Reversal of the physiological effects of monocular deprivation in the kitten's visual cortex.

1. Twenty-three kittens were monocularly deprived of vision until the age of 4, 5, 6 or 7 weeks. Their deprived eyes were then opened, and their experienced eyes shut for a further 3-63 days. After this time physiological recordings were made in the visual cortex, area 17. Three control kittens, monocularly deprived for various periods, showed that at the time of reverse-suturing, few neurones could be influenced at all from the deprived eye. 2. Following reverse-suturing, the initially deprived eye regained control of cortical neurones. This switch of cortical ocular dominance was most rapid following reverse-suturing at the age of 4 weeks. Delaying the age of reverse-suturing reduced the rate and then the extent of the cortical ocular dominance changes. 3. The cortex of reverse-sutured kittens is divided into regions of cells dominated by one eye or the other. The relative sizes of these ocular dominance columns changed during reversed deprivation. The columns devoted to the initially deprived eye were very small in animals reverse-sutured for brief periods, but in animals that underwent longer periods of reversed deprivation, the columns driven by that eye were larger, while those devoted to the initially open eye were smaller. 4. Clear progressions of orientation columns across the cortex were apparent in many of the kittens, but, in contrast to the situation in normal or strabismic kittens, these sequences were disrupted at the borders of eye dominance columns: the cortical representations of orientation and ocular dominance were not independent. 5. Binocular units in these kittens were rather rare, but those that could be found often had dissimilar receptive field properties in the two eyes. Commonly, a cell would have a normal orientation selective receptive field in one eye, and an immature, unselective receptive field in the other. Cells that had orientation selective receptive fields in both eyes often had greatly differing orientation preferences in the two eyes, occasionally by nearly 90 degrees. 6. During the reversal of deprivation effects, the proportion of receptive fields exhibiting mature properties declined in the initially experienced eye, while the proportion increased in the initially deprived eye. Similarly, the average band width of orientation tuning of receptive fields in the initially deprived eye decreased, while that of receptive fields in the initially experienced eye increased. 7. One kitten was reverse-sutured twice, to demonstrate that cortical ocular dominance may be reversed a second time, even after one reversal of ocular dominance. 8. It is suggested that the sensitive period for cortical binocular development consists of two phases. In the first phase, all cortical neurones may be modified by experience, but the rate at which they may be modified decreases with age. In the second phase, an increasing number of cortical neurones becomes fixed in their properties, while those that remain modifiable are as modifiable as they were at the end of the first phase. 9...     

Central core control of developmental plasticity in the kitten visual cortex: II. Electrical activation of mesencephalic and diencephalic projections

Summary Fifteen dark-reared, 4- to 5-week-old kittens were stimulated monocularly with patterned light while they were anesthetized and paralyzed. Six of these kittens were exposed to the light stimuli only, in four kittens the light stimuli were paired with electric stimulation of the mesencephalic reticular formation and in five kittens with electric activation of the medial thalamic nuclei. Throughout the conditioning period, the ocular dominance of neurons in the visual cortex was determined from evoked potentials that were elicited either with electric stimulation of the optic nerves or with phase reversing gratings of variable spatial frequencies. In two kittens, ocular dominance changes were assessed after the end of the conditioning period by analyzing single unit receptive fields. Monocular stimulation with patterned light induced a marked shift of ocular dominance toward the stimulated eye, when the light stimulus was paired with electric activation of either the mesencephalic reticular formation or of the medial thalamus. Moreover, a substantial fraction of cells acquired mature receptive fields. No such changes occurred with light or electric stimulation alone. It is concluded that central core projections which modulate cortical excitability gate experience-dependent modifications of connections in the kitten visual cortex.Part of this work was supported by a grant from the Deutsche Forschungsgemeinschaft SFB50, A14     

Expression of the transcription factor Zif268 in the visual cortex of monocularly deprived rats: effects of nerve growth factor.

Neurotrophins are known to be involved in experience-dependent plasticity of the visual cortex. Here, we have characterized in detail the effects of intraventricular nerve growth factor infusion in monocularly deprived rats by using immunostaining for the immediate-early gene product Zif268 as a marker of functional activity with cellular resolution. We have taken advantage of the rapid regulation of Zif268 by visual input to reveal the cortical units that are responsive to the deprived eye after a period of monocular deprivation. We found that responses to the deprived eye were significantly preserved in the cortex of monocularly deprived rats infused with nerve growth factor. The effects of nerve growth factor were greater for cortical cells located in deep layers and with more peripheral receptive fields. Results from Zif268 staining correlated very well with those obtained by single-cell recordings from the visual cortex. Our results demonstrate that exogenous nerve growth factor preserves the functional input from the deprived eye, enabling cortical neurons to activate immediate-early gene expression in response to stimulation of the deprived eye. Furthermore, we show that the intraventricular infusion of nerve growth factor differentially affects the ocular dominance of cells at various depths and eccentricities in the developing cortex.     

Infusion of nerve growth factor (NGF) into kitten visual cortex increases immunoreactivity for NGF, NGF receptors, and choline acetyltransferase in basal forebrain without affecting ocular dominance plasticity or column development.

Intracerebroventricular or intracortical administration of nerve growth factor (NGF) has been shown to block or attenuate visual cortical plasticity in the rat. In cats and ferrets, the effects of exogenous NGF on development and plasticity of visual cortex have been reported to be small or nonexistent. To determine whether locally delivered NGF affects ocular dominance column formation or the plasticity produced by monocular deprivation in cats at the height of the critical period, we infused recombinant human NGF into the primary visual cortex of kittens using an implanted cannula minipump. NGF had no effect on the normal developmental segregation of geniculocortical afferents into ocular dominance columns as determined both physiologically and anatomically. The plasticity of binocular visual cortical responses induced by monocular deprivation was also normal in regions of immunohistochemically detectable NGF infusion, as measured using intrinsic signal optical imaging and single-unit electrophysiology. Immunohistochemical analysis of the basal forebrain regions of the same animals demonstrated that the NGF infused into cortex was biologically active, producing an increase in the number of NGF-, TrkA-, p75(NTR)-, and choline acetyltransferase-positive neurons in basal forebrain nuclei in the hemisphere ipsilateral to the NGF minipump compared to the contralateral basal forebrain neurons.We conclude that NGF delivered locally to axon terminals of cholinergic basal forebrain neurons resulted in increases in protein expression at the cell body through retrograde signaling.     

Development of orientation tuning in simple cells of primary visual cortex

Orientation selectivity and its development are basic features of visual cortex. The original model of orientation selectivity proposes that elongated simple cell receptive fields are constructed from convergent input of an array of lateral geniculate nucleus neurons. However, orientation selectivity of simple cells in the visual cortex is generally greater than the linear contributions based on projections from spatial receptive field profiles. This implies that additional selectivity may arise from intracortical mechanisms. The hierarchical processing idea implies mainly linear connections, whereas cortical contributions are generally considered to be nonlinear. We have explored development of orientation selectivity in visual cortex with a focus on linear and nonlinear factors in a population of anesthetized 4-wk postnatal kittens and adult cats. Linear contributions are estimated from receptive field maps by which orientation tuning curves are generated and bandwidth is quantified. Nonlinear components are estimated as the magnitude of the power function relationship between responses measured from drifting sinusoidal gratings and those predicted from the spatial receptive field. Measured bandwidths for kittens are slightly larger than those in adults, whereas predicted bandwidths are substantially broader. These results suggest that relatively strong nonlinearities in early postnatal stages are substantially involved in the development of orientation tuning in visual cortex.     

Development of spatial receptive-field organization and orientation selectivity in kitten striate cortex

The functional organization of the receptive field of neurons in striate cortex of kittens from 8 days to 3 mo of age was studied by extracellular recordings. A quantitative dual-stimulus technique was used, which allowed for analysis of both enhancement and suppression zones in the receptive field. Furthermore the development of orientation selectivity was studied quantitatively in the same cells. Already in the youngest kittens the receptive fields were spatially organized like adult fields, with a central zone and adjacent flanks that responded in opposite manner to the light stimulus. The relative suppression in the subzones was as strong as in adult cells. Both simple and complex cells were found from 8 days. The receptive fields were like magnified adult fields. The width of the dominant discharge-field zone and the distance between the positions giving maximum discharge and maximum suppression decreased with age in the same proportions. The decrease could be explained by a corresponding decrease of the receptive-field-center size of retinal ganglion cells. Forty percent of the cells were orientation selective before 2 wk, and the fraction increased to 94% at 4 wk. Cells whose responses could be attenuated to at least half of the maximal response by changes of slit orientation were termed orientation selective. The half-width of the orientation-tuning curves narrowed during the first 5 wk, and this change was most marked in simple cells. The ability of the cells to discriminate between orientations in statistical terms was weak in the youngest kittens due to a large response variability, and showed a more pronounced development than the half-width did. The orientation-tuning curves were fitted by an exponential function, which showed the shape to be adultlike in all age groups. Two kittens were dark reared until recording at 1 mo of age. The spatial receptive-field organization and the orientation selectivity in these kittens were similar to normal-reared kittens at 1 mo. The responsivity of the cells of the dark-reared kittens was lower, and the latency before firing was longer than in the normal-reared kittens of the same age, and these response properties were more similar to those in 1- to 2-wk-old normal kittens. Our results indicate that the spatial organization of the receptive field is innate in most cells and that visual experience is unnecessary for the organization to be maintained and for the receptive-field width to mature during the first month postnatally.(ABSTRACT TRUNCATED AT 400 WORDS)     

Possible role of S-100 in glia—Neuronal signalling involved in activity-dependent plasticity in the developing mammalian cortex

Using Western blot analyses and a quantitative ELISA, we identified the presence and developmental accumulation of the astroglial S-100 protein(s) in rat and cat visual cortex. There is a steep rise in the S-100 content, comprising mainly S-100β, during the time period of highest cortical malleability in both species. A possible role of the astroglial S-100 protein(s) in experience-dependent plasticity of the visual cortex of kittens was tested by infusing antiserum against this protein during the critical period for cortical malleability. Following 1 week of monocular deprivation, the ocular dominance of single cells in the visual cortex was investigated. The vast majority of cells in the hemispheres infused with anti-S-100 serum maintained binocular responses. This finding suggests that extracellular S-100 protein is essential for ocular-dominance plasticity. Infusion of S-100β during the critical period of cortical malleability had no effect on deprivation-induced ocular-dominance plasticity, but interfered with the experience-dependent refinement of orientation selectivity of visual cortical neurons. It is suggested that S-100β may play an important role in the refinement of cortical circuitries by selectively affecting active or activated neuronal compartments. As S-100β is synthesized in astroglial cells, the effects on neuronal plasticity imply that glia-neuronal information transfer occurs during activity-dependent plasticity. Possible underlying mechanisms are discussed on the basis of current knowledge on the S-100 protein family, especially S-100β (Marshak, 1990).     

Coding of tactile response properties in the rat deep cerebellar nuclei

In the lateral hemispheres of the cerebellar cortex, somatosensory responses are represented in a finely grained fractured somatotopy. It is unclear, however, how these responses contribute to the ultimate output of the cerebellum from the deep cerebellar nuclei (DCN). Robust responses of DCN neurons to somatosensory stimuli have been described, but a detailed examination of their somatotopic arrangement and stimulus coding properties is lacking. To address these questions, we recorded extracellular, single-unit activity in the DCN of ketamine-anesthetized rats in response to air-puff stimuli aimed at six different orofacial and forelimb locations. In additional experiments, the duration and intensity of air-puff stimuli to the ipsilateral upper lip were systematically varied. Overall, we found that DCN neuron responses to air puff stimuli showed combinations of three distinct response components: a short-latency spike response, a pronounced inhibition, and a long-latency increase in firing. Individual neurons responsive to air-puff stimulation exhibited any combination of just one, two, or all three of these response components. The inhibitory response was most common and frequently consisted of a complete cessation of spiking despite a high spontaneous rate of baseline firing. In contrast to published findings from cerebellar cortical recordings, the receptive fields of all responsive neurons in the DCN were large. In fact, the receptive field of most neurons covered the ipsi- and contralateral face as well as forepaws. Response properties of individual neurons did not reliably indicate stimulus intensity or duration, although as a population DCN neurons showed significantly increasing response amplitudes as air-puff intensity or duration increased. Overall, the responses were characterized by a distinct temporal profile in each neuron, which remained unchanged with changes in stimulus condition. We conclude that the responses in the DCN of rats to air-puff stimuli differ substantially from cerebellar cortical responses in their receptive field properties and do not provide a robust code of tactile stimulus properties. Rather, the characteristic temporal response profile of each neuron may be tuned to control the timing of a specific task to which its output is linked.     

Reduced binocularity in the noradrenaline-infused striate cortex of acutely anesthetized and paralyzed,otherwise normal cats

Summary In anesthetized and paralyzed cats, the normal alignment of the visual axes is disturbed by paralysis of the eye muscles. Thus, the separation between paired receptive fields of binocular cells in visual cortex is increased (paralysis squint). This increased separation is normally tolerated by the majority of visuocortical cells, about 80% of them being binocularly driven (Hubel and Wiesel 1962). It was shown previously that neuronal plasticity in visual cortex can be enhanced in both normal adult cats (Kasamatsu et al. 1979) and kittens (Kuppermann and Kasamatsu 1984) by intracortical microinfusion of noradrenaline (NA). In the present study we tested whether the usual range of disparity produced by the paralysis squint is sufficient to induce ocular dominance changes in visual cortex of adult cats when the neuronal plasticity is enhanced by NA. NA was continuously infused into visual cortex throughout the experiments. The period of the paralysis squint varied from experiment to experiment between 9 and 47 h. We found: (1) These short periods were sufficient to produce a marked reduction in the proportion of binocular cells. (2) The proportion decreased linearly with increasing the duration of the squint period at a rate of 0.17 per 10 h up to about 22 h. (3) At longer durations the average binocularity remained at about 0.30 and could not be further reduced in the present paradigm. (4) The binocularity seemed to decrease with increasing separation of paired receptive fields. (5) Binocularity increased again toward the normal value after optical correction of the squint. (6) The amount of increased binocularity was linearly correlated with the duration of the period after the squint correction. (7) The binocularity increased at a rate of 0.18 per 10 h, reaching the normal value in less than 30 h. We thus concluded that if visuocortical plasticity is maintained at a high level through the continuous infusion of NA it is possible to change the ocular dominance distribution in the mature visual cortex by manipulations of the alignment of the visual axes even in the acutely anesthetized and paralyzed condition.     

Functional organization of the cortical 17/18 border region in the cat

Summary The representation of the visual field in the 17/18 border region of the cat's visual cortex, and the layout of orientation and ocular dominance columns, were studied by making many closely spaced electrode penetrations into the superficial layers of the flattened dorsal region of the marginal gyrus and recording response properties at each location. The 17/18 border region was defined by measuring the change in the horizontal component of receptive field position within the gyrus: as the position of the recording electrode moved from medial to lateral, the receptive fields moved towards the vertical midline, indicating that the electrode was in area 17; as penetrations were made in increasingly lateral positions, the trend reversed, and receptive field positions moved away from the midline, indicating that the electrode was in area 18. The receptive fields of cells close to the border straddled, or lay within 2°–3° on either side of the vertical midline. In addition, patches of cortex were sometimes encountered in which cells had receptive field centers located up to 7° in the ipsilateral visual field. Experiments in which maps were made in the left and right hemispheres of a single animal showed that these patches had a complementary distribution in the two hemispheres. Cells within the patches behaved as though driven by Y-cell inputs: they usually had large receptive fields and responded to rapidly-moving stimuli. They were broadly tuned for orientation and strongly dominated by the contralateral eye. Fourier spectral analysis of orientation selectivity maps showed that iso-orientation bands had an average spacing of 1.14 ± 0.1 mm and tended to be elongated in a direction orthogonal to the 17/18 border. Individual bands crossed the border without obvious interruption, although singularities (points of discontinuity in the layout of orientations) were more frequently observed in the border region than in adjacent areas. Two dominant periodicities could be measured in the maps of ocular dominance, one at around 0.8 ± 0.2 mm and a second at 2.0 ± 0.3 mm. No constant direction of elongation was noted. These are close to the periods present within areas 17 and 18 respectively.     

Functional organization of the cortical 17/18 border region in the cat

The representation of the visual field in the 17/18 border region of the cat's visual cortex, and the layout of orientation and ocular dominance columns, were studied by making many closely spaced electrode penetrations into the superficial layers of the flattened dorsal region of the marginal gyrus and recording response properties at each location. The 17/18 border region was defined by measuring the change in the horizontal component of receptive field position within the gyrus: as the position of the recording electrode moved from medial to lateral, the receptive fields moved towards the vertical midline, indicating that the electrode was in area 17; as penetrations were made in increasingly lateral positions, the trend reversed, and receptive field positions moved away from the midline, indicating that the electrode was in area 18. The receptive fields of cells close to the border straddled, or lay within 2 degrees-3 degrees on either side of the vertical midline. In addition, patches of cortex were sometimes encountered in which cells had receptive field centers located up to 7 degrees in the ipsilateral visual field. Experiments in which maps were made in the left and right hemispheres of a single animal showed that these patches had a complementary distribution in the two hemispheres. Cells within the patches behaved as though driven by Y-cell inputs: they usually had large receptive fields and responded to rapidly-moving stimuli. They were broadly tuned for orientation and strongly dominated by the contralateral eye. Fourier spectral analysis of orientation selectivity maps showed that iso-orientation bands had an average spacing of 1.14 +/- 0.1 mm and tended to be elongated in a direction orthogonal to the 17/18 border. Individual bands crossed the border without obvious interruption, although singularities (points of discontinuity in the layout of orientations) were more frequently observed in the border region than in adjacent areas. Two dominant periodicities could be measured in the maps of ocular dominance, one at around 0.8 +/- 0.2 mm and a second at 2.0 +/- 0.3 mm. No constant direction of elongation was noted. These are close to the periods present within areas 17 and 18 respectively.     

Central core control of developmental plasticity in the kitten visual cortex: I. Diencephalic lesions

Summary In five, dark-reared, 4-week-old kittens the posterior two thirds of the corpus callosum were split, and a lesion comprising the intralaminar nuclei was made of the left medial thalamic complex. In addition, the right eye was closed by suture. Postoperatively, the kittens showed abnormal orienting responses, neglecting visual stimuli presented in the hemifield contralateral to the side of the lesion. Sudden changes in light, sound, or somatosensory stimulation elicited orienting responses that all tended toward the side of the lesion. These massive symptoms faded within a few weeks but the kittens continued to neglect visual stimuli in the hemifield contralateral to the lesion when a second stimulus was presented simultaneously in the other hemifield. Electrophysiologic analysis of the visual cortex, performed after the end of the critical period, revealed marked interhemispheric differences. In the visual cortex of the normal hemisphere most neurons were monocular and responded exclusively to stimulation of the open eye, but otherwise had normal receptive field properties. In the visual cortex of the hemisphere containing the thalamic lesion, the majority of the neurons remained binocular. In addition, the selectivity for stimulus orientation and the vigor of responses to optimally aligned stimuli were subnormal on this side. Thus, the same retinal signals, which in the control hemisphere suppressed the pathways from the deprived eye and supported the development of normal receptive fields, failed to do either in the hemisphere containing the thalamic lesion. Apparently, experience-dependent changes in the visual cortex require both retinal stimulation and the functioning of diencephalic structures which modulate cortical excitability and control selective attention.     

Cortical activity blockade prevents ocular dominance plasticity in the kitten visual cortex

Summary Recordings from single units in kitten primary visual cortex show that a reversible blockade of the discharge activities of cortical neurons and geniculocortical afferent terminals by intracortical infusion of the sodium channel blocker tetrodotoxin (TTX) completely prevented the ocular dominance shift that would normally be seen after monocular deprivation. The blockade of cortical plasticity, like the blockade of discharge activity, was reversible, and plasticity was restored following recovery from the effects of TTX. These results extend previous work suggesting involvement of electrical activity at the level of the cortex in the phenomenon of cortical plasticity by demonstrating an absolute requirement for discharge activities in the primary visual cortex.This work was supported by the NIH (EY02874 and EY00213) and by grants from the March of Dimes Birth Defects Foundation and the University of California Academic Senate     

Intracortical pathways determine breadth of subthreshold frequency receptive fields in primary auditory cortex

To examine the basis of frequency receptive fields in auditory cortex (ACx), we have recorded intracellular (whole cell) and extracellular (local field potential, LFP) responses to tones in anesthetized rats. Frequency receptive fields derived from excitatory postsynaptic potentials (EPSPs) and LFPs from the same location resembled each other in terms of characteristic frequency (CF) and breadth of tuning, suggesting that LFPs reflect local synaptic (including subthreshold) activity. Subthreshold EPSP and LFP receptive fields were remarkably broad, often spanning five octaves (the maximum tested) at moderate intensities (40-50 dB above threshold). To identify receptive-field features that are generated intracortically, we microinjected the GABA(A) receptor agonist muscimol (0.2-5.1 mM, 1-5 microl) into ACx. Muscimol dramatically reduced LFP amplitude and reduced receptive-field bandwidth, implicating intracortical contributions to these features but had lesser effects on CF response threshold or onset latency, suggesting minimal loss of thalamocortical input. Reversal of muscimol's inhibition preferentially at the recording site by diffusion from the recording pipette of the GABA(A) receptor antagonist picrotoxin (0.01-100 microM) disinhibited responses to CF stimuli more than responses to spectrally distant, non-CF stimuli. We propose that thalamocortical and intracortical pathways preferentially contribute to responses evoked by CF and non-CF stimuli, respectively, and that intracortical projections linking frequency representations determine the breadth of receptive fields in primary ACx. Broad, subthreshold receptive fields may distinguish ACx from subcortical auditory relay nuclei, promote integrated responses to spectrotemporally complex stimuli, and provide a substrate for plasticity of cortical receptive fields and maps.     

Network architecture, receptive fields, and neuromodulation: computational and functional implications of cholinergic modulation in primary auditory cortex

Two fundamental issues in auditory cortical processing are the relative importance of thalamocortical versus intracortical circuits in shaping response properties in primary auditory cortex (ACx), and how the effects of neuromodulators on these circuits affect dynamic changes in network and receptive field properties that enhance signal processing and adaptive behavior. To investigate these issues, we developed a computational model of layers III and IV (LIII/IV) of AI, constrained by anatomical and physiological data. We focus on how the local and global cortical architecture shape receptive fields (RFs) of cortical cells and on how different well-established cholinergic effects on the cortical network reshape frequency-tuning properties of cells in ACx. We identify key thalamocortical and intracortical circuits that strongly affect tuning curves of model cortical neurons and are also sensitive to cholinergic modulation. We then study how differential cholinergic modulation of network parameters change the tuning properties of our model cells and propose two different mechanisms: one intracortical (involving muscarinic receptors) and one thalamocortical (involving nicotinic receptors), which may be involved in rapid plasticity in ACx, as recently reported in a study by Fritz and coworkers.     

Short exposure to an enriched environment accelerates plasticity in the barrel cortex of adult rats

Cortical sensory neurons adapt their response properties to use and disuse of peripheral receptors in their receptive field. Changes in synaptic strength can be generated in cortex by simply altering the balance of input activity, so that a persistent bias in activity levels modifies cortical receptive field properties. Such activity-dependent plasticity in cortical cell responses occurs in rat cortex when all but two whiskers are trimmed for a period of time at any age. The up-regulation of evoked responses to the intact whiskers is first seen within 24 h in the supragranular layers [Laminar comparison of somatosensory cortical plasticity. Science 265(5180):1885-1888] and continues until a new stable state is achieved [Experience-dependent plasticity in adult rat barrel cortex. Proc Natl Acad Sci U S A 90(5):2082-2086; Armstrong-James M, Diamond ME, Ebner FF (1994) An innocuous bias in whisker use in adult rat modifies receptive fields of barrel cortex neurons. J Neurosci 14:6978-6991]. These and many other results suggest that activity-dependent changes in cortical cell responses have an accumulation threshold that can be achieved more quickly by increasing the spike rate arising from the active region of the receptive field. Here we test the hypothesis that the rate of neuronal response change can be accelerated by placing the animals in a high activity environment after whisker trimming. Test stimuli reveal an highly significant receptive field bias in response to intact and trimmed whiskers in layer IV as well as in layers II-III neurons in only 15 h after whisker trimming. Layer IV barrel cells fail to show plasticity after 15-24 h in a standard cage environment, but produce a response bias when activity is elevated by the enriched environment. We conclude that elevated activity achieves the threshold for response modification more quickly, and this, in turn, accelerates the rate of receptive field plasticity.     

Blockade of serotonin-2C receptors by mesulergine reduces ocular dominance plasticity in kitten visual cortex

 We have investigated the role of serotonin-2C (5-HT_2C) receptors in modulation of ocular dominance plasticity in kitten visual cortex. A small quantity of the 5-HT_2C receptor blocker, mesulergine, was infused into the visual cortex of one hemisphere of 5- to 7-week-old kittens using osmotic minipumps, while the control hemisphere received vehicle solution. At the same time, one eyelid of the experimental animals was sutured shut. The ocular dominance distributions in the visual cortex (area 17) were assessed using extracellular recording methods after 1 week of combined mesulergine infusion and monocular deprivation. We found that the majority of the neurons remained binocularly responsive in the mesulergine-treated hemisphere, while most of the neurons recorded were either unresponsive or only weakly responsive to the deprived eye in the control hemisphere. Local infusion of mesulergine into the kitten visual cortex thus reduced the shift of ocular dominance that normally occurs in animals of these ages following monocular deprivation. The blocking effect seems to be distance-dependent and therefore dose-dependent: the farther away the recording sites were from the injection site, the fewer binocularly responsive cells were found. These results are relevant to previous findings indicating transient overexpression of 5-HT_2C receptor in visual cortex of kittens at these ages. The data suggest that the 5-HT_2C receptor system may be involved in the formation and modification of ocular dominance columns in the developing visual cortex. Received: 11 December 1995 / Accepted: 9 June 1996     

Ocular dominance plasticity restored by NA infusion to aplastic visual cortex of anesthetized and paralyzed kittens

Summary We studied the ocular dominance distribution in visual cortex of kittens which had been monocularly exposed to moving-pattern stimuli under anesthesia and paralysis. 1. We did not obtain any discernible changes in ocular dominance, confirming the previous reports that anesthesia and paralysis prevent ocular dominance plasticity from occurring. 2. The plasticity, however, was restored under the acute experimental condition by a cortical infusion of 1-noradrenaline (1-NA). In the 1-NA-infused visual cortex, the ocular dominance distribution was clearly shifted to the open eye after monocular exposure for about 20–24 h. 3. We also studied how quickly and to what extent the changes were induced when the duration of the combined treatment was varied. The results were: (i) the earliest change was observed in 12 h with disappearance of binocular cells, (ii) the treatment was most effective after 20–24 h in inducing the shift of ocular dominance, and (iii) the treatment longer than 24 h (up to 45 h) did not necessarily enhance the shift, though the state of reduced binocularity was sustained throughout. 4. The effects of the cortical 1-NA infusion combined with monocular exposure became less with increasing the age of experimental animals, suggesting the presence of the susceptible period in the acute experiments. 5. The effects seemed to become smaller toward the end of a given recording session, suggesting that the restored plasticity wanes with time. The present results further support the idea that the direct activation of the NA system enhances cortical plasticity, in principle, independent of general conditions of experimental animals.     

Effects of monocular deprivation on the expression pattern of alpha-1 and beta-1 adrenergic receptors in the kitten visual cortex

To examine how adrenergic receptors are regulated by experimental manipulation of sensory afferents, we performed immunohistochemical analysis on alpha1-, and beta1-adrenergic receptors in the brain of kittens. In normal development, these receptors were similarly expressed in both hemispheres of the occipital and frontal cortices. Notably, monocular deprivation during the sensitive period of ocular dominance plasticity significantly increased beta1-adrenergic receptor immunoreactivity in the visual cortex ipsilateral to the deprived eye. No increase in the intensity of the immunoreactivity for beta1-adrenergic receptors following monocular deprivation was found in the frontal and parietal regions of the cerebral cortex and subcortical structures, including the lateral geniculate nucleus and superior colliculus. Furthermore, such hemispheric change was not found in the alpha1-adrenergic receptor immunoreactivity following monocular deprivation. Comparisons of images, obtained by double staining for microtubule-associated protein-2 or glial fibrillary acidic protein, indicated that the increased immunoreactivity was localized on both apical dendrites of deep layer neurons and glial cells. These results indicate that the monocular deprivation during the sensitive period of ocular dominance plasticity modified beta1-adrenergic receptor immunoreactivity, including that in glial cells. Therefore, it was suggested that beta1-adrenergic receptors in the glial cells also play important roles in the regulation of ocular dominance plasticity.     

The effect of visual experience on the development of stimulus specificity by kitten cortical neurones

1. 284 single cortical neurones were studied in area seventeen of twenty-five normal kittens and of fifteen kittens, binocularly deprived, whose first visual experience had been delayed until the experiment by bilateral lid-suture. Both normal and binocularly deprived kittens ranged in age from 1 to 6 weeks.2. The optimal, binocularly presented, visual stimulus and receptive fields were determined for each neurone by varying target configuration, speed and direction of movement and the prism-induced alignment of both eyes. Repetitive, controlled stimulation in eighty-four cases allowed quantitative estimates to be made of the response selectivity for the target configuration (spot vs. line), the direction of target motion and the prism-induced disparity between the retinal images of the binocular target.3. Before the fourth post-natal week neurones from both normal and binocularly deprived cortex showed similar properties: selectivity for direction of target motion was present in both preparations but both lacked binocular specificity and dependence on target configuration.4. After the fourth week, normal kittens had increasing numbers of neurones with selective responses which were dependent upon target configuration and the degree of binocular misalignment. The proportion of selective neurones approached the adult value after the fifth week.5. The cortex of binocularly deprived kittens failed to show an increase of selectivity with age, and of 150 neurones, sixty-two were visually unresponsive, two showed selectivity which was dependent upon target configuration and none showed selectivity for prism-induced retinal disparity.6. The data are not consistent with the hypothesis that the highly specific response properties of visual cortical neurones can develop without appropriate visual experience. Innate mechanisms appear to be sufficient for the development of the excitatory connexions producing motion sensitivity and receptive field location on both retinas, but patterned visual experience is necessary for the ;fine-tuning' which vetoes responses to stimuli with non-optimal configuration or binocular disparity.