A switch from inter-ocular to inter-hemispheric suppression following monocular deprivation in the rat visual cortex.

Binocularity is a key property of primary visual cortex (V1) neurons that is widely used to study synaptic integration in the brain and plastic mechanisms following an altered visual experience. However, it is not clear how the inputs from the two eyes converge onto binocular neurons, and how their interaction is modified by an unbalanced visual drive. Here, using visual evoked potentials recorded in the juvenile rat V1, we report evidence for a suppressive mechanism by which contralateral eye activity inhibits responses from the ipsilateral eye. Accordingly, we found a lack of additivity of the responses evoked independently by the two eyes in the V1, and acute silencing of the contralateral eye resulted in the enhancement of ipsilateral eye responses in cortical neurons. We reverted the relative cortical strength of the two eyes by suturing the contralateral eye shut [monocular deprivation (MD)]. After 7 days of MD, there was a loss of interocular suppression mediated by the contralateral, deprived eye, and weak inputs from the closed eye were functionally inhibited by interhemispheric callosal pathways. We conclude that interocular suppressive mechanisms play a crucial role in shaping normal binocularity in visual cortical neurons, and a switch from interocular to interhemispheric suppression represents a key step in the ocular dominance changes induced by MD. These data have important implications for a deeper understanding of the key mechanisms that underlie activity-dependent rearrangements of cortical circuits following alteration of sensory experience.

Visual callosal connections: role in visual processing in health and disease.

Visual cortical areas in the two sides of the brain are interconnected by interhemispheric fibers passing through the splenium of the corpus callosum. In this review, we summarize data concerning the anatomical features of visual callosal connections, their roles in basic visual processing, and how their alterations contribute to visual deficits in different human neuropathologies. Splenial fibers represent a population of excitatory axons with varying diameters, which interconnect cortical columns with similar functional properties (i.e., same orientation selectivity) in the two hemispheres. Their branches activate simultaneously distinct iso-oriented columns in the contralateral hemisphere, thus mediating forms of stimulus-dependent interhemispheric synchronization. Callosal branches also make synapses onto GABAergic cells, resulting in an inhibitory modulation of visual processing that involves both iso-oriented and cross-oriented cortical networks. Interhemispheric inhibition appears to predominate at short latencies following callosal activation, whereas excitation becomes more robust with increasing delays. These callosal effects are dynamically adapted to the incoming visual activity, so that stimuli providing only weak afferent input are facilitated by callosal pathways, whereas strong visual input via the retinogeniculate pathway tends to be offset by transcallosal inhibition. We also review data highlighting the contribution of callosal input activity to maturation of visual function during early 'critical periods' in brain development and describe how interhemispheric transfer of visual information is rerouted in cases of callosal agenesis or following splenial damage. Finally, we provide an overview of alterations in splenium anatomy or function that may be at the basis of visual defects in several pathologic conditions.

Structural underpinnings of functional plasticity in rodent visual cortex.

Functional plasticity in rodent visual cortex has been intensively studied since the pioneering experiments of Hubel and Wiesel in the sixties. Nevertheless, the structural modifications underlying this phenomenon remain elusive. In this article, we will review recent data focused on the dynamic of excitatory and inhibitory synapses and their structural changes linked to functional modifications. We also review novel evidence on structural remodeling that promote functional plasticity and on the role of cytoskeleton modifications in experience-dependent plasticity of rodent visual cortex.

Tetanus neurotoxin-induced epilepsy in mouse visual cortex.

Tetanus neurotoxin (TeNT) is a metalloprotease that cleaves the synaptic protein VAMP/synaptobrevin, leading to focal epilepsy. Although this model is widely used in rats, the time course and spatial specificity of TeNT proteolytic action have not been precisely defined. Here we have studied the biochemical, electrographic, and anatomic characteristics of TeNT-induced epilepsy in mouse visual cortex (V1). We found that VAMP cleavage peaked at 10 days, was reduced at 21 days, and completely extinguished 45 days following TeNT delivery. VAMP proteolysis was restricted to the injected V1 and ipsilateral thalamus, whereas it was undetectable in other cortical areas. Electrographic epileptiform activity was evident both during and after the time window of TeNT effects, indicating development of chronic epilepsy. Anatomic analyses found no evidence for long-term tissue damage, such as neuronal loss or microglia activation. These data show that TeNT reliably induces nonlesional epilepsy in mouse cortex. Due to the excellent physiologic knowledge of the visual cortex and the availability of mouse transgenic strains, this model will be useful for examining the network and cellular alterations underlying hyperexcitability within an epileptic focus.

The corpus callosum and the visual cortex: plasticity is a game for two.

Throughout life, experience shapes and selects the most appropriate brain functional connectivity to adapt to a changing environment. An ideal system to study experience-dependent plasticity is the visual cortex, because visual experience can be easily manipulated. In this paper, we focus on the role of interhemispheric, transcallosal projections in experience-dependent plasticity of the visual cortex. We review data showing that deprivation of sensory experience can modify the morphology of callosal fibres, thus altering the communication between the two hemispheres. More importantly, manipulation of callosal input activity during an early critical period alters developmental maturation of functional properties in visual cortex and modifies its ability to remodel in response to experience. We also discuss recent data in rat visual cortex, demonstrating that the corpus callosum plays a role in binocularity of cortical neurons and is involved in the plastic shift of eye preference that follows a period of monocular eyelid suture (monocular deprivation) in early age. Thus, experience can modify the fine connectivity of the corpus callosum, and callosal connections represent a major pathway through which experience can mediate functional maturation and plastic rearrangements in the visual cortex.

Neurons Generated by Mouse ESCs with Hippocampal or Cortical Identity Display Distinct Projection Patterns When Co-transplanted in the Adult Brain.

The capability of generating neural precursor cells with distinct types of regional identity in vitro has recently opened new opportunities for cell replacement in animal models of neurodegenerative diseases. By manipulating Wnt and BMP signaling, we steered the differentiation of mouse embryonic stem cells (ESCs) toward isocortical or hippocampal molecular identity. These two types of cells showed different degrees of axonal outgrowth and targeted different regions when co-transplanted in healthy or lesioned isocortex or in hippocampus. In hippocampus, only precursor cells with hippocampal molecular identity were able to extend projections, contacting CA3. Conversely, isocortical-like cells were capable of extending long-range axonal projections only when transplanted in motor cortex, sending fibers toward both intra- and extra-cortical targets. Ischemic damage induced by photothrombosis greatly enhanced the capability of isocortical-like cells to extend far-reaching projections. Our results indicate that neural precursors generated by ESCs carry intrinsic signals specifying axonal extension in different environments.

Altered sensory processing and dendritic remodeling in hyperexcitable visual cortical networks.

Epilepsy is characterized by impaired circuit function and a propensity for spontaneous seizures, but how plastic rearrangements within the epileptic focus trigger cortical dysfunction and hyperexcitability is only partly understood. Here we have examined alterations in sensory processing and the underlying biochemical and neuroanatomical changes in tetanus neurotoxin (TeNT)-induced focal epilepsy in mouse visual cortex. We documented persistent epileptiform electrographic discharges and upregulation of GABAergic markers at the completion of TeNT effects. We also found a significant remodeling of the dendritic arbors of pyramidal neurons, with increased dendritic length and branching, and overall reduction in spine density but significant preservation of mushroom, mature spines. Functionally, spontaneous neuronal discharge was increased, visual responses were less reliable, and electrophysiological and behavioural visual acuity was consistently impaired in TeNT-injected mice. These data demonstrate robust, long-term remodeling of both inhibitory and excitatory circuitry associated with specific disturbances of network function in neocortical epilepsy.

Functional masking of deprived eye responses by callosal input during ocular dominance plasticity.

Monocular deprivation (MD) is a well-known paradigm of experience-dependent plasticity in which cortical neurons exhibit a shift of ocular dominance (OD) toward the open eye. The mechanisms underlying this form of plasticity are incompletely understood. Here we demonstrate the involvement of callosal connections in the synaptic modifications occurring during MD. Rats at the peak of the critical period were deprived for 7 days, resulting in the expected OD shift toward the open eye. Acute microinjection of the activity blocker muscimol into the visual cortex contralateral to the recording site restored binocularity of cortical cells. Continuous silencing of callosal input throughout the period of MD also resulted in substantial attenuation of the OD shift. Blockade of interhemispheric communication selectively enhanced deprived eye responses with no effect on open eye-driven activity. We conclude that callosal inputs play a key role in functional weakening of less active connections during OD plasticity.