation (TBS) in the hippocampal Cornu Ammonis 1 (CA1) area is still elusive, due to the use of different TBS intensities, patterns or different rodent/ cellular models. We now characterised the developmental maturation and the

Vocalization, a means of social communication, is prevalent among many species, including humans. Both rats and mice use ultrasonic vocalizations (USVs) in various social contexts and affective states. The motor cortex is hypothesized to be involved in precisely controlling USVs through connections with critical regions of the brain for vocalization, such as the periaqueductal gray matter (PAG). However, it is unclear how neurons in the motor cortex are modulated during USVs. Moreover, the relationship between USV modulation of neurons and anatomical connections from the motor cortex to PAG is also not clearly understood. In this study, we first characterized the activity patterns of neurons in the primary and secondary motor cortices during emission of USVs in rats using large-scale electrophysiological recordings. We also examined the axonal projection of the motor cortex to PAG using retrograde labeling and identified two clusters of PAG-projecting neurons in the anterior and posterior parts of the motor cortex. The neural activity patterns around the emission of USVs differed between the anterior and posterior regions, which were divided based on the distribution of PAG-projecting neurons in the motor cortex. Furthermore, using optogenetic tagging, we recorded the USV modulation of PAG-projecting neurons in the posterior part of the motor cortex and found that they showed predominantly sustained excitatory responses during USVs. These results contribute to our understanding of the involvement of the motor cortex in the generation of USV at the neuronal and circuit levels.

Motion in the visual scene is processed by direction-selective neurons in primary visual cortex. These cells receive inputs that differ in space and time. What are these inputs? A previous single-unit recording study in anesthetized monkey V1 proposed that the two major streams arising in the primate retina, the M and P pathways, differed in space and time as required to create direction selectivity. We confirmed that cortical cells driven by P inputs tend to have sustained responses. The M pathway, however, as assessed by recordings in layer 4Cα and from cells with high contrast sensitivity, is not purely transient. The diversity of timing in the M stream suggests that combinations of M inputs, as well as of M and P inputs, create direction selectivity.

A decreased motor response after repeated doses of apomorphine is observed in severely affected Parkinson's disease patients. We simultaneously studied clinical symptoms and internal pallidus single unit activity in three parkinsonian patients underlying stereotaxic neurosurgery for deep brain stimulation. In each patient, two closely spaced doses of intraoperatory apomorphine were administered, while recording the same extracellular unit. The reduced clinical effect of the second administration was correlated to a lessened inhibition of the pallidal single unit recorded throughout the double administration. Our data support the proposition that fast postsynaptic desensitization to dopamine agonists may take place in the basal ganglia nuclei and play a role in the physiopathology of levodopa long-term treatment syndrome. 1999 Academic Press

The aim of this study was to quantify the distribution of microvessels and mast cells in all three parts of the trigeminal ganglion (TG). Statistical analyses were applied to investigate possible micromorphological regional differences in their density. Five serially sectioned human TGs were prepared for CD34 and mast cell tryptase immunostaining. The following quantifications were performed in microscopic fields of three parts of the TG: microvessel density (MVD), mast cell density (MCD) and ganglionic cell count. The density of CD34-positive microvessels was not significantly different in any of the three observed parts of the TG. The distribution of neurons showed no significant statistical difference in three parts of the TG. There was no difference in the density of tryptase-positive mast cells within the TG, but there was an abundant presence of mast cells in the periganglionic dural and subdural tissues, a finding hitherto not reported. We can say that there is a homogenous vascular pattern within the TG which excludes local predominance in pathogenesis of trigeminal neuralgia. Second, and more important, the finding of peri-trigeminal mast cells indicates their important role in migraine pain and confirms their degranulation as the main therapeutic goal for this condition.

The aim of this study was to quantify the distribution of microvessels and mast cells in all three parts of the trigeminal ganglion (TG). Statistical analyses were applied to investigate possible micromorphological regional differences in their density. Five serially sectioned human TGs were prepared for CD34 and mast cell tryptase immunostaining. The following quantifications were performed in microscopic fields of three parts of the TG: microvessel density (MVD), mast cell density (MCD) and ganglionic cell count. The density of CD34-positive microvessels was not significantly different in any of the three observed parts of the TG. The distribution of neurons showed no significant statistical difference in three parts of the TG. There was no difference in the density of tryptase-positive mast cells within the TG, but there was an abundant presence of mast cells in the periganglionic dural and subdural tissues, a finding hitherto not reported. We can say that there is a homogenous v...

Ultrasound as a widely used imaging means for medical diagnosis has drawn growing interests as a potential noninvasive neuromodulation strategy. Focused pulsed ultrasound effectively modulates neural encoding and transmission functions especially in the peripheral nervous system (PNS) with unclear mechanism of action, which is further confounded by contradictory experimental outcomes. Lack of convincing experimental methods has hindered our mechanistic understanding of ultrasonic PNS neuromodulation. To address that, we developed a novel in vitro set up to achieve simultaneous single-unit recordings from individual mouse sciatic nerve axon and systematically studied the effect of focused pulsed ultrasound (FPUS) on action potential transmission in individual axons. Unlike previous results that were derived from bulk recordings of compound action potentials (CAP) or evoked muscle forces, our singleunit recordings afford superior spatial and temporal resolution to reveal the subtle bu...

Electrophysiological techniques and in vivo microdialysis were used to investigate the effect of SB 242 084, a potent and selective 5-HT 2C receptor antagonist in the control of nigro-striatal and mesolimbic dopaminergic function. Thus, extracellular single unit recordings were performed from neurochemically-identified dopamine (DA) neurons in the substantia nigra, pars compacta (SNc) and the ventral tegmental area (VTA), as well as monitoring of striatal and accumbal basal DA release in anesthetized rats following the administration of SB 242 084 and RO 60-0175. Administration of SB 242 084 (160-640 mg/kg, i.v.) caused a dose-dependent increase in the basal firing rate of VTA DA neurons, reaching its maximum (27.8 9 6%, above baseline) after 640 mg/kg. Moreover, bursting activity was significantly enhanced by SB 242 084 in the VTA. On the other hand, SB 242 084 (160-640 mg/kg, i.v.) did not cause any significant change in the basal firing rate and bursting activity of DA neurons in the SNc. Injection of the 5-HT 2C receptor agonist RO 60-0175 (80-320% mg/kg, i.v.) dose-dependently decreased the basal firing of DA neurons in the VTA but not in the SNc. RO 60-0175 exerted its maximal inhibitory effect (53.9 915.1%, below baseline) in the VTA at the dose of 320 mg/kg. Basal DA release (34.8 99%, above baseline) and dihydroxyphenylacetic acid (DOPAC) efflux (19.7 97%, above baseline) were significantly enhanced in the nucleus accumbens following the intraperitoneal administration of 10 mg/kg SB 242 084. Intraperitoneal injection of 5 mg/kg SB 242 084 significantly increased DA release (16.4 9 6%, above baseline) in the nucleus accumbens, but did not affect DOPAC efflux. In the striatum, SB 242 084 (5 and 10 mg/kg, i.p.) only slightly increased DA release above baseline (3.5 94 and 11.2 9 6%, respectively), without affecting DOPAC efflux in this area. However, the effect of SB 242 084 in the striatum was rendered more evident by the fact that injection of the vehicle used to dissolve the drug in a group of control rats, significantly reduced basal DA output by 19.69 7%. Stimulation of 5-HT 2C receptors by RO 60-0175 (1 mg/kg, i.p.) significantly decreased DA release in the nucleus accumbens by 26.1 9 4% (below baseline) 60 min after injection. On the other hand, RO 60-0175 (1 mg/kg, i.p.) did not cause any significant change of DA release in the striatum. However, DOPAC efflux was reduced by RO 60-0175 (1 mg/kg, i.p.) both in the striatum and the nucleus accumbens. Taken together, these data indicate that the central 5-HT system exerts a tonic and phasic inhibitory control on mesolimbic DA neuron activity and that 5-HT 2C receptor subtypes are involved in this effect. Moreover, these findings might open new possibilities for the employment of 5-HT 2C receptor antagonists in the treatment of neuropsychiatric disorders related to a hypofunction of central DA neurons.

Electrophysiological techniques and in vivo microdialysis were used to investigate the effect of SB 242 084, a potent and selective 5-HT 2C receptor antagonist in the control of nigro-striatal and mesolimbic dopaminergic function. Thus, extracellular single unit recordings were performed from neurochemically-identified dopamine (DA) neurons in the substantia nigra, pars compacta (SNc) and the ventral tegmental area (VTA), as well as monitoring of striatal and accumbal basal DA release in anesthetized rats following the administration of SB 242 084 and RO 60-0175. Administration of SB 242 084 (160-640 mg/kg, i.v.) caused a dose-dependent increase in the basal firing rate of VTA DA neurons, reaching its maximum (27.8 9 6%, above baseline) after 640 mg/kg. Moreover, bursting activity was significantly enhanced by SB 242 084 in the VTA. On the other hand, SB 242 084 (160-640 mg/kg, i.v.) did not cause any significant change in the basal firing rate and bursting activity of DA neurons in the SNc. Injection of the 5-HT 2C receptor agonist RO 60-0175 (80-320% mg/kg, i.v.) dose-dependently decreased the basal firing of DA neurons in the VTA but not in the SNc. RO 60-0175 exerted its maximal inhibitory effect (53.9 915.1%, below baseline) in the VTA at the dose of 320 mg/kg. Basal DA release (34.8 99%, above baseline) and dihydroxyphenylacetic acid (DOPAC) efflux (19.7 97%, above baseline) were significantly enhanced in the nucleus accumbens following the intraperitoneal administration of 10 mg/kg SB 242 084. Intraperitoneal injection of 5 mg/kg SB 242 084 significantly increased DA release (16.4 9 6%, above baseline) in the nucleus accumbens, but did not affect DOPAC efflux. In the striatum, SB 242 084 (5 and 10 mg/kg, i.p.) only slightly increased DA release above baseline (3.5 94 and 11.2 9 6%, respectively), without affecting DOPAC efflux in this area. However, the effect of SB 242 084 in the striatum was rendered more evident by the fact that injection of the vehicle used to dissolve the drug in a group of control rats, significantly reduced basal DA output by 19.69 7%. Stimulation of 5-HT 2C receptors by RO 60-0175 (1 mg/kg, i.p.) significantly decreased DA release in the nucleus accumbens by 26.1 9 4% (below baseline) 60 min after injection. On the other hand, RO 60-0175 (1 mg/kg, i.p.) did not cause any significant change of DA release in the striatum. However, DOPAC efflux was reduced by RO 60-0175 (1 mg/kg, i.p.) both in the striatum and the nucleus accumbens. Taken together, these data indicate that the central 5-HT system exerts a tonic and phasic inhibitory control on mesolimbic DA neuron activity and that 5-HT 2C receptor subtypes are involved in this effect. Moreover, these findings might open new possibilities for the employment of 5-HT 2C receptor antagonists in the treatment of neuropsychiatric disorders related to a hypofunction of central DA neurons.

We have previously shown that most cells in the alert monkey V1 are complex cells with overlapping increment and decrement activating regions and nonlinear response properties. Diverse responses of these cells to drifting gratings differ from the unmodulated firing usually ascribed to complex cells, and cannot be predicted from receptive field spatial maps. We recorded extracellular responses in V1 of macaques performing a fixation task, while systematically varying spatial and temporal frequency and width of the grating patch. ...

Multi- and single-unit recording was performed in the gracile nucleus in urethane-anesthetized rats to examine estrous variations in responses of its neurons to brushing the hindquarters and mechanical stimulation of the uterus, vaginal canal, cervix, and colon. Six rats each were studied in each of the four estrous stages: proestrus (P), estrus (E), metestrus (M), and diestrus (D). The magnitude of multi-unit responses to gentle brushing of the perineum, hip, and tail, but not the foot and leg, was significantly greater during proestrus than during other stages. Of 70 single units responsive to brush, 56 (80%) responded to stimulation of at least one viscus. Although this percentage did not change with estrous stage, the direction and latency of some responses did. Pressure on the cervix evoked significantly more inhibitory (vs excitatory) responses in P than in E and M, and the response latency was significantly longer in D and P than in E and M. The direction of response to vagin...

The pontine storage centre (PSC) and the pontine micturition centre (PMC) are known to be critical for urinary filling and emptying, respectively. In the present study, firing patterns of 45 neurons in the PSC area where electrical stimulation induced inhibition of the micturition reflex were analyzed in 20 male decerebrated and paralyzed cats. The electrically determined PSC area was widespread in the dorsolateral pontine reticular formation (P0-P4), ventrolateral to the PMC. Four major types of neurons were detected according to urinary storage/micturition cycles: tonic storage neurons (38%), phasic storage neurons (40%), tonic micturition neurons (9%) and phasic micturition neurons (13%). These four types of neurons were intermingled in the PSC. However, the tonic and phasic micturition neurons tended to be located within a limited area (P2-P3). These neurons were further classified into augmenting, constant and decrementing firing patterns. Some increased their firing prior to the storage/micturition phase initiation. Such preceding pattern was more frequently found in the tonic neurons than in the phasic neurons. In conclusion, the PSC neurons with diverse heterogeneous discharge patterns suggest that these neurons may organize a complex neuronal circuitry, which is critical in the neural control of the urinary continence.

The dopaminergic neurons and cholinergic interneurons of the striatum play key roles in motivational and sensorimotor processing by the basal ganglia. The striatal dopaminergic transmission in the forebrain is modulated by the excitatory cholinergic projections from the pedunculopontine and the laterodorsal tegmental nuclei of the hind brain by activating nicotinic and muscarinic acetylcholine receptors within the substantia nigra and ventral tegmental area. Furthermore, acetylcholine-containing interneurons in the striatum also constitute an important neural substrate for modulating dopamine activity. The striatal muscarinic acetylcholine receptors, by inhibiting acetylcholine release from cholinergic interneurons and thus modifying nicotinic acetylcholine receptor activity, offer variable control of dopamine release probability. In addition, it appears that the striatal influence of dopamine and acetylcholine cannot be fully appreciated without an understanding of their reciprocal interactions. Impairments or abnormality in these reciprocating interactions is often manifested in the form of various neuropsychiatric disorders and require extensive research to establish the optimized drug therapy. Hence the present review will serve as an aid to study the anatomical and physiological aspects of dopamine modulation as influenced by acetylcholine in striatum.