Guiding synaptic plasticity toward specific features of visual functions

This abstract is dedicated to the memory of Prof. Matteo Caleo

After a focal damage in the cerebral cortex, areas in the territory of the lesion undergo a sudden loss of function which impacts dramatically on the physiology of these regions. Restoring functional connections implies a fine synaptic weights modulation of the network, but currently, there are no ways to modulate connection strength among specific populations of neurons.
The aim of this work is to exploit spike-timing-dependent plasticity (STDP) rule to functionally guide the rearrangement of perilesional neural connections after a stab wound lesion in the primary visual cortex. We applied this strategy in head-fixed awake injured mice by coupling a specifically oriented visual stimulation with cortical optogenetic activation of V1. Mice were previously injected with an adeno-associated virus encoding for channelrhodopsin2 and were subjected to a pairing protocol for 2 weeks after the lesion. The protocol consisted of a daily visual stimulation of abrupt reversal square gratings, in which one hemicycle was coupled with optogenetic stimulation of cortical neurons, in phase with the physiological response of V1 neurons. During the same training session, visual stimulations for the orthogonal orientation were presented without optogenetic stimulation, as internal control.

Evaluation of visual evoked potential (VEP) amplitudes after two weeks of training revealed a significant orientation preference toward the paired orientation that is exclusive for the hemicycle that was coupled with optogenetics. Longitudinal recordings confirmed long-lasting orientation preference up to 2 weeks after the ending of the training protocol, even at the level of multi-unit activity.

In summary, this study provides a proof of principle that using STDP as a tool to guide synaptic plasticity is a potential way to restore lost function after a brain lesion.