Papers by Daniela Carulli
Following axotomy, cerebellar Purkinje cells (PCs) do not elongate their axons, even in a favoura... more Following axotomy, cerebellar Purkinje cells (PCs) do not elongate their axons, even in a favourable environment, and are resistant to death. They have no constitutive presence of common growth-associated proteins, such as GAP-43 and c-Jun Previous experiments show that injured transgenic PCs overexpressing GAP-43 exhibit a profuse sprouting along the axon and at its severed end. Nevertheless, the lesioned axons are unable to regenerate either spontaneously or into growth-permissive environments. In addition, a considerable number of GAP-43 transgenic PCs degenerate after injury. c-Jun is an inducible transcription factor expressed in axotomized central neurons and regenerating peripheral neurons. It also contributes to programmed cell death during development. To test whether c-Jun could modify the response of PCs to axotomy or enhance the growth/death phenomena of GAP-43 Purkinje neurons, we generated transgenic mice overexpressing c-Jun in PCs. However, c-Jun upregulation did not affect the adult intact phenotype of these neurons and their regenerative and survival capabilities after axotomy. Also in the cross-bred GAP-43/c-Jun mice, c-Jun did not modify the response of GAP-43 PCs to axotomy. By contrast, in organotypic cultures of cerebellum taken from 9-day-old-pups, the survival capabilities of PCs overexpressing c-Jun decreased, in association with a consistent c-Jun phosphorylation. On the whole our data show that c-Jun alone is unable to trigger regenerative or degenerative phenomena in PCs and suggest that the cellular action of this early gene in developing and mature neurons strongly depends on interplaying intracellular signals.
Neuroscience, 2003
Pattern of activity during development is important for the refinement of the final architecture ... more Pattern of activity during development is important for the refinement of the final architecture of the brain. In the cerebellar cortex, the regression from multiple to single climbing fiber innervation of the Purkinje cell occurs during development between postnatal days (P) 5 and 15. However, the regression is hampered by altering in various ways the morpho-functional integrity of the parallel fiber input. In rats we disrupted the normal activity pattern of the climbing fiber, the terminal arbor of the inferior olive neurons, by administering harmaline for 4 days from P9 to P12. At all studied ages (P15-87) after harmaline treatment multiple (double only) climbing fiber EPSC-steps persist in 28% of cells as compared with none in the control. The ratio between the amplitudes of the larger and the smaller climbing fiber-evoked EPSC increases in parallel with the decline of the polyinnervation factor, indicating a gradual enlargement of the synaptic contribution of the winning climbing fiber synapse at the expense of the losing one. Harmaline treatment had no later effects on the climbing fiber EPSC kinetics and I/V relation in Purkinje cells (P15-36). However, there was a rise in the paired-pulse depression indicating a potentiation of the presynaptic mechanisms. In the same period, after harmaline treatment, parallel fiber-Purkinje cell electrophysiology was unaffected. The distribution of parallel fiber synaptic boutons was also not changed. Thus, a change in the pattern of activity during a narrow developmental period may affect climbing fiber-Purkinje cell synapse competition resulting in occurrence of multiple innervation at least up to 3 months of age. Our results extend the current view on the role of the pattern of activity in the refinement of neuronal connections during development. They suggest that many similar results obtained by different gene or receptor manipulations might be simply the consequence of disrupting the pattern of activity.
Frontiers in Molecular Neuroscience, 2011
Information processing, memory formation, or functional recovery after nervous system damage depe... more Information processing, memory formation, or functional recovery after nervous system damage depend on the ability of neurons to modify their functional properties or their connections. At the cellular/molecular level, structural modifications of neural circuits are finely regulated by intrinsic neuronal properties and growth-regulatory cues in the extracellular milieu. Recently, it has become clear that stimuli coming from the external world, which comprise sensory inflow, motor activity, cognitive elaboration, or social interaction, not only provide the involved neurons with instructive information needed to shape connection patterns to sustain adaptive function, but also exert a powerful influence on intrinsic and extrinsic growth-related mechanisms, so to create permissive conditions for neuritic remodeling. Here, we present an overview of recent findings concerning the effects of experience on molecular mechanisms underlying CNS structural plasticity, both in physiological conditions and after damage, with particular focus on activity-dependent modulation of growth-regulatory genes and epigenetic modifications.
Progress in Neurobiology, 2004
In the adult brain, different neuronal populations display different degrees of plasticity. Here,... more In the adult brain, different neuronal populations display different degrees of plasticity. Here, we describe the highly different plastic properties of inferior olivary neurones and Purkinje cells. Olivary neurones show a basal expression of growth-associated proteins, such as GAP-43 and Krox24/EGR-1, and remarkable remodelling capabilities of their terminal arbour. They also regenerate their transected neurites into growth-permissive territories and may reinnervate the lost target. Sprouting and regrowing olivary axons are able to follow specific positional information cues to establish new connections according to the original projection map. In addition, they set a strong cell body reaction to injury, which in specific olivary subsets is regulated by inhibitory target-derived cues. In contrast, Purkinje cells do not have a constitutive level of growth-associated genes, and show little cell body reaction, no axonal regeneration after axotomy, and weak sprouting capabilities. Block of myelin-derived signals allows terminal arbour remodelling, but not regeneration, while selective over-expression of GAP-43 induces axonal sprouting along the axonal surface and at the level of the lesion. We suggest that the high constitutive intrinsic plasticity of the inferior olive neurones allows their terminal arbour to sustain the activity-dependent ongoing competition with the parallel fibres in order to maintain the post-synaptic territory, and possibly underlies mechanisms of learning and memory. Such a plasticity is used also as a reparative mechanism following axotomy. In contrast, in Purkinje cells, poor intrinsic regenerative capabilities and myelin-derived signals stabilise the mature connectivity and prevent axonal regeneration after lesion.
PLoS ONE, 2011
Structural remodeling or repair of neural circuits depends on the balance between intrinsic neuro... more Structural remodeling or repair of neural circuits depends on the balance between intrinsic neuronal properties and regulatory cues present in the surrounding microenvironment. These processes are also influenced by experience, but it is still unclear how external stimuli modulate growth-regulatory mechanisms in the central nervous system. We asked whether environmental stimulation promotes neuronal plasticity by modifying the expression of growth-inhibitory molecules, specifically those of the extracellular matrix. We examined the effects of an enriched environment on neuritic remodeling and modulation of perineuronal nets in the deep cerebellar nuclei of adult mice. Perineuronal nets are meshworks of extracellular matrix that enwrap the neuronal perikaryon and restrict plasticity in the adult CNS. We found that exposure to an enriched environment induces significant morphological changes of Purkinje and precerebellar axon terminals in the cerebellar nuclei, accompanied by a conspicuous reduction of perineuronal nets. In the animals reared in an enriched environment, cerebellar nuclear neurons show decreased expression of mRNAs coding for key matrix components (as shown by real time PCR experiments), and enhanced activity of matrix degrading enzymes (matrix metalloproteinases 2 and 9), which was assessed by in situ zymography. Accordingly, we found that in mutant mice lacking a crucial perineuronal net component, cartilage link protein 1, perineuronal nets around cerebellar neurons are disrupted and plasticity of Purkinje cell terminal is enhanced. Moreover, all the effects of environmental stimulation are amplified if the afferent Purkinje axons are endowed with enhanced intrinsic growth capabilities, induced by overexpression of GAP-43. Our observations show that the maintenance and growth-inhibitory function of perineuronal nets are regulated by a dynamic interplay between preand postsynaptic neurons. External stimuli act on this interaction and shift the balance between synthesis and removal of matrix components in order to facilitate neuritic growth by locally dampening the activity of inhibitory cues.
Journal of Neurochemistry, 2010
We have previously shown that all perineuronal nets (PNNs) bearing neurons express a hyaluronan s... more We have previously shown that all perineuronal nets (PNNs) bearing neurons express a hyaluronan synthase (HAS), a link protein (usually cartilage link protein-1; Crtl1) and a chondroitin sulfate proteoglycan (usually aggrecan). Animal lacking Crtl1 in the CNS lacks normal PNNs. PNNs are implicated in the control of neuronal plasticity, and interventions to modulate PNN formation will be useful for manipulating plasticity. We have developed an in vitro model which demonstrates how the structural components of PNNs trigger their formation, using human embryonic kidney cells, which do not normally produce a pericellular matrix. Expression of HAS3 leads to the production of a diffuse matrix. It was converted into a compact PNN-like structure when the cells also expressed Crtl1 and aggrecan. This matrix was stained by Wisteria floribunda, contained Crtl1 and aggrecan, and like PNNs, could only be solubilized in 6 M urea. In the absence of hyaluronan produced by HAS3, aggrecan and Crtl1 dissipated into the medium, but when the cells were transfected to produce a hyaluronan matrix, Crtl1 and aggrecan were incorporated into it. Cells lacking any one of these molecules showed impaired integrity of the PNNs. Cells expressing HAS3 and Crtl1 were able to incorporate exogenous aggrecan into their pericellular matrix.
Upregulation of aggrecan, link protein 1, and hyaluronan synthases during formation of perineuronal nets in the rat cerebellum
The Journal of Comparative Neurology, 2007
Extracellular matrix molecules accumulate around central nervous system neurons during postnatal ... more Extracellular matrix molecules accumulate around central nervous system neurons during postnatal development, forming so-called perineuronal nets (PNNs). PNNs play a role in restricting plasticity at the end of critical periods. In the adult rat cerebellum, PNNs are found around large, deep cerebellar nuclei (DCN) neurons and Golgi neurons and are composed of chondroitin sulfate proteoglycans (CSPGs), tenascin-R (TN-R), hyaluronan (HA), and link proteins, such as cartilage link protein 1 (Crtll). Granule cells and Purkinje cells are surrounded by a partially organized matrix. Both glial cells and neurons surrounded by PNNs are the site of synthesis of some CSPGs and of TN-R, but only neurons produce HA synthetic enzymes (HASs), thus HA, and link proteins, which are scaffolding molecules for an organized matrix. To elucidate the mechanisms of formation of PNNs, we analyzed by immunohistochemistry and in situ hybridization which PNN components are upregulated during PNN formation in rat cerebellar postnatal development and what cell types express them. We observed that Wisteria floribunda agglutinin-binding PNNs develop around DCN neurons from postnatal day (P)7 and around Golgi neurons from P14. At the same time as their PNNs start to form, these neurons upregulate aggrecan, Crtll, and HASs mRNAs. However, Crtll is the only PNN component to be expressed exclusively in neurons surrounded by PNNs. The other link protein that shows a perineuronal net pattern in the DCN, Bral2, is upregulated later during development. These data suggest that aggrecan, HA, and, particularly, Crtll might be crucial elements for the initial assembly of PNNs.
The Journal of comparative neurology, 2006
The decrease in plasticity that occurs in the central nervous system during postnatal development... more The decrease in plasticity that occurs in the central nervous system during postnatal development is accompanied by the appearance of perineuronal nets (PNNs) around the cell body and dendrites of many classes of neuron. These structures are composed of extracellular matrix molecules, such as chondroitin sulfate proteoglycans (CSPGs), hyaluronan (HA), tenascin-R, and link proteins. To elucidate the role played by neurons and glial cells in constructing PNNs, we studied the expression of PNN components in the adult rat cerebellum by immunohistochemistry and in situ hybridization. In the deep cerebellar nuclei, only large excitatory neurons were surrounded by nets, which contained the CSPGs aggrecan, neurocan, brevican, versican, and phosphacan, along with tenascin-R and HA. Whereas both net-bearing neurons and glial cells were the sources of CSPGs and tenascin-R, only the neurons expressed the mRNA for HA synthases (HASs), cartilage link protein, and link protein Bral2. In the cerebe...
European Journal of Neuroscience, 2003
Successful axon regeneration relies on the capability of the lesioned neurons to up-regulate a sp... more Successful axon regeneration relies on the capability of the lesioned neurons to up-regulate a speci®c set of injury/growth-associated genes. In the adult central nervous system, the strength of the cell body response is generally related to the distance of the injury site from the perikaryon, being stronger for proximal lesions. Nevertheless, inferior olive (IO) cells react to injury and regenerate their axons even after distal transections. To investigate the mechanisms that regulate the IO growth properties, we examined the expression of injury/growth markers (nitric oxide synthase, growth-associated protein 43 and c-Jun) after target deletion or axotomy performed at different sites along the olivocerebellar pathway. Both axon injury and target loss disclose two subsets of IO neurons distributed within precise subnuclei: one subset up-regulates all markers in all conditions, whereas the other shows a mild c-Jun expression but remains unresponsive even after a very proximal axotomy. These observations indicate that distinct subpopulations of IO cells respond to different regulatory strategies. Unresponsive neurons appear insensitive to environmental positive or negative cues, suggesting that they are intrinsically unable to set up a cellular reaction to injury. In contrast, cell body changes in reactive neurons are elicited after the removal of retrogradely transported target-derived inhibitory signals. Target loss also induces degeneration of IO cells, whose survival remains partially dependent on Purkinje targets in adulthood. Thus, the intrinsic regenerative potential of a functionally homogeneous population is regulated by multiple mechanisms, speci®c for distinct neuronal subsets.
Overexpression of GAP-43 modifies the distribution of the receptors for myelin-associated growth-inhibitory proteins in injured Purkinje axons
European Journal of Neuroscience, 2009
Abstract Neurons with enhanced intrinsic growth capabilities can elongate their axons into non-pe... more Abstract Neurons with enhanced intrinsic growth capabilities can elongate their axons into non-permissive territories, but the mechanisms that enable the outgrowing processes to overcome environmental inhibition are largely unknown. To address this issue, we examined adult mouse Purkinje cells that overexpress the axonal growth-associated protein GAP-43. After injury, these neurons exhibit sprouting along the intracortical neuritic course and at the severed stump in the white matter. To determine whether GAP-43-overexpressing Purkinje cells are responsive to extrinsic inhibitory cues, we investigated the content and subcellular localization of major receptors for myelin-associated inhibitory proteins, PlexinB1 and the Nogo receptor (NgR) with the related co-receptors LINGO-1 and p75. Expression of these molecules, estimated by measuring perikaryal immunostaining intensity and Western blot, was not different in wild-type or transgenic mice, and it was not overtly modified after axotomy. Following injury, however, the content of PlexinB1 was significantly reduced in GAP-43-overexpressing neurites. Furthermore, in the same axons the distribution of both PlexinB1 and NgR was altered, being inverse to that of GAP-43. Labelling for the two receptors was conspicuously reduced on the axonal surface and it was almost undetectable in the outgrowing sprouts, which showed strong GAP-43 immunoreactivity. These observations indicate that although GAP-43 overexpression does not modify the expression of receptors for myelin-associated inhibitory factors, it interferes with their subcellular localization and exposure on the neuritic membrane. Therefore, GAP-43 promotes axon growth by multiple synergistic mechanisms that potentiate the intrinsic motility of the elongating processes, while reducing their sensitivity to environmental inhibition.
European Journal of Neuroscience, 2008
Perineuronal nets (PNNs) are dense extracellular matrix (ECM) structures that form around many ne... more Perineuronal nets (PNNs) are dense extracellular matrix (ECM) structures that form around many neuronal cell bodies and dendrites late in development. They contain several chondroitin sulphate proteoglycans (CSPGs), hyaluronan, link proteins and tenascin-R. Their time of appearance correlates with the ending of the critical period for plasticity, and they have been implicated in this process. The distribution of PNNs in the spinal cord was examined using Wisteria floribunda agglutinin lectin and staining for chondroitin sulphate stubs after chondroitinase digestion. Double labelling with the neuronal marker, NeuN, showed that PNNs were present surrounding 30% of motoneurons in the ventral horn, 50% of large interneurons in the intermediate grey and 20% of neurons in the dorsal horn. These PNNs formed in the second week of postnatal development. Immunohistochemical staining demonstrated that the PNNs contain a mixture of CSPGs, hyaluronan, link proteins and tenascin-R. Of the CSPGs, aggrecan was present in all PNNs while neurocan, versican and phosphacan ⁄ RPTPb were present in some but not all PNNs. In situ hybridization showed that aggrecan and cartilage link protein (CRTL 1) and brain link protein-2 (BRAL 2) are produced by neurons. PNN-bearing neurons express hyaluronan synthase, and this enzyme and phosphacan ⁄ RPTPb may attach PNNs to the cell surface. During postnatal development the expression of link protein and aggrecan mRNA is up-regulated at the time of PNN formation, and these molecules may therefore trigger their formation.
European Journal of Neuroscience, 2002
Following axotomy, cerebellar Purkinje cells (PCs) do not elongate their axons, even in a favoura... more Following axotomy, cerebellar Purkinje cells (PCs) do not elongate their axons, even in a favourable environment, and are resistant to death. They have no constitutive presence of common growth-associated proteins, such as GAP-43 and c-Jun Previous experiments show that injured transgenic PCs overexpressing GAP-43 exhibit a profuse sprouting along the axon and at its severed end. Nevertheless, the lesioned axons are unable to regenerate either spontaneously or into growth-permissive environments. In addition, a considerable number of GAP-43 transgenic PCs degenerate after injury. c-Jun is an inducible transcription factor expressed in axotomized central neurons and regenerating peripheral neurons. It also contributes to programmed cell death during development. To test whether c-Jun could modify the response of PCs to axotomy or enhance the growth/death phenomena of GAP-43 Purkinje neurons, we generated transgenic mice overexpressing c-Jun in PCs. However, c-Jun upregulation did not affect the adult intact phenotype of these neurons and their regenerative and survival capabilities after axotomy. Also in the cross-bred GAP-43/c-Jun mice, c-Jun did not modify the response of GAP-43 PCs to axotomy. By contrast, in organotypic cultures of cerebellum taken from 9-day-old-pups, the survival capabilities of PCs overexpressing c-Jun decreased, in association with a consistent c-Jun phosphorylation. On the whole our data show that c-Jun alone is unable to trigger regenerative or degenerative phenomena in PCs and suggest that the cellular action of this early gene in developing and mature neurons strongly depends on interplaying intracellular signals.
Chondroitin 6-sulphate synthesis is up-regulated in injured CNS, induced by injury-related cytokines and enhanced in axon-growth inhibitory glia
European Journal of Neuroscience, 2005
Chondroitin sulphate proteoglycans (CSPGs) are up-regulated in the CNS after injury and inhibit a... more Chondroitin sulphate proteoglycans (CSPGs) are up-regulated in the CNS after injury and inhibit axon regeneration mainly through their glycosaminoglycan (CS-GAG) chains. We have analysed the mRNA levels of the CS-GAG synthesizing enzymes and measured the CS-GAG disaccharide composition by chromatography and immunocytochemistry. Chondroitin 6-sulfotransferase 1 (C6ST1) is up-regulated in most glial types around cortical injuries, and its sulphated product CS-C is also selectively up-regulated. Treatment with TGFalpha and TGFbeta, which are released after brain injury, promotes the expression of C6ST1 and the synthesis of 6-sulphated CS-GAGs in primary astrocytes. Oligodendrocytes, oligodendrocyte precursors and meningeal cells are all inhibitory to axon regeneration, and all express high levels of CS-GAG, including high levels of 6-sulphated GAG. In axon growth-inhibitory Neu7 astrocytes C6ST1 and 6-sulphated GAGs are expressed at high levels, whereas in permissive A7 astrocytes they are not detectable. These results suggest that the up-regulation of CSPG after CNS injury is associated with a specific sulphation pattern on CS-GAGs, mediating the inhibitory properties of proteoglycans on axonal regeneration.
Current Opinion in Neurobiology, 2005
Cell and Tissue Research, 2012
During developmental critical periods, external stimuli are crucial for information processing, a... more During developmental critical periods, external stimuli are crucial for information processing, acquisition of new functions or functional recovery after CNS damage. These phenomena depend on the capability of neurons to modify their functional properties and/or their connections, generally defined as "plasticity". Although plasticity decreases after the closure of critical periods, the adult CNS retains significant capabilities for structural remodelling and functional adaptation. At the molecular level, structural modifications of neural circuits depend on the balance between intrinsic growth properties of the involved neurons and growth-regulatory cues of the extracellular milieu. Interestingly, experience acts on this balance, so as to create permissive conditions for neuritic remodelling. Here, we present an overview of recent findings concerning the effects of experience on cellular and molecular processes responsible for producing structural plasticity of neural networks or functional recovery after an insult to the adult CNS (e.g. traumatic injury, ischemia or neurodegenerative disease). Understanding experience-dependent mechanisms is crucial for the development of tailored rehabilitative strategies, which can be exploited alone or in combination with specific therapeutic interventions to improve neural repair after damage.
Animals lacking link protein have attenuated perineuronal nets and persistent plasticity
Brain, 2010
Chondroitin sulphate proteoglycans in the extracellular matrix restrict plasticity in the adult c... more Chondroitin sulphate proteoglycans in the extracellular matrix restrict plasticity in the adult central nervous system and their digestion with chondroitinase reactivates plasticity. However the structures in the extracellular matrix that restrict plasticity are unknown. There are many changes in the extracellular matrix as critical periods for plasticity close, including changes in chondroitin sulphate proteoglycan core protein levels, changes in glycosaminoglycan sulphation and the appearance of dense chondroitin sulphate proteoglycan-containing perineuronal nets around many neurons. We show that formation of perineuronal nets is triggered by neuronal production of cartilage link protein Crtl1 (Hapln1), which is up-regulated in the visual cortex as perineuronal nets form during development and after dark rearing. Mice lacking Crtl1 have attenuated perineuronal nets, but the overall levels of chondroitin sulphate proteoglycans and their pattern of glycan sulphation are unchanged. Crtl1 knockout animals retain juvenile levels of ocular dominance plasticity and their visual acuity remains sensitive to visual deprivation. In the sensory pathway, axons in knockout animals but not controls sprout into the party denervated cuneate nucleus. The organization of chondroitin sulphate proteoglycan into perineuronal nets is therefore the key event in the control of central nervous system plasticity by the extracellular matrix.
Annals of the New York Academy of Sciences, 2007
spine formation. Coincidentally, the olivary terminals belonging to the few survived olivary neur... more spine formation. Coincidentally, the olivary terminals belonging to the few survived olivary neurons undergo an extensive collateral sprouting resulting in reinnervation of the neighboring denervated PCs. We obtained chemical deafferentation of PCs in adult rats (body weight, 120-170 g; age, 35-40 days) by a single intraperitoneal injection of 3AP (65 mg/kg body weight), and as early as 3 days after 3AP treatment, important morphological changes could be observed on PCs.MAPK (mitogenactivated protein kinase) cascades and more specifically extracellular signal-regulated kinases 1/2 (ERK1/2) play a critical role in the signaling events underlying synaptic plasticity. For instance, long-term depression (LTD) in the adult hippocampus and long-term potentiation (LTP) in cerebellum both involve ERK activation. Since PCs deprived of their climbing fibers (CF) afferents initiate an intensive remodeling Q1 of the spines and rapid recall of the remaining CFs, it prompted us to see whether the observed phenomena correlated with MAPK and Akt activation.Immunohistochemistry and Western blotting were done at various time points after 3AP application (from 24 h to 6 days), as the exact dynamics of CF loss is not precisely known. As judged by Western blotting, there was no increase of activated ERK in the cerebellum. However, immunohistochemistry revealed increased ERK phosphorylation in the "pinceaux" of basket cells in 3AP animals. Similarly, stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK), p38 MAPK, and Akt activation were also studied by means of Western :1156 2 ANNALS NEW YORK ACADEMY OF SCIENCES blotting and immunohistochemistry. Upon 3AP treatment no changes in phosphorylation status could be seen in the different kinases subjected to analysis. Our results suggest that activation of MAPK and Akt cascades is not essential in this model of neuronal plasticity.
Annals of the New York Academy of Sciences, 2005
The mitogen-activated protein kinases (MAPKs) are a family of signal transduction mediators that ... more The mitogen-activated protein kinases (MAPKs) are a family of signal transduction mediators that regulate a number of cellular activities, including cell growth and proliferation, differentiation and survival, via phosphorylation (activation) of protein kinases. MAPKs are also recruited during synaptic plasticity and remodeling. In the present study we used Western blotting and immunohistochemistry to examine the effects of harmaline administration on the phosphorylation state of three MAPKs: the extracellular signalregulated kinase (ERK1/2), c-Jun-N-terminal kinase/stress-activated protein kinase (JNK/SAPK), and p38 MAPK. Harmaline is a tremorigenic drug known to induce enhanced and rhythmic firing of the inferior olive. In rats, synchronous activity of the inferior olive cells induced by harmaline administered for four days from postnatal day 9 to 12 resulted in prolonged maintenance of polyinnervation of Purkinje cells by climbing fibers (axons of olivary cells). Immunohistochemistry showed small but sustained cytoplasmic positivity to phospho-ERK in Purkinje cells and a strong signal for phospho-ERK in the "pinceaux," terminals of the interneuronal basket cells onto Purkinje cells. A similar pattern was observed for JNK/SAPK, while no changes in p38 were noticed. Thus, it was revealed that the activation of two members of the MAPK family in these inhibitory presynaptic terminals is also one consequence of synchronous olivary input to Purkinje cells known to affect developmental plasticity.
Neural Plasticity, 2013
Stroke is a common and disabling global health-care problem, which is the third most common cause... more Stroke is a common and disabling global health-care problem, which is the third most common cause of death and one of the main causes of acquired adult disability in many countries. Rehabilitation interventions are a major component of patient care. In the last few years, brain stimulation, mirror therapy, action observation, or mental practice with motor imagery has emerged as interesting options as add-on interventions to standard physical therapies. The neural bases for poststroke recovery rely on the concept of plasticity, namely, the ability of central nervous system cells to modify their structure and function in response to external stimuli. In this review, we will discuss recent noninvasive strategies employed to enhance functional recovery in stroke patients and we will provide an overview of neural plastic events associated with rehabilitation in preclinical models of stroke.
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Papers by Daniela Carulli