Visual Cortex Of Adult Cats Research Articles

Relation between gamma oscillations and neuronal plasticity in the visual cortex

Use-dependent long-term changes of neuronal response properties must be gated to prevent irrelevant activity from inducing inappropriate modifications. Here we test the hypothesis that local network dynamics contribute to such gating. As synaptic modifications depend on temporal contiguity between presynaptic and postsynaptic activity, we examined the effect of synchronized gamma (ɣ) oscillations on stimulation-dependent modifications of orientation selectivity in adult cat visual cortex. Changes of orientation maps were induced by pairing visual stimulation with electrical activation of the mesencephalic reticular formation. Changes in orientation selectivity were assessed with optical recording of intrinsic signals and multiunit recordings. When conditioning stimuli were associated with strong ɣ-oscillations, orientation domains matching the orientation of the conditioning grating stimulus became more responsive and expanded, because neurons with preferences differing by less than 30° from the orientation of the conditioning grating shifted their orientation preference toward the conditioned orientation. When conditioning stimuli induced no or only weak ɣ-oscillations, responsiveness of neurons driven by the conditioning stimulus decreased. These differential effects depended on the power of oscillations in the low ɣ-band (20 Hz to 48 Hz) and not on differences in discharge rate of cortical neurons, because there was no correlation between the discharge rates during conditioning and the occurrence of changes in orientation preference. Thus, occurrence and polarity of use-dependent long-term changes of cortical response properties appear to depend on the occurrence of ɣ-oscillations during induction and hence on the degree of temporal coherence of the change-inducing network activity.

Fluoxetine and serotonin facilitate attractive-adaptation-induced orientation plasticity in adult cat visual cortex

Neurons in V1 display orientation selectivity by responding optimally to a preferred orientation edge when it is presented within their receptive fields. Orientation plasticity in striate cortex occurs either by ocular deprivation or by imposition of a non-preferred stimulus for several minutes. Adaptation of neurons to a non-optimal orientation induces shifts of tuning curves towards the adapting orientation (attractive shift) or away from it (repulsive shift). Here, we investigated the effects of the neurotransmitter serotonin and antidepressant fluoxetine (a selective serotonin reuptake inhibitor) on the modulation of adaptation-induced orientation plasticity. We show that serotonin and fluoxetine promote mostly attractive shifts. Attractive shifts augmented in magnitude towards adapter, whereas repulsive neurons reversed their behavior in the direction of the forced orientation. Furthermore, neurons which retained their original preferred orientation expressed plasticity by shifting their tuning curves after drug administration mostly towards adapter. Our data suggest a pre-eminent role of fluoxetine by inducing and facilitating short-term plasticity in V1.

Rapid Plasticity of Visual Responses in the Adult Lateral Geniculate Nucleus

Compared to the developing visual system, where neuronal plasticity has been well characterized at multiple levels, little is known about plasticity in the adult, particularly within subcortical structures. We made intraocular injections of 2-amino-4-phosphonobutyric acid (APB) in adult cats to block visual responses in On-center retinal ganglion cells and examined the consequences on visual responses in the lateral geniculate nucleus (LGN) of the thalamus. In contrast to current views of retinogeniculate organization, which hold that On-center LGN neurons should become silent with APB, we find that ∼50% of On-center neurons rapidly develop Off-center responses. The time course of these emergent responses and the actions of APB in the retina indicate the plasticity occurs within the LGN. These results suggest there is greater divergence of retinogeniculate connections than previously recognized and that functionally silent, nonspecific retinal inputs can serve as a substrate for rapid plasticity in the adult.

Wiring Economy of Neocortical Axon Arbors

Event Abstract Back to Event Wiring Economy of Neocortical Axon Arbors J. M. Budd1*, K. Kovács2, A. S. Ferecskó3, P. Buzás4, U. T. Eysel2 and Z. F. Kisvárday5 1 University of Sussex, School of Informatics, United Kingdom 2 Ruhr-Universität Bochum, Department of Neurophysiology, Germany 3 University of Birmingham, College of Medical & Dental Sciences, School of Clinical & Experimental Medicine, United Kingdom 4 University of Pécs, Institute of Physiology, Medical School, Hungary 5 University of Debrecen, Department of Anatomy, Histology & Embryology, Hungary Discovering the organizational principles of cerebral cortex represents a fundamental challenge in neuroscience. Rámon y Cajal proposed that general laws of conservation concerning cellular material (axon and dendritic ‘wire’) and conduction delay regulate neuronal morphology. Yet despite more than a century of research it is not known how well these laws apply to axon arbors in neocortex. Using a variety of graph optimization algorithms, we investigated Cajal’s proposed economy laws in relation to detailed 3D reconstructions of spiny and basket cell axon arbors obtained from in vivo labelling experiments in adult cat visual cortex. Our analysis of these data suggests that individual neocortical axon arbors are not minimized for axonal length (cellular material) but neither are they optimized for conduction delay. Instead neocortical axon arbors in contacting thousands of spatially distributed postsynaptic targets appear to trade-off saving axonal wire for more rapid communication. In particular, the branched structure of neocortical arbors seems to preserve the relationship between axonal propagation latency and cortical distance and ensures a low degree of temporal dispersion axonal latencies, which may be tighter for inhibitory basket cell than excitatory spiny cell axons. This work has implications for our understanding of neocortical organizing principles, coding, and communication. Acknowledgements Research funded by MTA-TKI (242), DFG (SFB509), and the FACETS (FP6-IST-FETPI) project. Keywords: Molecular and cellular neurobiology, Neuroscience Conference: 13th Conference of the Hungarian Neuroscience Society (MITT), Budapest, Hungary, 20 Jan - 22 Jan, 2011. Presentation Type: Abstract Topic: Molecular and cellular neurobiology Citation: Budd JM, Kovács K, Ferecskó AS, Buzás P, Eysel UT and Kisvárday ZF (2011). Wiring Economy of Neocortical Axon Arbors. Front. Neurosci. Conference Abstract: 13th Conference of the Hungarian Neuroscience Society (MITT). doi: 10.3389/conf.fnins.2011.84.00101 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 03 Mar 2011; Published Online: 23 Mar 2011. * Correspondence: Dr. J. M Budd, University of Sussex, School of Informatics, Brighton, United Kingdom, kisvarday@anat.med.unideb.hu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers J. M Budd K. Kovács A. S Ferecskó P. Buzás U. T Eysel Z. F Kisvárday Google J. M Budd K. Kovács A. S Ferecskó P. Buzás U. T Eysel Z. F Kisvárday Google Scholar J. M Budd K. Kovács A. S Ferecskó P. Buzás U. T Eysel Z. F Kisvárday PubMed J. M Budd K. Kovács A. S Ferecskó P. Buzás U. T Eysel Z. F Kisvárday Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Analysis of c-fos and zif268 Expression Reveals Time-Dependent Changes in Activity Inside and Outside the Lesion Projection Zone in Adult Cat Area 17 after Retinal Lesions

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.

Effect of binocular retinal lesions on CRMP2 and CRMP4 but not Dyn I and Syt I expression in adult cat area 17

Removal of retinal input from a restricted region of adult cat visual cortex leads to a substantial reorganization of the retinotopy within the sensory-deprived cortical lesion projection zone (LPZ). Still little is known about the molecular mechanisms underlying this cortical map reorganization. We chose two members of the collapsin response mediator protein (CRMP) family, CRMP2 and CRMP4, because of their involvement in neurite growth, and compared gene and protein expression levels between normal control and reorganizing visual cortex upon induction of central retinal lesions. Parallel analysis of Dynamin I (Dyn I) and Synaptotagmin I (Syt I), two molecules implicated in the exocytosis-endocytosis cycle, was performed because changes in neurotransmitter release have been implicated in cortical plasticity. Western blotting and real-time polymerase chain reaction revealed a clear time-dependent effect of retinal lesioning on CRMP2 and CRMP4 expression, with maximal impact 2 weeks post-lesion. Altered CRMP levels were not a direct consequence of decreased visual activity in the LPZ as complete surgical removal of retinal input to one hemisphere had no effect on CRMP2 or CRMP4 expression. Thus, CRMP expression is correlated to cortical reorganization following partial deafferentation of adult visual cortex. In contrast, Dyn I and Syt I were not influenced and thereby do not promote exocytosis-endocytosis cycle modifications in adult cat cortical plasticity.

Columnar organization of the mammalian visual cortex and its vulnerability following lesion in adult cats

It is well known that in the mammalian visual cortex the neurons, sharing similar response properties, are grouped together into functional units, known as cortical columns. The orientation and ocular dominance columnar organization is a fundamental element for both the anatomical and physiological features of the visual cortex. Nonetheless, little is known about the functional restoration of matured columnar columns following injury. In the present study, the visual cortex of adult cats was studied electrophysiologically, whereas the primary goal of the study was to reveal the functional stability of the columns, disconnected from the main visual input. Experiments were performed on the primary visual cortex (area 17) of 13 anaesthetized and paralyzed adult cats. The columnar distortion was produced by surgical incision perpendicular to the cortical columns. The single unit activity was recorded from 1186 visual cells (experimental groups) in areas proximal and distal to the lesion and, compared to data, received from intact visual cortex (control group). The results indicate that most of the visually responsive cells were found to be selective to specific orientation in all experimental groups (75–100%) similar to the normal control group (78%). Moreover, the distribution of orientation-specific cells was very similar in all experimental and control groups (p > 0.05), as well as in both recording areas (p > 0.05). The percentage of binocular cells was significantly lower in all experimental groups (23–49%) in comparison to the control (80%). However, the distribution of the binocular cells revealed the significant similarity between the experimental and control groups (p > 0.05). An additional finding of the study is that the visual responsiveness of cells was significantly reduced in all experimental groups: only 28–49% of cells were found to be responsive following injury, as compared to 86% in normal control group (p < 0.001). The distribution of cells has also been analysed in accordance with their directional specificity and it has been found that the majority of cells in the experimental groups were found to be bias and non-specific to light stimuli (52–84%) as compared normal controls (21%) (p < 0.001). It has been concluded that, despite the fact that no improvement in visual function was found, the inherent structure of the disrupted cortical columns in the visual cortex was generally preserved. Therefore, the disruption of the columnar connection does not lead to remarkable distortion of the connectivity pattern on the whole, though it does reduce the responsiveness level there. It was concluded that the columnar structure for both orientation and ocular dominance is characterized by high stability, which enables visual processing with minimal brain connections.

Differential display implicates cyclophilin A in adult cortical plasticity.

Removal of retinal input from a restricted region of adult cat visual cortex leads to a substantial reorganization of the retinotopy within the sensory-deprived cortical zone. Little is known about the molecular mechanisms underlying this reorganization. We used differential mRNA display (DDRT-PCR) to compare gene expression patterns between normal control and reorganizing visual cortex (area 17-18), 3 days after induction of central retinal lesions. Systematic screening revealed a decrease in the mRNA encoding cyclophilin A in lesion-affected cortex. In situ hybridization and competitive PCR confirmed the decreased cyclophilin A mRNA levels in reorganizing cortex and extended this finding to longer postlesion survival times as well. Western blotting and immunocytochemistry extended these data to the protein level. In situ hybridization and immunocytochemistry further demonstrated that cyclophilin A mRNA and protein are present in neurons. To exclude the possibility that differences in neuronal activity per se can induce alterations in cyclophilin A mRNA and protein expression, we analyzed cyclophilin A expression in the dorsal lateral geniculate nucleus (dLGN) of retinally lesioned cats and in area 17 and the dLGN of isolated hemisphere cats. In these control experiments cyclophilin A mRNA and protein were distributed as in normal control subjects indicating that the decreased cyclophilin A levels, as observed in sensory-deprived area 17 of retinal lesion cats, are not merely a reflection of changes in neuronal activity. Instead our findings identify cyclophilin A, classically considered a housekeeping gene, as a gene with a brain plasticity-related expression in the central nervous system.

Retinotopic map plasticity in adult cat visual cortex is accompanied by changes in ca 2+/calmodulin-dependent protein kinase ii α autophosphorylation

In adult cats, the induction of homonymous binocular central retinal lesions causes a dramatic reorganization of the topographic map in the sensory-deprived region of the primary visual cortex. To investigate the possible involvement of the α-subunit of the calcium/calmodulin dependent protein kinase type II (αCaMKII) in this form of brain plasticity, we performed in situ hybridization and Western blotting experiments to analyze mRNA, protein and autophosphorylation levels of this multifunctional kinase. No differences in the mRNA or protein levels were observed between the central, sensory-deprived and the peripheral, non-deprived regions of area 17 of retinal lesion animals or between corresponding cortical regions of normal control animals. Western blotting with an αCaMKII threonine-286 phosphorylation-state specific antiserum consistently showed a small, albeit not significant, increase of αCaMKII autophosphorylation in the central versus the peripheral region of cortical area 17, and this both in normal subjects as well as in retinal lesion animals with a 3-day post-lesion survival time. In contrast, a post-lesion survival time of 14 days resulted in a αCaMKII autophosphorylation level that was four times higher in visually-deprived area 17 than in the non-deprived cortical region. This increased phosphorylation state is not a direct consequence of the decrease in visual activity in these neurons, because we would have expected to see a similar change at shorter or longer post-lesion survival times or in the visually deprived visual cortex of animals in which the left optic tract and the corpus callosum were surgically cut. No such changes were observed, leading to the conclusion that the phosphorylation changes observed at 14 days are related to a delayed reorganization of the retinotopic map of the striate cortex.

Reversed-phase high-performance liquid chromatography prefractionation prior to two-dimensional difference gel electrophoresis and mass spectrometry identifies new differentially expressed proteins between striate cortex of kitten and adult cat.

Two-dimensional difference gel electrophoresis (2-D DIGE), in combination with mass spectrometry, is a highly effective method for the rapid and reproducible detection of differentially expressed proteins. This approach, however, has the unfortunate drawback that it preferentially displays rather abundantly expressed proteins. Nevertheless, comparison of the protein expression levels of the striate cortex of adult cats and 30-day-old kittens, resulted in the identification of several proteins related to postnatal brain development and possibly age-dependent plasticity as well (Van den Bergh et al., J. Neurochem. 2003, in press). The goal of the present study was the selective enrichment and identification of less abundant proteins within the same paradigm. Hereto, we performed a reversed-phase chromatography prefractionation of our tissue lysate to separate the proteins in four fractions based on their hydrophobicity prior to 2-D DIGE analysis. This approach not only confirmed the differential expression levels of a number of proteins from the previous study, but also identified three additional proteins preferentially expressed in kitten visual cortex and five additional proteins with higher expression levels in adult cat visual cortex. These spots were not visible on the total tissue lysate protein maps, indicating that the high-performance liquid chromatography (HPLC) prefractionation enabled us to visualize additional, less abundant proteins.

Distribution of the AMPA2 glutamate receptor subunit in adult cat visual cortex

In this study, we revealed the distribution of the AMPA2 glutamate receptor subunit (AMPA2) in the visual cortical areas 17 and 18 of the adult cat by means of different techniques. In situ hybridization, with a cat-specific radioactively labeled oligonucleotide probe, showed that AMPA2 mRNA was expressed mainly in cortical layers II/III and V/VI with a lower expression in layer IV and practically no signal in layer I. Immunocytochemistry, using a polyclonal AMPA2 subunit-specific antibody, showed immunoreactivity almost exclusively in the somata and dendrites of pyramidal neurons in cortical layers II/III and V/VI. Only a very faint signal was detected in layer IV. Neurons with little or no AMPA2 have AMPA receptors that are highly permeable to calcium. By determining the location of AMPA2, this study therefore provides a clear examination of the distribution of Ca 2+-impermeable AMPA receptors over the supra- and infragranular layers of cat visual cortex. The functional implication of the absence of AMPA2 in cortical layer IV and thus the presence of Ca 2+-permeable AMPA receptors in this layer, is still speculative and has yet to be elucidated.

Functional organization of columns in damaged visual cortex of adult cats.

The objective of the present study was to reveal the amount of preservation of the most prominent features of the visual cortex: orientation and ocular dominance columns. It has been assumed that because of its inherent organization, the fragment of cells that would survive following lesioning would preserve the orientation and ocular dominance properties, despite the distortion of the connectivity pattern. The experiments were carried out on 13 anesthetized and paralyzed adult cats from which 1,186 single cells were recorded. The animals were divided into the following three experimental (operated) groups to observe the time lapse of changes after operation: Acute (immediately); Short Chronic (2 to 3 months), and Long Chronic (5 to 7 months). The operations were performed using microsurgical, stereotaxic, electrophysiological, and histological techniques. The disconnection was produced by making a surgical incision into the visual cortex perpendicular to the cortical columns as accurately as possible. The single-unit activity of cells was recorded in the areas proximal and distal to the lesion. In all groups, the visual responsiveness of the cells was significantly reduced and the percentage of binocular cells was significantly lower in all recording sites. The distribution of the cells according to their ocular dominance was similar to that in the normal control group. Surprisingly, most of the cells, that remained visually active, were found selective to orientation in all experimental groups as well as in the normal control group. Even though no improvement in function occurred because mature cells were involved, the inherent structure of the disrupted cortical columns in the visual cortex was preserved. Therefore, the disruption of cortical connections does not lead to remarkable distortion of the inherent connectivity pattern on the whole in visually active cortical fragments.

Plasticity of orientation preference maps in the visual cortex of adult cats.

In contrast to the high degree of experience-dependent plasticity usually exhibited by cortical representational maps, a number of experiments performed in visual cortex suggest that the basic layout of orientation preference maps is only barely susceptible to activity-dependent modifications. In fact, most of what we know about activity-dependent plasticity in adults comes from experiments in somatosensory, auditory, or motor cortex. Applying a stimulation protocol that has been proven highly effective in other cortical areas, we demonstrate here that enforced synchronous cortical activity induces major changes of orientation preference maps (OPMs) in adult cats. Combining optical imaging of intrinsic signals and electrophysiological single-cell recordings, we show that a few hours of intracortical microstimulation (ICMS) lead to an enlargement of the cortical representational zone at the ICMS site and an extensive restructuring of the entire OPM layout up to several millimeters away, paralleled by dramatic changes of pinwheel numbers and locations. At the single-cell level, we found that the preferred orientation was shifted toward the orientation of the ICMS site over a region of up to 4 mm. Our results show that manipulating the synchronicity of cortical activity locally without invoking training, attention, or reinforcement, OPMs undergo large-scale reorganization reminiscent of plastic changes observed for nonvisual cortical maps. However, changes were much more widespread and enduring. Such large-scale restructuring of the visual cortical networks indicates a substantial capability for activity-dependent plasticity of adult visual cortex and may provide the basis for cognitive learning processes.

Cooperative changes in GABA, glutamate and activity levels: the missing link in cortical plasticity.

Different intracortical mechanisms have been reported to contribute to the substantial topographic reorganization of the mammalian primary visual cortex in response to matching lesions in the two retinas: an immediate expansion of receptive fields followed by a gradual shift of excitability into the deprived area and finally axonal sprouting of laterally projecting neurons months after the lesion. To gain insight into the molecular mechanisms of this adult plasticity, we used immunocytochemical and bioanalytical methods to measure the glutamate and GABA neurotransmitter levels in the visual cortex of adult cats with binocular central retinal lesions. Two to four weeks after the lesions, glutamate immunoreactivity was decreased in sensory-deprived cortex as confirmed by HPLC analysis of the glutamate concentration. Within three months normal glutamate immunoreactivity was restored. In addition, the edge of the unresponsive cortex was characterized by markedly increased glutamate immunoreactivity 2-12 weeks postlesion. This glutamate immunoreactivity peak moved into the deprived area over time. These glutamate changes corresponded to decreased spontaneous and visually driven activity in unresponsive cortex and to strikingly increased neuronal activity at the border of this cortical zone. Furthermore, the previously reported decrease in glutamic acid decarboxylase immunoreactivity was found to reflect decreased GABA levels in sensory-deprived cortex. Increased glutamate concentrations and neuronal activity, and decreased GABA concentrations, may be related to changes in synaptic efficiency and could represent a mechanism underlying the retinotopic reorganization that occurs well after the immediate receptive field expansion but long before the late axonal sprouting.

Differential effects of neurotrophins on ocular dominance plasticity in developing and adult cat visual cortex.

In the present study we examine the influence of neurotrophins on experience-dependent synaptic rearrangement in developing and adult visual cortex. Brain-derived neurotrophic factor (BDNF) or nerve growth factor (NGF) was continuously infused into cortical area 18, and the functional architecture of the cortex was examined by use of optical and electrophysiological recording techniques. In kittens, BDNF infusion during monocular deprivation (MD) reversed the normally occurring ocular dominance (OD) shift towards the non-deprived eye so that the deprived eye dominated the BDNF-treated cortex after MD. Under conditions of equal activation of thalamocortical synapses, i.e. when animals were either subject to binocular deprivation (BD) or reared without deprivation, BDNF infusion did not disrupt binocularity of cortical units, but reversed the natural OD bias towards the contralateral eye in favour of the ipsilateral eye. In addition, BDNF treatment in kittens led to a loss of the orientation selectivity of cortical units irrespective of rearing conditions. In adult animals, BDNF influenced neither OD distributions nor orientation selectivity. The effect of NGF was markedly different. It was ineffective in kittens but in adult animals it caused a shift of OD towards the deprived eye when MD was combined with NGF infusion. However, in this case orientation selectivity was preserved. Thus, both neurotrophins have profound activity- and age-dependent effects on the functional architecture of the visual cortex. Moreover, our results indicate that simple substitution of neurotrophins in excess is unlikely to compensate for deprivation effects by preserving or restoring the normal functional architecture of the cortex.

Plasticity in adult cat visual cortex (area 17) following circumscribed monocular lesions of all retinal layers.

1. In eight adult cats intense, sharply circumscribed, monocular laser lesions were used to remove all cellular layers of the retina. The extents of the retinal lesions were subsequently confirmed with counts of alpha-ganglion cells in retinal whole mounts; in some cases these revealed radial segmental degeneration of ganglion cells distal to the lesion. 2. Two to 24 weeks later, area 17 (striate cortex; V1) was studied electrophysiologically in a standard anaesthetized, paralysed (artificially respired) preparation. Recording single- or multineurone activity revealed extensive topographical reorganization within the lesion projection zone (LPZ). 3. Thus, with stimulation of the lesioned eye, about 75 % of single neurones in the LPZ had 'ectopic' visual discharge fields which were displaced to normal retina in the immediate vicinity of the lesion. 4. The sizes of the ectopic discharge fields were not significantly different from the sizes of the normal discharge fields. Furthermore, binocular cells recorded from the LPZ, when stimulated via their ectopic receptive fields, exhibited orientation tuning and preferred stimulus velocities which were indistinguishable from those found when the cells were stimulated via the normal eye. 5. However, the responses to stimuli presented via ectopic discharge fields were generally weaker (lower peak discharge rates) than those to presentations via normal discharge fields, and were characterized by a lower-than-normal upper velocity limit. 6. Overall, the properties of the ectopic receptive fields indicate that cortical mechanisms rather than a retinal 'periphery' effect underlie the topographic reorganization of area 17 following monocular retinal lesions.

Investigation of cortical reorganization in area 17 and nine extrastriate visual areas through the detection of changes in immediate early gene expression as induced by retinal lesions.

The effect of binocular central retinal lesions on the expression of the immediate early genes c-fos and zif268 in the dorsal lateral geniculate nucleus (dLGN) and the visual cortex of adult cats was investigated by in situ hybridization and immunocytochemistry. In the deafferented region of the dLGN, the c-fos mRNA level was decreased within 3 days. The dimensions of the geniculate region showing decreased amounts of c-fos mRNA matched the predictions based on the lesion size and the retinotopic maps of Sanderson ([1971] J. Comp. Neurol. 143:101-118). We did not detect zif268 mRNA in the dLGN. At the cortical level, both c-fos and zif268 mRNA expression decreased in the sensory-deprived region of area 17. In addition, the portions of areas 18, 19, 21a, 21b, and 7, as well as the posterior medial lateral suprasylvian area, the posterior lateral lateral suprasylvian area, the ventral lateral suprasylvian area, and the dorsal lateral suprasylvian area corresponding to the retinal lesions also displayed decreased c-fos and zif268 mRNA levels. Immunocytochemistry revealed similar changes for Zif268 and Fos protein. Three days post lesion, the dimensions of the lesion-affected cortical loci exceeded the predictions in relation to the size of the retinal lesions and the available retinotopic maps. Longer postlesion survival times clearly resulted in a time-dependent restoration of immediate early gene expression from the border to the center of the lesion-affected cortical portions. Our findings represent a new approach for investigating the capacity of adult sensory systems to undergo plastic changes following sensory deprivation and for defining the topographic nature of sensory subcortical and cortical structures.

Restoration of ocular dominance plasticity mediated by adenosine 3',5'-monophosphate in adult visual cortex.

Noradrenaline (NA)-stimulated beta-adrenoreceptors activate adenylate cyclase via excitatory G-proteins (Gs). Activated adenylate cyclase in turn promotes the production of cAMP. Critical roles of cAMP-dependent protein kinase A (PKA) in divergent cellular functions have been shown, including memory, learning and neural plasticity. Ocular dominance plasticity (ODP) is strongly expressed in early postnatal life and usually absent in the mature visual cortex. Here, we asked whether the activation of cAMP-dependent PKA could restore ODP to the aplastic visual cortex of adult cats. Concurrent with brief monocular deprivation, each of the following cAMP-related drugs was directly and continuously infused in the adult visual cortex: cholera toxin (a Gs-protein stimulant), forskolin (a Gs-protein-independent activator of adenylate cyclase) and dibutyryl cAMP (a cAMP analogue). We found that the ocular dominance distribution became W-shaped, the proportion of binocular cells being significantly lower than that in respective controls. We concluded that the activation of cAMP cascades rapidly restores ODP to the adult visual cortex, though moderately. The finding further extends the original hypothesis that the NA-beta-adrenoreceptors system is a neurochemical mechanism of cortical plasticity.

Monocular focal retinal lesions induce short-term topographic plasticity in adult cat visual cortex.

Electrophysiological recording in primary visual cortex (VI) was performed both prior to and in the hours immediately following the creation of a discrete retinal lesion in one eye with an argon laser. Lesion projection zones (LPZs; 21-64 mm2) were defined in the visual cortex by mapping the extent of the lesion onto the topographic representation in cortex. There was no effect on neuronal responses to the unlesioned eye or on its topographic representation. However, within hours of producing the retinal lesion, receptive fields obtained from stimulation of the lesioned eye were displaced onto areas surrounding the scotoma and were enlarged compared with the corresponding field obtained through the normal eye. The proportion of such responsive recording sites increased during the experiment such that 8-11 hours post-lesion, 56% of recording sites displayed neurons responsive to the lesioned eye. This is an equivalent proportion to that previously reported with long-term recovery (three weeks to three months). Responsive neurons were evident as far as 2.5 mm inside the border of the LPZ. The reorganization of the lesioned eye representation produced binocular disparities as great as 15 degrees, suggesting interactions between sites in VI up to 5.5 mm apart.

Increased receptive field size in the surround of chronic lesions in the adult cat visual cortex.

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.