R OLE OF INTERHEMISPHERIC CONNECTIONS IN VISUAL CORTEX PLASTICITY

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ABSTRACT

R OLE OF INTERHEMISPHERIC CONNECTIONS IN VISUAL CORTEX PLASTICITY

The corpus callosum is the main fibre bundle of the central nervous system and in humans is composed of almost 200 millions of axons. The aim of this thesis in an investigation of the role of interhemispheric connections in visual cortical plasticity during the critical period of post-natal development in the rat.

In the first part of the thesis we evaluated the role of the callosum in cortical binocularity. To this aim, we measured the responses evoked by each eye in the visual cortex before and after silencing activity of the contralateral hemisphere.

Rats of 24-29 days of age (P24-P29) were anesthetized with urethane and the responses driven by the two eyes were quantified by Visual Evoked Potentials (VEPs). The activity was silenced by an intracortical stereotaxic injection of the GABA

receptor agonist muscimol. The results show a significant shift in ocular dominance following blockade of interhemispheric communication. Indeed, the ratio between the responses evoked by the contralateral and ipsilateral eye significantly increases after muscimol infusion (VEP contra/ipsi ratio: before muscimol 1,59 ± 0,28 s.d.; post muscimol 2,43 ± 0,88 s.d.; paired t-test, p<0.01). Injection of saline solution as control had no effect on binocularity (paired t-test, p=0,89).

These data prompted us to investigate whether callosal connections are involved in the plastic mechanisms that lead to a shift in binocularity. To do this, we took advantage of the classical paradigm of monocular deprivation, that consists in blocking visual input through one eye by suturing the eyelids during the critical period.

A group of rats underwent monocular deprivation starting from P21-P23.

Electrophysiologial recordings made after one week showed, as expected, a shift of

ocular dominance towards the open eye. This shift is at least partially recovered by

silencing the callosal input via muscimol infusion (contra/ipsi ratio: before muscimol

0,48 ± 0,10 s.d.; post muscimol 0,91 ± 0,17 s.d.; paired t-test, p<0.001). Data

2 show that the corpus callosum exerts a selective inhibition on deprived eye inputs, with no significant effect on the open eye responses. Despite the enhancement of the response at low spatial frequency, spatial resolution of the closed eye (visual acuity) did not change following muscimol injection.

These data show that transcallosal inhibition plays an important role in the plastic

processes that follow monocular deprivation. Ongoing experiments are focused on

clarifying the mechanisms through which the callosum exerts these effects. In

particular, we didn’t find any change in the neurochemical phenotype (excitatory

vs. inhibitory) of the callosal neurons following deprivation. This result suggests

that transcallosal inhibition is mediated by the recruitment of GABAergic

interneurons in the contralateral hemisphere.