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Visual cortical lesions destroy the target cells for geniculocortical fibers from a certain retinotopic region. This leads to a cortical scotoma. We have investigated the receptive fields of cells in the visual cortex before, 2 days and 2 months after focal ibotenic acid lesions in the adult cat visual cortex and have found signs of receptive field plasticity in the surroundings of the chronic but not the acute and subacute excitotoxic lesions. In the subacute state (first two days post lesion) receptive field sizes of cells at the border of the lesion were reduced in size or remained unchanged. Remapping of cortical receptive fields 2 months later revealed a number of cells with multifold enlarged receptive fields at the border of the lesion. The cells with enlarged receptive fields displayed orientation and direction selectivity like normal cells. The size increase appeared not specifically directed towards the scotoma; however, the enlarged receptive fields can reduce the extent of a cortical scotoma, since previously unresponsive regions of the visual field activate cortical cells at the border of the lesion. This late receptive field plasticity could serve as a mechanism for the filling-in of cortical scotomata observed in patients with visual cortex lesions. [ABSTRACT FROM AUTHOR]

Background: Macular degeneration of the eye is a common cause of blindness and affects 8% of the worldwide human population. In adult cats with bilateral lesions of the central retina, we explored the possibility that motion perception training can limit the associated degradation of the visual system. We evaluated how visual training affects behavioral performance and white matter structure. Recently, we proposed (Kozak et al. in Transl Vis Sci Technol 10:9, 2021) a new motion-acuity test for low vision patients, enabling full visual field functional assessment through simultaneous perception of shape and motion. Here, we integrated this test as the last step of a 10-week motion-perception training., Results: Cats were divided into three groups: retinal-lesioned only and two trained groups, retinal-lesioned trained and control trained. The behavioral data revealed that trained cats with retinal lesions were superior in motion tasks, even when the difficulty relied only on acuity. 7 T-MRI scanning was done before and after lesioning at 5 different timepoints, followed by Fixel-Based and Fractional Anisotropy Analysis. In cats with retinal lesions, training resulted in a more localized and reduced percentage decrease in Fixel-Based Analysis metrics in the dLGN, caudate nucleus and hippocampus compared to untrained cats. In motion-sensitive area V5/PMLS, the significant decreases in fiber density were equally strong in retinal-lesioned untrained and trained cats, up to 40% in both groups. The only cortical area with Fractional Anisotropy values not affected by central retinal loss was area V5/PMLS. In other visual ROIs, the Fractional Anisotropy values increased over time in the untrained retinal lesioned group, whereas they decreased in the retinal lesioned trained group and remained at a similar level as in trained controls., Conclusions: Overall, our MRI results showed a stabilizing effect of motion training applied soon after central retinal loss induction on white matter structure. We propose that introducing early motion-acuity training for low vision patients, aimed at the intact and active retinal peripheries, may facilitate brain plasticity processes toward better vision., (© 2024. The Author(s).)

Adult visual plasticity underlying local remodeling of the cortical circuitry in vivo appears to be associated with a spatiotemporal pattern of strongly increased spontaneous and evoked activity of populations of cells. Here we review and discuss pioneering work by us and others about principles of plasticity in the adult visual cortex, starting with our study which showed that a confined lesion in the cat retina causes increased excitability in the affected region in the primary visual cortex accompanied by fine-tuned restructuring of neuronal function. The underlying remodeling processes was further visualized with voltage-sensitive dye (VSD) imaging that allowed a direct tracking of retinal lesion-induced reorganization across horizontal cortical circuitries. Nowadays, application of noninvasive stimulation methods pursues the idea further of increased cortical excitability along with decreased inhibition as key factors for the induction of adult cortical plasticity. We used high-frequency transcranial magnetic stimulation (TMS), for the first time in combination with VSD optical imaging, and provided evidence that TMS-amplified excitability across large pools of neurons forms the basis for noninvasively targeting reorganization of orientation maps in the visual cortex. Our review has been compiled on the basis of these four own studies, which we discuss in the context of historical developments in the field of visual cortical plasticity and the current state of the literature. Overall, we suggest markers of LTP-like cortical changes at mesoscopic population level as a main driving force for the induction of visual plasticity in the adult. Elevations in excitability that predispose towards cortical plasticity are most likely a common property of all cortical modalities. Thus, interventions that increase cortical excitability are a promising starting point to drive perceptual and potentially motor learning in therapeutic applications., (© 2023. The Author(s).)

Purpose of the Study: Traumatic optic neuropathy (TON) is a rare but serious consequence of head injuries. The optimal therapy for TON remains controversial, and standardized recommendations are lacking. The most common therapies used are steroid administration and surgical decompression procedures. The aim of the present study was to compare two common conservative and surgical therapies in a rodent model with a standardized traumatic optic nerve lesion., Materials and Methods: This study employed 59 male Wistar rats. After exposing the optic nerve, defined trauma was exerted on the optic nerve using a micromanipulator to trigger TON. Rats received either "megadose" methylprednisolone applied perioperatively or decompression via nerve sheath fenestration. The number of neurons was histologically evaluated in retinae explanted as whole mounts. Neuronal size was determined histomorphometrically., Results: Neuronal loss was significantly lower following perioperative "megadose" steroid therapy ( p = .017), especially in the central retinal area ( p = .025). Compared to the control group without therapy, on average more than 400 neurons/mm 2 were saved. In the central retinal area, more than 600 neurons/mm 2 were rescued. In contrast, neuronal loss was not significantly affected by surgical decompression; however, this procedure was associated with a reduction in neuron size ( p = .003)., Conclusions: The present model revealed significant neuroprotective effects following administration of methylprednisolone for TON treatment. Mitigation of neuronal loss may result in functional benefits. Neuroprotective effects were not observed following surgical therapy, suggesting that this approach should be reserved for individual cases such as hematomas in the area of nerve envelopes.

The mammalian central nervous system (CNS) is characterized by a severely limited regeneration capacity. Comparison with lower species like amphibians, which are able to restore even complex tissues after damage, indicates the presence of an inhibitory environment that restricts the cellular response in mammals. In this context, signals provided by the extracellular matrix (ECM) are important regulators of events like cell survival, proliferation, migration, differentiation or neurite outgrowth. Therefore, knowledge of the post-lesional ECM and of cells that produce these factors might support development of new treatment strategies for patients suffering from traumatic brain injury and other types of CNS damage. In the present study, we analyzed the surround of focal infrared laser lesions of the adult mouse visual cortex. This lesion paradigm avoids direct contact with the brain, as the laser beam passes the intact bone. Cell type-specific markers revealed a distinct spatial distribution of different astroglial subtypes in the penumbra after injury. Glial fibrillary acidic protein (GFAP) as marker for reactive astrocytes was found broadly up-regulated, whereas the more immature markers vimentin and nestin were only expressed by a subset of cells. Dividing astrocytes could be identified via the proliferation marker Ki-67. Different ECM molecules, among others the neural stem cell-associated glycoprotein tenascin-C and the DSD-1 chondroitin sulfate epitope, were found on astrocytes in the penumbra. Wisteria floribunda agglutinin (WFA) and aggrecan as markers for perineuronal nets, a specialized ECM limiting synaptic plasticity, appeared normal in the vicinity of the necrotic lesion core. In sum, expression of progenitor markers by astrocyte subpopulations and the identification of proliferating astrocytes in combination with an ECM that contains components typically associated with neural stem/progenitor cells suggest that an immature cell fate is facilitated as response to the injury., (Copyright © 2020 Roll, Eysel and Faissner.)

Although by adulthood cortical structures and their capacity for processing sensory information have become established and stabilized, under conditions of cortical injury, or sensory deprivation, rapid reorganization occurs. Little is known as to the impact of this kind of adaptation on cellular processes related to memory encoding. However, imaging studies in humans suggest that following loss or impairment of a sensory modality, not only cortical but also subcortical structures begin to reorganize. It is likely that these processes are supported by neurotransmitter receptors that enable synaptic and cortical plasticity. Here, we explored to what extent the expression of plasticity-related proteins (GABA-A, GABA-B, GluN1, GluN2A, GluN2B) is altered following early vision loss, and whether this impacts on hippocampal function. We observed that in the period of 2-4 months postnatally in CBA/J-mice that experience hereditary postnatal retinal degeneration, systematic changes of GABA-receptor and NMDA-receptor subunit expression occurred that emerged first in the hippocampus and developed later in the cortex, compared to control mice that had normal vision. Changes were accompanied by significant impairments in hippocampal long-term potentiation and hippocampus-dependent learning. These data indicate that during cortical adaptation to early loss of vision, hippocampal information processing is compromised, and this status impacts on the acquisition of spatial representations.

Transcranial magnetic stimulation (TMS) has become a popular clinical method to modify cortical processing. The events underlying TMS-induced functional changes remain, however, largely unknown because current noninvasive recording methods lack spatiotemporal resolution or are incompatible with the strong TMS-associated electrical field. In particular, an answer to the question of how the relatively unspecific nature of TMS stimulation leads to specific neuronal reorganization, as well as a detailed picture of TMS-triggered reorganization of functional brain modules, is missing. Here we used real-time optical imaging in an animal experimental setting to track, at submillimeter range, TMS-induced functional changes in visual feature maps over several square millimeters of the brain's surface. We show that high-frequency TMS creates a transient cortical state with increased excitability and increased response variability, which opens a time window for enhanced plasticity. Visual stimulation (i.e., 30 min of passive exposure) with a single orientation applied during this TMS-induced permissive period led to enlarged imprinting of the chosen orientation on the visual map across visual cortex. This reorganization was stable for hours and was characterized by a systematic shift in orientation preference toward the trained orientation. Thus, TMS can noninvasively trigger a targeted large-scale remodeling of fundamentally mature functional architecture in early sensory cortex., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Induction of a central retinal lesion in both eyes of adult mammals is a model for macular degeneration and leads to retinotopic map reorganization in the primary visual cortex (V1). Here we characterized the spatiotemporal dynamics of molecular activity levels in the central and peripheral representation of five higher-order visual areas, V2/18, V3/19, V4/21a,V5/PMLS, area 7, and V1/17, in adult cats with central 10° retinal lesions (both sexes), by means of real-time PCR for the neuronal activity reporter gene zif268. The lesions elicited a similar, permanent reduction in activity in the center of the lesion projection zone of area V1/17, V2/18, V3/19, and V4/21a, but not in the motion-driven V5/PMLS, which instead displayed an increase in molecular activity at 3 months postlesion, independent of visual field coordinates. Also area 7 only displayed decreased activity in its LPZ in the first weeks postlesion and increased activities in its periphery from 1 month onward. Therefore we examined the impact of central vision loss on motion perception using random dot kinematograms to test the capacity for form from motion detection based on direction and velocity cues. We revealed that the central retinal lesions either do not impair motion detection or even result in better performance, specifically when motion discrimination was based on velocity discrimination. In conclusion, we propose that central retinal damage leads to enhanced peripheral vision by sensitizing the visual system for motion processing relying on feedback from V5/PMLS and area 7. SIGNIFICANCE STATEMENT Central retinal lesions, a model for macular degeneration, result in functional reorganization of the primary visual cortex. Examining the level of cortical reactivation with the molecular activity marker zif268 revealed reorganization in visual areas outside V1. Retinotopic lesion projection zones typically display an initial depression in zif268 expression, followed by partial recovery with postlesion time. Only the motion-sensitive area V5/PMLS shows no decrease, and even a significant activity increase at 3 months post-retinal lesion. Behavioral tests of motion perception found no impairment and even better sensitivity to higher random dot stimulus velocities. We demonstrate that the loss of central vision induces functional mobilization of motion-sensitive visual cortex, resulting in enhanced perception of moving stimuli., (Copyright © 2017 the authors 0270-6474/17/378989-11$15.00/0.)

In Germany, about 30,000 to 40,000 people suffer from retinitis pigmentosa (RP), which ultimately results in blindness. The only aid to blind RP patients are retinal implants: These have been under development for several years and have now been approved as a medical product. Retinal implants produce visual perceptions in response to electrical stimulation of the degenerated retina and are useful in the everyday life of blind people. However, the currently achievable quality of vision is such that people with a retinal implant are still legally blind. The visual quality that can be achieved with epi- and subretinal implants depends not only on patient-specific factors such as individual history and status of retinal degeneration, but especially on the interface between implant and retina and the quality of the achievable neuronal activation. Biophysical approaches to functional improvements of the implants are founded on the physiology of the retina (cell density, intraretinal interconnections), are based on technical optimisation of the interface (electrode materials, size and density), and exploit the stimulation protocols with which visual information is fed into the degenerated retina (time courses of electrical stimuli, spatiotemporal stimulation pattern). Optimisation of stimulation parameters can be supported by a detailed analysis of cortical responses, with appropriate electrophysiological and optical methods. This article looks at both the physiological and biophysical fundamentals of electrical retinal stimulation, as well as the resulting retinal and cortical activation., (Georg Thieme Verlag KG Stuttgart · New York.)

Mitochondria buffer intracellular Ca 2+ and provide energy [1]. Because synaptic structures with high Ca 2+ buffering [2-4] or energy demand [5] are often localized far away from the soma, mitochondria are actively transported to these sites [6-11]. Also, the removal and degradation of mitochondria are tightly regulated [9, 12, 13], because dysfunctional mitochondria are a source of reactive oxygen species, which can damage the cell [14]. Deficits in mitochondrial trafficking have been proposed to contribute to the pathogenesis of Parkinson's disease, schizophrenia, amyotrophic lateral sclerosis, optic atrophy, and Alzheimer's disease [13, 15-19]. In neuronal cultures, about a third of mitochondria are motile, whereas the majority remains stationary for several days [8, 20]. Activity-dependent mechanisms cause mitochondria to stop at synaptic sites [7, 8, 20, 21], which affects synapse function and maintenance. Reducing mitochondrial content in dendrites decreases spine density [22, 23], whereas increasing mitochondrial content or activity increases it [7]. These bidirectional interactions between synaptic activity and mitochondrial trafficking suggest that mitochondria may regulate synaptic plasticity. Here we investigated the dynamics of mitochondria in relation to axonal boutons of neocortical pyramidal neurons for the first time in vivo. We find that under these circumstances practically all mitochondria are stationary, both during development and in adulthood. In adult visual cortex, mitochondria are preferentially localized at putative boutons, where they remain for several days. Retinal-lesion-induced cortical plasticity increases turnover of putative boutons but leaves mitochondrial turnover unaffected. We conclude that in visual cortex in vivo, mitochondria are less dynamic than in vitro, and that structural plasticity does not affect mitochondrial dynamics., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Neuronal activity plays an important role in the development and structural-functional maintenance of the brain as well as in its life-long plastic response to changes in sensory stimulation. We characterized the impact of unilateral 15° laser lesions in the temporal lower visual field of the retina, on visually driven neuronal activity in the afferent visual pathway of adult mice using in situ hybridization for the activity reporter gene zif268. In the first days post-lesion, we detected a discrete zone of reduced zif268 expression in the contralateral hemisphere, spanning the border between the monocular segment of the primary visual cortex (V1) with extrastriate visual area V2M. We could not detect a clear lesion projection zone (LPZ) in areas lateral to V1 whereas medial to V2M, agranular and granular retrosplenial cortex showed decreased zif268 levels over their full extent. All affected areas displayed a return to normal zif268 levels, and this was faster in higher order visual areas than in V1. The lesion did, however, induce a permanent LPZ in the retinorecipient layers of the superior colliculus. We identified a retinotopy-based intrinsic capacity of adult mouse visual cortex to recover from restricted vision loss, with recovery speed reflecting the areal cortical magnification factor. Our observations predict incomplete visual field representations for areas lateral to V1 vs. lack of retinotopic organization for areas medial to V2M. The validation of this mouse model paves the way for future interrogations of cortical region- and cell-type-specific contributions to functional recovery, up to microcircuit level., (© 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Optical illusions have broadened our understanding of the brain's role in visual perception. A modern day optical illusion emerged from a posted photo of a striped dress, which some perceived as white and gold and others as blue and black. Here we show, using functional magnetic resonance imaging (fMRI), that those who perceive The Dress as white/gold have higher activation in response to the image of The Dress in brain regions critically involved in higher cognition (frontal and parietal brain areas). These results are consistent with theories of top-down modulation and present a neural signature associated with the differences in perceiving The Dress as white/gold or blue/black. Furthermore the results support recent psychophysiological data on this phenomenon and provide a fundamental building block to study interindividual differences in visual processing., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A common feature of the mammalian striate cortex is the arrangement of 'orientation domains' containing neurons preferring similar stimulus orientations. They are arranged as spokes of a pinwheel that converge at singularities known as 'pinwheel centers'. We propose that a cortical network of feedforward and intracortical lateral connections elaborates a full set of optimum orientations from geniculate inputs that show a bias to stimulus orientation and form a set of two or a small number of 'Cartesian' coordinates. Because each geniculate afferent carries signals only from one eye and its receptive field (RF) is either ON or OFF center, the network constructs also ocular dominance columns and a quasi-segregation of ON and OFF responses across the horizontal extent of the striate cortex., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Transcranial magnetic stimulation (TMS) is widely used in clinical interventions and basic neuroscience. Additionally, it has become a powerful tool to drive plastic changes in neuronal networks. However, highly resolved recordings of the immediate TMS effects have remained scarce, because existing recording techniques are limited in spatial or temporal resolution or are interfered with by the strong TMS-induced electric field. To circumvent these constraints, we performed optical imaging with voltage-sensitive dye (VSD) in an animal experimental setting using anaesthetized cats. The dye signals reflect gradual changes in the cells' membrane potential across several square millimeters of cortical tissue, thus enabling direct visualization of TMS-induced neuronal population dynamics. After application of a single TMS pulse across visual cortex, brief focal activation was immediately followed by synchronous suppression of a large pool of neurons. With consecutive magnetic pulses (10 Hz), widespread activity within this "basin of suppression" increased stepwise to suprathreshold levels and spontaneous activity was enhanced. Visual stimulation after repetitive TMS revealed long-term potentiation of evoked activity. Furthermore, loss of the "deceleration-acceleration" notch during the rising phase of the response, as a signature of fast intracortical inhibition detectable with VSD imaging, indicated weakened inhibition as an important driving force of increasing cortical excitability. In summary, our data show that high-frequency TMS changes the balance between excitation and inhibition in favor of an excitatory cortical state. VSD imaging may thus be a promising technique to trace TMS-induced changes in excitability and resulting plastic processes across cortical maps with high spatial and temporal resolutions.

The nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling cascade participates in the modulation of synaptic transmission. The effects of NO are mediated by the NO-sensitive cGMP-forming guanylyl cyclases (NO-GCs), which exist in 2 isoforms with indistinguishable regulatory properties. The lack of long-term potentiation (LTP) in knock-out (KO) mice deficient in either one of the NO-GC isoforms indicates the contribution of both NO-GCs to LTP. Recently, we showed that the NO-GC1 isoform is located presynaptically in glutamatergic neurons and increases the glutamate release via hyperpolarization-activated cyclic nucleotide (HCN)-gated channels in the hippocampus. Electrophysiological analysis of hippocampal CA1 neurons in whole-cell recordings revealed a reduction of HCN currents and a hyperpolarizing shift of the activation curve in the NO-GC2 KOs associated with reduced resting membrane potentials. These features were mimicked in wild-type (WT) neurons with an NO-GC inhibitor. Analysis of glutamate receptors revealed a cGMP-dependent reduction of NMDA receptor currents in the NO-GC2 KO mice, which was mimicked in WT by HCN channel inhibition. Lowering extracellular Mg(2+) increased NMDA receptor currents in the NO-GC2 KO and allowed the induction of LTP that was absent at physiological Mg(2+). In sum, our data indicate that postsynaptic cGMP increases the N-methyl-D-aspartate (NMDA) receptor current by gating HCN channels and thereby is required for LTP., (© The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Homeostatic plasticity is important to maintain a set level of activity in neuronal circuits and has been most extensively studied in cell cultures following activity blockade. It is still unclear, however, whether activity changes associated with mechanisms of homeostatic plasticity occur in vivo, for example after changes in sensory input. Here, we show that activity levels in the visual cortex are significantly decreased after sensory deprivation by retinal lesions, followed by a gradual increase in activity levels in the 48 hr after deprivation. These activity changes are associated with synaptic scaling, manifested in vitro by an increase in mEPSC amplitude and in vivo by an increase in spine size. Together, these data show that homeostatic activity changes occur in vivo in parallel with synaptic scaling., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Reduction in the strength of GABAergic neurotransmission has often been reported following brain lesions. This weakened inhibition is believed to influence neurological deficits, neuronal hyperexcitability and functional recovery after brain injuries. Uncovering the mechanisms underlying the altered inhibition is therefore crucial. In the present study we used an ex vivo-in vitro model of laser lesions in the rat visual cortex to characterize the cellular correlates of changes in GABAergic transmission in the tissue adjacent to the injury. In the first week post-injury the number of VGAT positive GABAergic terminals as well as the expression level of the GABA synthesizing enzymes GAD67 and GAD65 remained unaltered. However, a reduced frequency of miniature inhibitory postsynaptic currents (mIPSCs) together with an increased paired-pulse ratio (PPR) of evoked IPSCs suggested a functional reduction of phasic GABA release. In parallel, we found an enhancement in the GABAA receptor-mediated tonic inhibition. On the basis of these findings, we propose that cortical lesions provoke a shift in GABAergic transmission, decreasing the phasic and reinforcing the tonic component. We therefore suggest that it is not, as traditionally assumed, the overall inhibitory strength to be primarily compromised by a cortical lesion but rather the temporal accuracy of the GABAergic synaptic signaling.

Focal brain injuries are accompanied by processes of functional reorganization that partially compensate the functional loss. In a previous study, extracellular recordings at the border of a laser-induced lesion in the visual cortex of rats showed an enhanced synaptic plasticity, which was mediated by the activity of NR2B-contaning NMDA-receptors (NMDARs) shedding light on the potential cellular mechanisms underlying this reorganization. Given the potentially important contribution of NMDARs in processes of functional reorganization, in the present study, we used the same lesion model to further investigate lesion-induced changes in function and localization of NMDARs in the vicinity of the lesion. The most important finding was a lesion-mediated functional reexpression of nonpostsynaptic, but according to our data, presynaptic or peri-/extrasynaptic NMDARs (preNMDARs), which were undetectable in age-matched (>P21) sham-operated controls. Notably, preNMDARs were able to boost both spontaneous and evoked synaptic glutamatergic transmission. At the postsynaptic site, we also disclosed an increase in the decay time constant of NMDARs mediated currents, which was accompanied by a decreased NR2A/NR2B ratio, as revealed by Western blot analysis. All together these findings provide new insights into the role of NMDARs activity during processes of functional reorganization following a focal lesion in the cerebral cortex.

CNS lesions generally result in impaired function because regeneration of the adult CNS of mammals is poor. A variety of lesion models has been described that serve to further the understanding of the pathophysiology of the damaged tissue. A central cause of aborted regeneration is the glial scar that expresses a plethora of extracellular matrix molecules. Some of these are considered inhibitors of axon growth and regeneration. The laser lesion of the cortex offers the advantage that a circumscribed lesion of defined energy can be delivered to the cortex non-invasively through the intact dura mater and a thinly drilled wet translucent remnant of the skull. Previously, we have shown that distinct ECM is up-regulated in the penumbra of laser lesions in the rat visual cortex. We propose to transfer this model to the mouse, in view of the availability of a large number of genetical models in this small rodent. Here, we discuss this model and the lesion-related ECM that forms the focus of our analysis.

In cats with central retinal lesions, deprivation of the lesion projection zone (LPZ) in primary visual cortex (area 17) induces remapping of the cortical topography. Recovery of visually driven cortical activity in the LPZ involves distinct changes in protein expression. Recent observations, about molecular activity changes throughout area 17, challenge the view that its remote nondeprived parts would not be involved in this recovery process. We here investigated the dynamics of the protein expression pattern of remote nondeprived area 17 triggered by central retinal lesions to explore to what extent far peripheral area 17 would contribute to the topographic map reorganization inside the visual cortex. Using functional proteomics, we identified 40 proteins specifically differentially expressed between far peripheral area 17 of control and experimental animals 14 days to 8 months postlesion. Our results demonstrate that far peripheral area 17 is implicated in the functional adaptation to the visual deprivation, involving a meshwork of interacting proteins, operating in diverse pathways. In particular, endocytosis/exocytosis processes appeared to be essential via their intimate correlation with long-term potentiation and neurite outgrowth mechanisms.

A fundamental property of neuronal circuits is the ability to adapt to altered sensory inputs. It is well established that the functional synaptic changes underlying this adaptation are reflected by structural modifications in excitatory neurons. In contrast, the degree to which structural plasticity in inhibitory neurons accompanies functional changes is less clear. Here, we use two-photon imaging to monitor the fine structure of inhibitory neurons in mouse visual cortex after deprivation induced by retinal lesions. We find that a subset of inhibitory neurons carry dendritic spines, which form glutamatergic synapses. Removal of visual input correlates with a rapid and lasting reduction in the number of inhibitory cell spines. Similar to the effects seen for dendritic spines, the number of inhibitory neuron boutons dropped sharply after retinal lesions. Together, these data suggest that structural changes in inhibitory neurons may precede structural changes in excitatory circuitry, which ultimately result in functional adaptation following sensory deprivation., (Copyright © 2011 Elsevier Inc. All rights reserved.)

In hippocampal neurons, synaptic transmission is affected by a variety of modulators, including nitric oxide (NO), which was proposed as a retrograde messenger as long as two decades ago. NO signals via two NO-sensitive guanylyl cyclases (NO-GCs) (NO-GC1 and NO-GC2) and the subsequent increase in cGMP. Lack of long-term potentiation in mice deficient in either one of the two NO-GCs demonstrates the involvement of both NO-GCs in synaptic transmission. However, the physiological consequences of NO/cGMP and the cellular mechanisms involved are unknown. Here, we analyzed glutamatergic synaptic transmission, most likely reflecting glutamate release, in the hippocampal CA1 region of NO-GC knockout mice by single-cell recording, and found glutamate release to be reduced under basal and stimulated conditions in the NO-GC1 knockout mice, but restorable to wild-type-like levels with a cGMP analog. Conversely, an inhibitor of NO/cGMP signaling, ODQ, reduced glutamate release in wild-type mice to knockout-like levels; thus, we conclude that presynaptic cGMP formed by NO-GC1 facilitates glutamate release. In this pathway, NO is supplied by endothelial NO synthase. In search of a cGMP target, we found that two mechanistically distinct blockers of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels (ZD7288 and DK-AH269) abolished the cGMP-induced increase in glutamate release, suggesting that cGMP either directly or indirectly signals via HCN channels. In summary, we unravel a presynaptic role of NO/cGMP most likely in glutamate release and propose that HCN channels act as effectors for cGMP., (© 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.)

Human cortical excitability can be modified by repetitive transcranial magnetic stimulation (rTMS), but the cellular mechanisms are largely unknown. Here, we show that the pattern of delivery of theta-burst stimulation (TBS) (continuous versus intermittent) differently modifies electric activity and protein expression in the rat neocortex. Intermittent TBS (iTBS), but not continuous TBS (cTBS), enhanced spontaneous neuronal firing and EEG gamma band power. Sensory evoked cortical inhibition increased only after iTBS, although both TBS protocols increased the first sensory response arising from the resting cortical state. Changes in the cortical expression of the calcium-binding proteins parvalbumin (PV) and calbindin D-28k (CB) indicate that changes in spontaneous and evoked cortical activity following rTMS are in part related to altered activity of inhibitory systems. By reducing PV expression in the fast-spiking interneurons, iTBS primarily affected the inhibitory control of pyramidal cell output activity, while cTBS, by reducing CB expression, more likely affected the dendritic integration of synaptic inputs controlled by other classes of inhibitory interneurons. Calretinin, the third major calcium-binding protein expressed by another class of interneurons was not affected at all. We conclude that different patterns of TBS modulate the activity of inhibitory cell classes differently, probably depending on the synaptic connectivity and the preferred discharge pattern of these inhibitory neurons.

Focal cortical injuries are accompanied by a reorganization of the adjacent neuronal networks. An increased synaptic plasticity has been suggested to mediate, at least in part, this functional reorganization. Previous studies showed an increased long-term potentiation (LTP) at synapses formed by ascending fibres projecting onto layers 2/3 pyramidal cells following lesions in rat visual cortex. This could be important to establish new functional connections within a vertical cortical column. Importantly, horizontal intracortical connections constitute an optimal substrate to mediate the functional reorganization across different cortical columns. However, so far little is known about their potential implication in the functional rewiring post-lesion. Here, we investigated possible alterations of synaptic plasticity of horizontal connections in layers 2/3 in an 'ex vivo-in vitro' model of focal laser lesion in rat visual cortex. LTP at these synapses was found to be enhanced post-lesion, whereas long-term depression (LTD) was impaired, revealing a metaplastic shift toward strengthening of these synapses. Furthermore, we disclosed a prolonged decay-time constant of NMDAR-dependent currents, which can contribute to the enhanced LTP. Taken together these data revealed that a laser lesion-induced focal damage of the visual cortex is accompanied by a facilitated potentiation of horizontal synaptic connections in the vicinity of the focal injury. This specific strengthening of synaptic plasticity at horizontal connections in layers 2/3 might be one important cellular mechanism to compensate focal injury-mediated dysfunction in the cerebral cortex.

Repetitive transcranial magnetic stimulation (rTMS) can modulate cortical excitability in a stimulus-frequency-dependent manner. Two kinds of theta burst stimulation (TBS) [intermittent TBS (iTBS) and continuous TBS (cTBS)] modulate human cortical excitability differently, with iTBS increasing it and cTBS decreasing it. In rats, we recently showed that this is accompanied by changes in the cortical expression of proteins related to the activity of inhibitory neurons. Expression levels of the calcium-binding protein parvalbumin (PV) and of the 67-kDa isoform of glutamic acid decarboxylase (GAD67) were strongly reduced following iTBS, but not cTBS, whereas both increased expression of the 65-kDa isoform of glutamic acid decarboxylase. In the present study, to investigate possible functional consequences, we applied iTBS and cTBS to rats learning a tactile discrimination task. Conscious rats received either verum or sham rTMS prior to the task. Finally, to investigate how rTMS and learning effects interact, protein expression was determined for cortical areas directly involved in the task and for those either not, or indirectly, involved. We found that iTBS, but not cTBS, improved learning and strongly reduced cortical PV and GAD67 expression. However, the combination of learning and iTBS prevented this effect in those cortical areas involved in the task, but not in unrelated areas. We conclude that the improved learning found following iTBS is a result of the interaction of two effects, possibly in a homeostatic manner: a general weakening of inhibition mediated by the fast-spiking interneurons, and re-established activity in those neurons specifically involved in the learning task, leading to enhanced contrast between learning-induced and background activity., (© 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.)

Quantitative analysis of the neuronal activity marker Fos revealed activity-dependent and lamina-specific changes in adult cat area 17, 14 days to 1 month after the induction of central retinal lesions. The supra- and infragranular layers were clearly differently engaged in the response to the visual deprivation, both inside and outside the lesion projection zone. The center of the LPZ exhibited an activity decrease in the extragranular layers, which was mainly reflected by an intracellular down-regulation of Fos rather than a decline in the number of Fos-immunoreactive nuclei. Interestingly, the infragranular layers displayed more Fos-immunoreactive neurons in experimental animals. This recruitment of an additional population of Fos expressing neurons in the subcortically projecting infragranular layers might have a protective function against neurodegeneration in the direct retinal target structures.

The brain contains a complex network of axons rapidly communicating information between billions of synaptically connected neurons. The morphology of individual axons, therefore, defines the course of information flow within the brain. More than a century ago, Ramón y Cajal proposed that conservation laws to save material (wire) length and limit conduction delay regulate the design of individual axon arbors in cerebral cortex. Yet the spatial and temporal communication costs of single neocortical axons remain undefined. Here, using reconstructions of in vivo labelled excitatory spiny cell and inhibitory basket cell intracortical axons combined with a variety of graph optimization algorithms, we empirically investigated Cajal's conservation laws in cerebral cortex for whole three-dimensional (3D) axon arbors, to our knowledge the first study of its kind. We found intracortical axons were significantly longer than optimal. The temporal cost of cortical axons was also suboptimal though far superior to wire-minimized arbors. We discovered that cortical axon branching appears to promote a low temporal dispersion of axonal latencies and a tight relationship between cortical distance and axonal latency. In addition, inhibitory basket cell axonal latencies may occur within a much narrower temporal window than excitatory spiny cell axons, which may help boost signal detection. Thus, to optimize neuronal network communication we find that a modest excess of axonal wire is traded-off to enhance arbor temporal economy and precision. Our results offer insight into the principles of brain organization and communication in and development of grey matter, where temporal precision is a crucial prerequisite for coincidence detection, synchronization and rapid network oscillations.

Focal visual cortex lesions lead to functional changes in the surrounding cortical network, possibly mediated through synaptic long-term potentiation (LTP). Although a post-lesional facilitation of LTP has been observed, nothing is known about the spatial profile of LTP in the normal and focally lesioned visual cortex of rats. We used a 64-multielectrode array to characterise the spread of LTP induced by theta-burst stimulation in layer IV. Measurements were made at comparable distances from the midline in the visual cortex of controls, sham-operated and lesioned animals. In control rats, LTP was elicited in projections to all visual cortex layers. However, we completely failed to observe LTP in sham-operated animals 1-4 days after surgery. At comparable survival times, no LTP could be elicited in the lesion-treated rats in direct vicinity of the border of the injury, while LTP was successfully induced at larger distances from the lesion. The maximal reach of this restored post-lesion LTP was spatially more limited than in controls and equal in all directions, accordingly absolute distance and not maximal length or density of connections seems to rule local lesion-induced functional remodelling., (© Springer-Verlag 2009)

Background: Optic nerve sheath fenestration (ONSF) is a surgical procedure that is sometimes performed in patients with optic disc edema from increased intracranial pressure. The objective of this study was to assess the consequence of ONSF on optic nerve axons, retinal ganglion cells (RGCs), and retinal amacrine cells., Methods: The optic nerves of 22 male Wistar rats were assigned to one of three groups. In Group 1 (n = 12), the rats underwent unilateral ONSF. In Group 2 (n = 10), the rat optic nerves were unilaterally exposed but were not operated on. Group 3 (n = 22) consisted of the optic nerves of Group 1 and Group 2 rats that were neither operated on nor exposed. Thirty days later, a cresyl violet staining method was used to assess the number and sizes of RGCs and amacrine cells. Optic nerve axons were assessed by means of glial fibrillary acidic protein (GFAP) immunoreactivity., Results: ONSF was associated with a significant reduction (P < 0.05) in the number and size of RGCs and amacrine cells. Optic nerve axons were undisturbed., Conclusions: Although ONSF does not apparently injure the optic nerve axons, loss and shrinkage of RGCs is a caution when considering ONSF as a treatment.

Retinal lesions induce a topographic reorganization in the corresponding lesion projection zone (LPZ) in the visual cortex of adult cats. To gain a better insight into the reactivation dynamics, we investigated the alterations in cortical activity throughout area 17. We implemented in situ hybridization and real-time polymerase chain reaction to analyze the spatiotemporal expression patterns of the activity marker genes zif268 and c-fos. The immediate early gene (IEG) data confirmed a strong and permanent activity decrease in the center of the LPZ as previously described by electrophysiology. A recovery of IEG expression was clearly measured in the border of the LPZ. We were able to register reorganization over 2.5-6 mm. We also present evidence that the central retinal lesions concomitantly influence the activity in far peripheral parts of area 17. Its IEG expression levels appeared dependent of time and distance from the LPZ. We therefore propose that coupled changes in activity occur inside and outside the LPZ. In conclusion, alterations in activity reporter gene expression throughout area 17 contribute to the lesion-induced functional reorganization.

The functional specificity of callosal connections was investigated in visual areas 17 and 18 of adult cats, by combining in vivo optical imaging of intrinsic signals with labeling of callosal axons. Local injections of neuronal tracers were performed in one hemisphere and eight single callosal axons were reconstructed in the opposite hemisphere. The distributions of injection sites and callosal axon terminals were analyzed with respect to functional maps in both hemispheres. Typically, each callosal axon displayed 2 or 3 clusters of synaptic boutons in layer II/III and the upper part of layer IV. These clusters were preferentially distributed in regions representing the same orientation and the same visuotopic location as that at the corresponding injection sites in the opposite hemisphere. The spatial distribution of these clusters was elongated and its main axis correlated well with the preferred orientation at the injection site. These results demonstrate a specific organization of interhemispheric axons that link cortical regions representing the same orientation and the same location of visual stimuli. Visual callosal connections are thus likely involved in the processing of coherent information in terms of shape and position along the midline of the visual field, which may facilitate the fusion of both hemifields into the percept of a single visual scene.

The regulation of protein phosphorylation plays an essential role in virtually all aspects of eukaryotic development. Beginning with the regulation of the cell cycle to cellular proliferation and differentiation, the delicate balance between the phosphorylating activity of kinases and the dephosphorylation by phosphatases controls the outcome of many signal transduction cascades. The generation of cellular diversity occurs in an environment that is structured by the extracellular matrix (ECM) which forms a surrounding niche for stem and progenitor cells. Cell-cell and cell-matrix interactions elicit specific signaling pathways that control cellular behavior. In pathological situations such as neural degenerating diseases, gene expression patterns and finally the composition of the ECM change dramatically. This leads to changes of cell behavior and finally results in the failure of regeneration and functional restoration in the adult central nervous system. In order to study the roles of tyrosine phosphatases and ECM in this context, we analyzed the effects of laser-induced retinal injury on the regulation of the receptor protein tyrosine phosphatases (RPTP) RPTPBr7, Phogrin and RPTPbeta/zeta. The latter occurs in several isoforms, including the soluble released chondroitin sulfate proteoglycan phosphacan that is expressed in the developing retina. The receptor variants RPTPbeta/zeta(long) and RPTPbeta/zeta(short) may serve as receptors of tenascin-proteins and serve as modulators of cell intrinsic signaling in response to the ECM. Using quantitative real-time RT-PCR analysis, we show here a time-dependent pattern of gene expression of these molecules following laser lesions of the retina.

CNS lesions stimulate adult neurogenic niches. Endogenous neural stem/progenitor cells represent a potential resource for CNS regeneration. Here, we investigate the response to unilateral focal laser-lesions applied to the visual cortex of juvenile rats. Within 3 days post-lesion, an ipsilateral increase of actively cycling cells was observed in cortical layer one and in the callosal white matter within the lesion penumbra. The cells expressed the neural stem/progenitor cell marker Nestin and the 473HD-epitope. Tissue prepared from the lesion area by micro-dissection generated self-renewing, multipotent neurospheres, while cells from the contralateral visual cortex did not. The newly formed neural stem/progenitor cells in the lesion zone might support neurogenesis, as suggested by the expression of Pax6 and Doublecortin, a marker of newborn neurons. We propose that focal laser-lesions may induce the emergence of stem/progenitor cells with neurogenic potential. This could underlie the beneficial effects of laser application in neurosurgery.

Although nitric oxide (NO) has been implicated as a messenger molecule in hippocampal long-term potentiation (LTP) for almost 20 years, its precise function has not been elucidated because presynaptic and/or postsynaptic actions of NO have been reported. Most of the effects of NO as a signaling molecule are mediated by the NO receptor guanylyl cyclases (NO-GCs), two heme-containing enzymes with pronounced homology in which cGMP-forming activity is stimulated on NO binding. Here we report on knock-out (KO) mice in which either one of the NO-GC receptors has been genetically deleted. By measuring NO-induced cGMP levels, similar quantities of both NO-GC receptors were determined in the hippocampus. Surprisingly, hippocampal LTP was abolished in either one of the KO strains, demonstrating that both NO-GC receptors are required in the course of LTP. Expression of LTP was restored with a cGMP analog in one of the KO strains but did not recover in the other one. Moreover, single-cell recordings of paired pulse facilitation revealed a presynaptic role of one of the NO-GC isoforms in neurotransmitter release, confirming different roles of the NO-GC receptors in LTP. Because neither one of the NO/cGMP-induced responses by itself is sufficient for LTP, two divergent, possibly presynaptically and postsynaptically localized NO-stimulated cGMP pathways are apparently required for the expression of LTP. The unexpected role of cGMP at two sites of the synaptic cleft explains many of the controversial results in former NO research in LTP and demonstrates the necessity of presynaptic and postsynaptic changes for LTP expression.

Sensory deprivation caused by peripheral injury can trigger functional cortical reorganization across the initially silenced cortical area. It is proposed that intracortical connectivity enables recovery of function within such a lesion projection zone (LPZ), thus substituting lost subcortical input. Here, we investigated retinal lesion-induced changes in the function of lateral connections in the primary visual cortex of the adult rat. Using voltage-sensitive dye recordings, we visualized in millisecond-time resolution spreading synaptic activity across the LPZ. Shortly after lesion, the majority of neurons within the LPZ were subthresholdly activated by delayed propagation of activity that originated from unaffected cortical regions. With longer recovery time, latencies within the LPZ gradually decreased, and activation reached suprathreshold levels. Targeted electrode recordings confirmed that receptive fields of intra-LPZ neurons were displaced to the retinal lesion border while displaying normal orientation and direction selectivity. These results corroborate the view that cortical horizontal connections have a central role in functional reorganization, as revealed here by progressive facilitation of synaptic activity and the traveling wave of excitation that propagates horizontally into the deprived cortical region.

The role of GABAergic inhibition in orientation and direction selectivity has been investigated with the GABA(A)-Blocker bicuculline in the cat visual cortex, and results indicated a region specific difference of functional contributions of GABAergic inhibition in areas 17 and 18. In area 17 inhibition appeared mainly involved in sculpturing orientation and direction tuning, while in area 18 inhibition seemed more closely associated with temporal receptive field properties. However, different types of stimuli were used to test areas 17 and 18 and further studies performed in area 17 suggested an important influence of the stimulus type (single light bars vs. moving gratings) on the evoked responses (transient vs. sustained) and inhibitory mechanisms (GABA(A) vs. GABA(B)) which in turn might be more decisive for the specific results than the cortical region. To insert the missing link in this chain of arguments it was necessary to study GABAergic inhibition in area 18 with moving light bars, which has not been done so far. Therefore, in the present study we investigated area 18 cells responding to oriented moving light bars with extracellular recordings and reversible microiontophoretic blockade of GABAergig inhibition with bicuculline methiodide. The majority of neurons was characterized by a pronounced orientation specificity and variable degrees of direction selectivity. GABA(A)ergic inhibition significantly influenced preferred orientation and preferred direction in area 18. During the action of bicuculline orientation tuning width increased and orientation and direction selectivity indices decreased. Our results obtained in area 18 with moving bar stimuli, although in the proportion of affected cells similar to those described in area 17, quantitatively matched the findings for direction and orientation specificity obtained with moving gratings in area 18. Accordingly, stimulus type is not decisive in area 18 and the GABA(A) dependent, inhibitory intracortical computations involved in orientation specificity are indeed region-specific and in comparison to area 17 less effective in area 18.

The primary somatosensory cortex (SI) retains its capability for cortical reorganization after injury or differential use into adulthood. The plastic response of SI cells to peripheral stimulation is characterized by extension of cortical representations accompanied by changes of the receptive field size of neurons. We used intracortical microstimulation that is known to enforce local, intracortical synchronous activity, to induce cortical reorganization and applied immunohistochemical methods in the same individual animals to investigate how plasticity in the cortical topographic maps is linked to changes in the spatial layout of the inhibitory and excitatory neurotransmitter systems. The results reveal a differential spatiotemporal pattern of upregulation and downregulation of specific factors for an excitatory (glutamatergic) and an inhibitory (GABAergic) system, associated with changes of receptive field size and reorganization of the somatotopic map in the rat SI. Predominantly local mechanisms are the specific reduction of the calcium-binding protein parvalbumin in inhibitory neurons and the low expression of the activity marker c-Fos. Reorganization in the hindpaw representation and in the adjacent SI cortical areas (motor cortex and parietal cortex) is accompanied by a major increase of the excitatory transmitter glutamate and c-Fos. The spatial extent of the reorganization appears to be limited by an increase of glutamic acid decarboxylase and the inhibitory transmitter GABA. The local and medium-range net effects are excitatory and can facilitate receptive field enlargements and cortical map expansion. The longer-range increase of inhibition appears suited to limit these effects and to prevent neurons from pathological hyperexcitability.

The cerebral cortex has the ability to adapt to altered sensory inputs. In the visual cortex, a small lesion to the retina causes the deprived cortical region to become responsive to adjacent parts of the visual field. This extensive topographic remapping is assumed to be mediated by the rewiring of intracortical connections, but the dynamics of this reorganization process remain unknown. We used repeated intrinsic signal and two-photon imaging to monitor functional and structural alterations in adult mouse visual cortex over a period of months following a retinal lesion. The rate at which dendritic spines were lost and gained increased threefold after a small retinal lesion, leading to an almost complete replacement of spines in the deafferented cortex within 2 months. Because this massive remodeling of synaptic structures did not occur when all visual input was removed, it likely reflects the activity-dependent establishment of new cortical circuits that serve the recovery of visual responses.

Repetitive transcranial magnetic stimulation (rTMS) has been shown to alter cortical excitability depending on the stimulus-frequency used, with high frequency (5 Hz and higher) increasing it but low frequency (usually 1 Hz or lower) reducing it. To determine the efficiency of different rTMS protocols in inducing cortical network activity, we tested the acute effect of one low-frequency rTMS protocol (1 Hz) and two different high-frequency protocols (10 Hz and intermittent theta-burst stimulation, iTBS) on the expression of the two immediate early gene (IEG) proteins c-Fos and zif268 in the rat brain. The cortical expression of both IEGs was specifically changed in an rTMS-dependent manner. One and 10 Hz rTMS enhanced c-Fos protein expression in all cortical areas tested, while iTBS was effective only in limbic cortices. Zif268 expression was increased in almost all cortical areas after iTBS, while 10 Hz rTMS was effective only in the primary motor and sensory cortices. One Hertz rTMS had no effect on cortical zif268 expression. Furthermore, sham-rTMS had no effect on zif268 expression but increased c-Fos in limbic cortices. This is the first study demonstrating that cortical zif268 and c-Fos expression can be specifically modulated by acute rTMS depending on the pattern of stimulation applied.

Brain derived neurotrophic factor (BDNF) promotes the formation, maturation and stabilization of inhibitory synapses in the central nervous system. In addition, BDNF has been suggested to regulate the critical period for ocular dominance plasticity in the visual system. Here we further evaluated the role of BDNF in the visual cortex by studying the GABAergic synaptic transmission under conditions of chronically reduced levels of BDNF. Whole-cell patch-clamp recordings were performed from pyramidal neurons located in layers II/III of visual cortical slices in heterozygous BDNF knockout mice (BDNF (+/-)) and their wild-type littermates at the age of 21-25 days. The BDNF (+/-) mice showed a decreased frequency and amplitude of miniature inhibitory postsynaptic currents (mIPSCs) as well as a reduced amplitude and prolonged decay time constant of evoked IPSCs. Further analyses indicated an impaired presynaptic GABAergic function in BDNF (+/-) mice, as shown by the decreased release probability, steady-state release and synchronous release of GABA. However, the number of functional release sites remained unchanged. In line with these observations, an impaired glutamate-driven GABA release was observed in BDNF (+/-) mice. Furthermore, the overall balance in the strength of cortical excitation to inhibition shifted towards a decreased inhibition. Finally, the reversal potential for chloride-mediated evoked IPSCs was not affected. These findings suggested that chronically reduced levels of BDNF strongly impair the GABAergic inhibitory function in visual cortex by altering postsynaptic properties and by reducing presynaptic GABA release as well as the overall strength of inhibition onto pyramidal neurons within the cortical network. These impairments of inhibitory function are compatible with a rather immature status of the GABAergic system in BDNF (+/-) mice, which supports the hypothesis that the level of expression for BDNF critically affects maturation and function of the GABAergic inhibition.

A unique and unresolved property of the central nervous system is that its extracellular matrix lacks fibrillar elements. In the present report, we show that astrocytes secrete triple helices of fibrillar collagens type I, III and V in culture, while no astroglial collagen expression could be detected in vivo. We discovered two inhibitory mechanisms that could underlie this apparent discrepancy. Thus, we uncover a strong inhibitory effect of meningeal cells on astrocytic collagen expression in coculture assays. Furthermore, we present evidence that EGF-receptor activation downregulates collagen expression in astrocytes via an autocrine loop. These investigations provide a rational framework to explain why the brain is devoid of collagen fibers, which is a unique feature that characterizes the structure of the neural extracellular matrix. Moreover, fibrillar collagens were found transiently upregulated in a laser-induced cortical lesion, suggesting that these could contribute to the glial scar that inhibits axonal regeneration.

The contribution of interhemispheric connections to functional maps in cat visual cortex was investigated by using optical imaging of intrinsic signals. In order to isolate the functional inputs arriving via the corpus callosum (CC) from other inputs, we used the split-chiasm preparation. The regions activated through the CC in visual areas 17 (A17) and 18 (A18) were localized and characterized by stimulating monocularly split-chiasm cats with moving, high contrast oriented gratings. We found that the CC mediates the activation of orientation selective domains in the transition zone (TZ) between A17 and A18 and occasionally within portions of both of these areas. We observed transcallosally activated orientation domains all along the TZ without any obvious interruption, and these domains were arranged around "pinwheel" centers. Interestingly, the TZ was divided in two parallel regions, which resemble A17 and A18 in their preferred temporal and spatial frequencies. Finally, we demonstrated that orientation maps evoked through the transcallosal and geniculo-cortical pathways were similar within the TZ, indicating a convergence of inputs of matching orientations in this region. These results contribute to a better understanding of the role of the CC in visual perception of orientations and shapes, at the level of the visual cortex.