Neural Plasticity In Visual Cortex Research Paper

In early postnatal development, both thalamocortical and corticocortical connections are known to be especially malleable by visual experience during a phase called the critical or sensitive period. In the adult, experience-dependent plasticity of thalamocortical connections seems to be very limited. However, some plasticity of corticocortical and in particular long-range intra-areal connections persists ranging from synaptic gain changes to even axonal outgrowth.

Furthermore, there is accumulating evidence that certain neuronal response properties are dynamic rather than fixed entities since they can change within minutes to hours even in the adult brain. Therefore, the transition between the visual perception process, short-term adaptation to visual context, learning and long-term adaptive changes might be continuous.

In this research paper, mainly experimental evidence of plasticity in primary visual cortex of cats or monkeys during development and in the adult will be reviewed. Links to the human will be suggested.

2. Neural Plasticity In The Visual Cortex During Development

After birth, the visual cortex of most mammals is still in a period of growth and change. The majority of neuronal response properties and connections develop only postnatally and maturation in the visual cortex seems to proceed in two distinct steps (Fregnac and Imbert 1984, Singer 1995, Schmidt et al. 1999). In the first phase, mechanisms inherent to the cortex establish a crude framework of interconnected neural modules which exhibit the basic but still immature traits of the adult state. Relevant mechanisms in this phase are assumed to consist of molecular cues and patterns of spontaneous neural activity in cortical and corticothalamic circuits. Experience-independent development is prolonged beyond eye opening in most species. It might serve to prevent substantial activity dependent remodeling before the sensory periphery and the motor control of the eyes have matured sufficiently. In a second phase, the sensitive period, the primordial layout becomes refined under the control of visual experience establishing a fine-tuned network of connections and mature response properties. Neuronal connections and cortical response properties are especially susceptible to visual experience during the latter phase. One of the main functions attributed to the sensitive period is to consolidate already established connections and to specify still-proliferating connections according to functional criteria. This process might serve to adapt the developing organism ideally to the requirements of the outside world (Singer 1995, Schmidt et al. 1999).

However, the individual outcome is not always favorable. Very early, clinical observations indicated that the ability to see in the adult might be irreversibly impaired if the unrestricted use of vision during early childhood is not assured (von Senden 1932). Congenital or early childhood cataract, corneal blurring after eye infections, and large uncorrected refractive errors prevent the development of normal vision of the affected eye when the problem is not treated within the first years of life. Misalignment of the two eyes by either strabismus or anisometropia, a refraction asymmetry between the eyes, can lead to permanent suppression of one eye resulting in poor vision (amblyopia), although the optical apparatus is intact (Duke-Elder and Wybar 1973, von Noorden 1990). Milder consequences of these disturbances are a lack of binocular functions such as stereo vision. Structural alterations reflecting observations in the human were studied in animal experiments in monkeys and cats pioneered by Hubel and Wiesel (1963).

2.1 Animal Models: Plasticity Of Thalamocortical And Intracortical Connections During Development

Thalamocortical connections and especially their specific alignment onto cortical neurons determine the selectivity of neuronal responses regarding ocularity and, partly, stimulus orientation.

The segregation of eye-specific thalamocortical afferents into ocular dominance columns seems to reach a limited level without vision. Similarly, neuronal responses to oriented contours and the organization of orientation-selective neurons into modular cortical maps improve independently of visual experience in the first phase of development (Fregnac and Imbert 1984, Schmidt et al. 1999). Besides thalamocortical connections, intracortical circuits and especially longrange intra-areal connections, which run horizontally through the cortex, influence neuronal response properties. In the adult, their terminal arbors typically cluster at regularly spaced intervals to reciprocally interconnect modules of neurons with similar response selectivity for orientation. During development, these connections also pass a first experience-independent phase in which they increase in length and gradually gain a crudely clustered termination pattern from an initially exuberant distribution (for references, see Schmidt et al. 1999). These initial events in the development of modular cortical structures and the initial emergence of neuronal response properties can only be blocked by silencing cortical activity and are therefore mainly dependent on molecular cues and patterns of spontaneous activity within the cortex.

However, in the second sensitive phase of development, already established response properties can even deteriorate markedly (for reviews, see Sherman and Spear 1982, Fregnac and Imbert 1984, Henry et al. 1994, Schmidt et al. 1999) if unimpaired binocular pattern vision is not assured. Likewise, long-range horizontal intra-areal connections do not elongate further and refine into their specific adult pattern if animals are deprived of vision until they are adult.

This is strong support for the hypothesis that during the sensitive period, visual experience guides the continuing reorganization process and that developmental plasticity is needed to integrate newly formed connections into an already existing but still growing network according to functional criteria. A couple of paradigms illustrating the strong influence of pathological visual experience on cortical structures shall be mentioned.

If one eye is deprived from contour vision during the sensitive period, most of the neurons which would normally respond equally to stimulation of both eyes will be driven almost exclusively by the non-deprived eye (Wiesel and Hubel 1963; for a review, see Sherman and Spear 1982). The functional shift starts shortly after deprivation and subsequently is followed by a removal of the synaptic terminals and terminal arbors of the deprived eye (for a review, see Schmidt et al. 1999). Ocular dominance columns formed by eyespecific afferents will shrink and thalamic relay cells will decrease in size when driven by the deprived eye (Sherman and Spear 1982). These alterations are fully reversible during the sensitive period but no longer in adulthood. Since they allow only very limited visual function of the affected eye, the importance of early interference with inborn eye diseases like ptosis, a weakness of the upper lid occluding the pupil, or cataract (opacity of the lens), becomes obvious.

Another important paradigm demonstrating the influence of visual input on both thalamocortical and intra-areal connections is strabismus. Since the optical axes of the two eyes are not aligned, activity delivered from normally corresponding retinal loci to the cortex is uncorrelated. As a consequence, all cortical neurons become almost exclusively responsive to stimulation of only one eye, and thalamocortical afferents of the two eyes are completely non-overlapping (for a review, see Stryker 1991). Furthermore, long-range intra-areal connections, which normally are not eye-specific, come to connect only cortical neurons driven by the same eye (for a review, see Singer 1995). It is likely that binocular fusion and therefore stereo vision in strabismics are disturbed because parts of the visual system, thalamocortical, and intra-areal circuits are completely separated by eye.

An example, particularly emphasizing the instructive role of vision, is selective rearing in an environment displaying contours of only one orientation which will enhance the number of neurons in the adult responding to that particular stimulus orientation (Henry et al. 1994).

2.2 Mechanisms Of Developmental Plasticity

Useor experience-dependent changes of connectivity during development can be interpreted to follow Hebbian (1949) modification rules (Rauschecker and Singer 1981, Stryker 1991, Singer 1995). According to Hebb’s idea, which was modified by Stent (1973) for activity-dependent synaptic plasticity, the synaptic coupling of an afferent fiber and a postsynaptic target neuron is strengthened when they are activated at the same time. Synaptic connections to cells which fire uncorrelated or are inactive are destabilized. The deprivation and strabismus-induced alterations in ocular dominance development can be therefore seen as the result of an activity-dependent competition between the eye-specific afferents for postsynaptic neurons in the cortex. Cortical target neurons seem to strengthen their connection to only the sort of afferents providing the input which matches other local activity patterns. Postsynaptic activation is presumably required for changes to occur (Rauschecker and Singer 1981). Metabolically, changes involve glutamatergic synaptic transmission via NMDA receptors, are gated by neuromodulators such as norepinephrine, acetylcholine and serotonin, and are also dependent on local concentrations of neurotrophic substances (Berardi et al. 2000).

3. Neural Plasticity Of Visual Cortex In The Adult

There is also evidence for plasticity of cortical functional properties and connections in the adult brain. It is well established that representations in the primary visual cortex can be reorganized reversibly as well as permanently following visual conditioning, restricted deafferentiation, or electrical stimulation.

3.1 Retinal Lesions

Visual cortical map reorganization was first demonstrated after retinal lesions in both monkey and cat primary visual cortex. When cortical neurons are deprived of all their normal input by binocular lesions affecting corresponding retinal loci, they acquire new or modified receptive fields driven by inputs from intact retinal regions surrounding the lesions (Kaas 1991, Buonomano and Merzenich 1998, Gilbert 1998).

In the primary visual cortex of cats, substantial reorganization on a small spatial scale occurs within hours, similar to observations in the somatosensory system (Buonomano and Merzenich 1998). After recovery periods of more than 2–3 months, the majority of the neurons which lost their visual input start to respond to parts of the visual field to which they did not respond before. Finally, orientation and direction selectivity can recover to normal levels but responsiveness might remain reduced and receptive field borders less defined (for a review, see Gilbert 1998).

Obviously, cortical rearrangements caused by retinal lesions could serve to mask the actual loss of visual input and to create a continuous visual perception. This is observed mainly with lesions in the peripheral visual field, e.g., with postinfectional retinal scars or after preventive retinal laser coagulation in certain eye diseases (diabetes, myopia).

3.2 Visual Conditioning

As also observed in monkey and human somatosensory and motor cortex, representational plasticity in the visual system can occur without lesioning the sensory periphery (retina). After several months, neurons of adult monkeys fitted with prisms that reverse the visual field developed new receptive fields in the ipsilateral hemifield that normally only activates neurons in the contralateral cortex. Obviously, lasting changes in the visual input—not necessarily lesions— are sufficient to induce rearrangements in cortical representations. Context-dependent dynamic alterations of neuronal responsiveness and receptive field size occur also on a very short time scale. When stimulated with an artificial scotoma, a gray occluder covering receptive fields of the recorded neurons surrounded by a texture or dynamic noise, neurons with receptive fields inside the scotoma start to respond as if there were no occluder at all after a few seconds or even increase their receptive field such that they can be excited by surrounding stimuli after minutes (Gilbert 1998). Such short-term changes certainly operate within a transitional zone between mere adaptation and short-term plasticity, since they are fully reversible within seconds. They are thought to correspond to the psychophysical phenomenon of filling-in which is the basis for perceiving continuous images despite physiological disruptions like, for example, the blind spot (Ramachandran 1993).

3.3 Neuronal Substrate Of Adult Cortical Plasticity

For several reasons, the observed long-and short-term modifications in the adult visual cortex are thought to be mainly mediated by long-range intra-areal connections. First, their large horizontal extent and characteristic functional selectivity makes them ideally suited to transmit feature-specific information over a large region of visual space and thus act within visual context. Second, after retinal lesions, reorganized receptive fields match the former response properties to oriented contours of that cortical region. However, thalamocortical connections do not sprout into the silenced cortical area. Therefore, the orientation-specific information can only be conveyed by intracortical orientation-specific connections. Third, collaterals of intracortical connections have indeed been demonstrated to branch and give rise to new synaptic boutons within the cortical region representing the scotoma (Gilbert 1998).

3.4 Mechanisms Of Adult Plasticity

Short-term modifications such as enhanced neuronal responsiveness and receptive field expansion are thought to be mainly achieved by rapid modulations of the efficacy of preexisting connections enabling subthreshold excitatory inputs to effectively drive cortical neurons by either suppressing inhibitory or potentiating excitatory connections (Gilbert 1998).

After retinal lesions, a cascade of metabolic changes seem to precede long-term reorganization (for a review, see Eysel et al. 1999). In the weeks following the immediate expansion of receptive fields, decreased GABA-mediated inhibition within and a shift of hyperexcitability from its border towards the silenced site are observed until normal activity relations are restored. These changes are accompanied by increased spontaneous and visually driven activity and enhanced ability to induce long-term potentiation (LTP). Mechanisms using LTP could lead to long-lasting changes in the efficacy of existing synapses of long-range horizontal connections and the additional secretion of neurotrophic substances might finalize the local cortical reorganization through formation of new synapses and sprouting of axon collaterals.

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