Experience-dependent plasticity in adult visual cortex

Experience-dependent plasticity is a prominent feature of the mammalian visual cortex. Although such neural changes are most evident during development, adult cortical circuits can be modified by a variety of manipulations, such as perceptual learning and visual deprivation. Elucidating the underlying mechanisms at the cellular and synaptic levels is an essential step in understanding neural plasticity in the mature animal. Although developmental and adult plasticity share many common features, notable differences may be attributed to developmental cortical changes at multiple levels. These range from shifts in the molecular profiles of cortical neurons to changes in the spatiotemporal dynamics of network activity. In this review, we will discuss recent progress and remaining challenges in understanding adult visual plasticity, focusing on the primary visual cortex.     

Simulation of plasticity in the adult visual cortex

 Retinal plasticity has been shown in the adult visual nervous system in mammals. Following a retinal lesion (scotoma) there is a reorganization of the cortical receptive field distribution: cortical neurons selective to visual stimuli in the area of the visual field corresponding to the retinal lesion, become selective to other parts of the visual field. In this work, we study this effect with a self-organizing neural network. In a first stage, the network reaches a pattern of connectivity that represents normal development of neuronal selectivity. The scotoma is simulated by perturbing accordingly the properties of a region of the input layer representing the retina. The system evolves to a new receptive field distribution mainly by means of the reorganization of the intra cortical connectivity. No major change of the geniculo cortical connectivity is detected. This may explain the surprisingly short time scale of the event. Received: 6 June 2000 / Accepted in revised form: 16 October 2000     

How the mechanisms of long-term synaptic potentiation and depression serve experience-dependent plasticity in primary visual cortex

Donald Hebb chose visual learning in primary visual cortex (V1) of the rodent to exemplify his theories of how the brain stores information through long-lasting homosynaptic plasticity. Here, we revisit V1 to consider roles for bidirectional ‘Hebbian’ plasticity in the modification of vision through experience. First, we discuss the consequences of monocular deprivation (MD) in the mouse, which have been studied by many laboratories over many years, and the evidence that synaptic depression of excitatory input from the thalamus is a primary contributor to the loss of visual cortical responsiveness to stimuli viewed through the deprived eye. Second, we describe a less studied, but no less interesting form of plasticity in the visual cortex known as stimulus-selective response potentiation (SRP). SRP results in increases in the response of V1 to a visual stimulus through repeated viewing and bears all the hallmarks of perceptual learning. We describe evidence implicating an important role for potentiation of thalamo-cortical synapses in SRP. In addition, we present new data indicating that there are some features of this form of plasticity that cannot be fully accounted for by such feed-forward Hebbian plasticity, suggesting contributions from intra-cortical circuit components.     

Sleep enhances plasticity in the developing visual cortex

During a critical period of brain development, occluding the vision of one eye causes a rapid remodeling of the visual cortex and its inputs. Sleep has been linked to other processes thought to depend on synaptic remodeling, but a role for sleep in this form of cortical plasticity has not been demonstrated. We found that sleep enhanced the effects of a preceding period of monocular deprivation on visual cortical responses, but wakefulness in complete darkness did not do so. The enhancement of plasticity by sleep was at least as great as that produced by an equal amount of additional deprivation. These findings demonstrate that sleep and sleep loss modify experience-dependent cortical plasticity in vivo. They suggest that sleep in early life may play a crucial role in brain development.     

Cortisol reduces plasticity in the kitten visual cortex

We investigated the effect of elevated levels of cortisol on plasticity in the visual cortex of the cat. Animals were given daily injections of cortisol i.m. for 20 days starting around 35 days of age. After 10 days they were monocularly deprived, and after an additional 10 days recordings were made from the visual cortex to construct an ocular dominance histogram. The results were compared with those from normal animals of the same age, and with animals monocularly deprived for the same period but not treated with cortisol. Cortisol reduced the ocular dominance shift in a dose-dependent manner, but did not totally abolish it even at the highest doses used. Two other series of animals were recorded, one slightly later in the critical period and one slightly earlier, with care taken to give cortisol before the animals were exposed to light in the morning. In both cases, cortisol reduced the ocular dominance shift but did not abolish it. To interpret these results, we measured levels of plasma cortisol in normal cats of various ages. Average levels were fairly constant between birth and 12 months of age (0.5–1 μg/dl), and increased slightly after that, but there was a large variation between animals. Thus elevated levels of cortisol can have a substantial effect on plasticity in the visual cortex of the cat, but the decline of the critical period for plasticity between 6 weeks and 3–5 months of age does not seem to be due to a rise in cortisol levels during this time.     

Genetic control of experience-dependent plasticity in the visual cortex

Depriving one eye of visual experience during a sensitive period of development results in a shift in ocular dominance (OD) in the primary visual cortex (V1). To assess the heritability of this form of cortical plasticity and identify the responsible gene loci, we studied the influence of monocular deprivation on OD in a large number of recombinant inbred mouse strains derived from mixed C57BL/6J and DBA/2J backgrounds (BXD). The strength of imaged intrinsic signal responses in V1 to visual stimuli was strongly heritable as were various elements of OD plasticity. This has important implications for the use of mice of mixed genetic backgrounds for studying OD plasticity. C57BL/6J showed the most significant shift in OD, while some BXD strains did not show any shift at all. Interestingly, the increase in undeprived ipsilateral eye responses was not correlated to the decrease in deprived contralateral eye responses, suggesting that the size of these components of OD plasticity are not genetically controlled by only a single mechanism. We identified a quantitative trait locus regulating the change in response to the deprived eye. The locus encompasses 13 genes, two of which--Stch and Nrip1--contain missense polymorphisms. The expression levels of Stch and to a lesser extent Nrip1 in whole brain correlate with the trait identifying them as novel candidate plasticity genes.     

An incremental Hebbian learning model of the primary visual cortex with lateral plasticity and real input patterns

We present a simplified binocular neural network model of the primary visual cortex with separate ON/OFF-pathways and modifiable afferent as well as intracortical synaptic couplings. Random as well as natural image stimuli drive the weight adaptation which follows Hebbian learning rules stabilized with constant norm and constant sum constraints. The simulations consider the development of orientation and ocular dominance maps under different conditions concerning stimulus patterns and lateral couplings. With random input patterns realistic orientation maps with +/- 1/2-vortices mostly develop and plastic lateral couplings self-organize into mexican hat type structures on average. Using natural greyscale images as input patterns, realistic orientation maps develop as well and the lateral coupling profiles of the cortical neurons represent the two point correlations of the input image used.     

Cortisol reduces plasticity in the kitten visual cortex.

We investigated the effect of elevated levels of cortisol on plasticity in the visual cortex of the cat. Animals were given daily injections of cortisol i.m. for 20 days starting around 35 days of age. After 10 days they were monocularly deprived, and after an additional 10 days recordings were made from the visual cortex to construct an ocular dominance histogram. The results were compared with those from normal animals of the same age, and with animals monocularly deprived for the same period but not treated with cortisol. Cortisol reduced the ocular dominance shift in a dose-dependent manner, but did not totally abolish it even at the highest doses used. Two other series of animals were recorded, one slightly later in the critical period and one slightly earlier, with care taken to give cortisol before the animals were exposed to light in the morning. In both cases, cortisol reduced the ocular dominance shift but did not abolish it. To interpret these results, we measured levels of plasma cortisol in normal cats of various ages. Average levels were fairly constant between birth and 12 months of age (0.5-1 microgram/dl), and increased slightly after that, but there was a large variation between animals. Thus elevated levels of cortisol can have a substantial effect on plasticity in the visual cortex of the cat, but the decline of the critical period for plasticity between 6 weeks and 3-5 months of age does not seem to be due to a rise in cortisol levels during this time.     

Molecular mechanisms of experience-dependent plasticity in visual cortex

A remarkable amount of our current knowledge of mechanisms underlying experience-dependent plasticity during cortical development comes from study of the mammalian visual cortex. Recent advances in high-resolution cellular imaging, combined with genetic manipulations in mice, novel fluorescent recombinant probes, and large-scale screens of gene expression, have revealed multiple molecular mechanisms that underlie structural and functional plasticity in visual cortex. We situate these mechanisms in the context of a new conceptual framework of feed-forward and feedback regulation for understanding how neurons of the visual cortex reorganize their connections in response to changes in sensory inputs. Such conceptual advances have important implications for understanding not only normal development but also pathological conditions that afflict the central nervous system.     

A precritical period for plasticity in visual cortex

One of the seminal discoveries in developmental neuroscience is that altering visual experience through monocular deprivation can alter both the physiological and the anatomical representation of the two eyes, called ocular dominance columns, in primary visual cortex. This rearrangement is restricted to a critical period that starts a few days or weeks after vision is established and ends before adulthood. In contrast to the original hypothesis proposed by Hubel and Wiesel, ocular dominance columns are already substantially formed before the onset of the critical period. Indeed, before the critical period there is a period of ocular dominance column formation during which there is robust spontaneous activity and visual experience. Recent findings raise important questions about whether activity guides ocular dominance column formation in this 'precritical period'. One developmental event that marks the passage from the precritical period to the critical period is the activation of a GABAergic circuit. How these events trigger the transition from the precritical to critical period is not known.     

Pre-attentive segmentation in the primary visual cortex

The activities of neurons in primary visual cortex have been shown to be significantly influenced by stimuli outside their classical receptive fields. We propose that these contextual influences serve pre-attentive visual segmentation by causing relatively higher neural responses to important or conspicuous image locations, making them more salient for perceptual pop-out. These locations include boundaries between regions, smooth contours, and pop-out targets against backgrounds. The mark of these locations is the breakdown of spatial homogeneity in the input. for instance, at the border between two texture regions of equal mean luminance. This breakdown causes changes in contextual influences, often resulting in higher responses at the border than at surrounding locations. This proposal is implemented in a biologically based model of VI in which contextual influences are mediated by intra-cortical horizontal connections. The behavior of the model is demonstrated using examples of texture segmentation, figure-ground segregation, target-distractor asymmetry, and contour enhancement, and is compared with psychophysical and physiological data. The model predicts (1) how neural responses should be tuned to the orientation of nearby texture borders, (2) a set of qualitative constraints on the structure of the intracortical connections, and (3) stimulus-dependent biases in estimating the locations of the region borders by pre-attentive vision.     

Adaptation-induced plasticity of orientation tuning in adult visual cortex

A key emergent property of the primary visual cortex (V1) is the orientation selectivity of its neurons. The extent to which adult visual cortical neurons can exhibit changes in orientation selectivity is unknown. Here we use single-unit recording and intrinsic signal imaging in V1 of adult cats to demonstrate systematic repulsive shifts in orientation preference following short-term exposure (adaptation) to one stimulus orientation. In contrast to the common view of adaptation as a passive process by which responses around the adapting orientation are reduced, we show that changes in orientation tuning also occur due to response increases at orientations away from the adapting stimulus. Adaptation-induced orientation plasticity is thus an active time-dependent process that involves network interactions and includes both response depression and enhancement.     

The synaptic proteome during development and plasticity of the mouse visual cortex

During brain development, the neocortex shows periods of enhanced plasticity, which enables the acquisition of knowledge and skills that we use and build on in adult life. Key to persistent modifications of neuronal connectivity and plasticity of the neocortex are molecular changes occurring at the synapse. Here we used isobaric tag for relative and absolute quantification to measure levels of 467 synaptic proteins in a well-established model of plasticity in the mouse visual cortex and the regulation of its critical period. We found that inducing visual cortex plasticity by monocular deprivation during the critical period increased levels of kinases and proteins regulating the actin-cytoskeleton and endocytosis. Upon closure of the critical period with age, proteins associated with transmitter vesicle release and the tubulin- and septin-cytoskeletons increased, whereas actin-regulators decreased in line with augmented synapse stability and efficacy. Maintaining the visual cortex in a plastic state by dark rearing mice into adulthood only partially prevented these changes and increased levels of G-proteins and protein kinase A subunits. This suggests that in contrast to the general belief, dark rearing does not simply delay cortical development but may activate signaling pathways that specifically maintain or increase the plasticity potential of the visual cortex. Altogether, this study identified many novel candidate plasticity proteins and signaling pathways that mediate synaptic plasticity during critical developmental periods or restrict it in adulthood.     

Oxygenation of the cat primary visual cortex.

Tissue PO2 was measured in the primary visual cortex of anesthetized, artificially ventilated normovolemic cats to examine tissue oxygenation with respect to depth. The method utilized 1) a chamber designed to maintain cerebrospinal fluid pressure and prevent ambient PO2 from influencing the brain, 2) a microelectrode capable of recording electrical activity as well as local PO2, and 3) recordings primarily during electrode withdrawal from the cortex rather than during penetrations. Local peaks in the PO2 profiles were consistent with the presence of numerous vessels. Excluding the superficial 200 microm of the cortex, in which the ambient PO2 may have influenced tissue PO2, there was a slight decrease (4.9 Torr/mm cortex) in PO2 as a function of depth. After all depths and cats were weighted equally, the average PO2 in six cats was 12.8 Torr, with approximately one-half of the values being 相似文献   

The symplectic structure of the primary visual cortex

We propose to model the functional architecture of the primary visual cortex V1 as a principal fiber bundle where the two-dimensional retinal plane is the base manifold and the secondary variables of orientation and scale constitute the vertical fibers over each point as a rotation–dilation group. The total space is endowed with a natural symplectic structure neurally implemented by long range horizontal connections. The model shows what could be the deep structure for both boundary and figure completion and for morphological structures, such as the medial axis of a shape.