Functional consequences of the disturbances in the GABA-mediated inhibition induced by injuries in the cerebral cortex

Abstract

Cortical injuries are often reported to induce a suppression of the intracortical GABAergic inhibition in the surviving, neighbouring neuronal networks. Since GABAergic transmission provides the main source of inhibition in the mammalian brain, this condition may lead to hyperexcitability and epileptiform activity of cortical networks. However, inhibition plays also a crucial role in limiting the plastic properties of neuronal circuits, and as a consequence, interventions aiming to reestablish a normal level of inhibition might constrain the plastic capacity of the cortical tissue. A promising strategy to minimize the deleterious consequences of a modified inhibitory transmission without preventing the potential beneficial effects on cortical plasticity may be to unravel distinct GABAergic signaling pathways separately mediating these positive and negative events. Here, gathering data from several recent studies, we provide new insights to better face with this "double coin" condition in the attempt to optimize the functional recovery of patients.

Figure 1

Schematic illustration representing a model pyramidal neuron in the cortex surrounding the lesion with its excitatory and inhibitory inputs before, shortly after and some weeks after the lesion occurrence. This model shows the potential cellular mechanisms responsible for the functional rewiring of neuronal networks following cortical injuries. (a) Before the occurrence of a cortical lesion, some excitatory inputs are subthreshold (arrow) being masked by strong inhibitory inputs; (b) early after the cortical lesion occurrence (first week postlesion), subthreshold connections can be converted into functional (suprathreshold) ones (arrow) by the lesion-induced weakening of inhibitory inputs; (c) some weeks after the lesion, experience-dependent plastic processes will likely lead to the reinforcement of some of the new functional inputs, which turn out to be behavioral relevant after the lesion (black arrow) and to the suppression of excitatory inputs which became irrelevant (blue arrow). For clarity, many cellular and subcellular elements have been omitted; this draw represents, therefore, an oversimplification of a real scenario.