GABAergic Circuit Development and Its Implication for CNS Disorders

The function of the cerebral cortex requires the coordinated action of two major neuronal subtypes, the glutamatergic projection neurons and the GABAergic interneurons. Although, in terms of numbers, GABAergic interneurons represent a minor cell population compared to glutamatergic neurons in the neocortex, they play an important role in modulating network dynamics of neocortical circuits. Indeed, GABAergic interneurons have been shown to control neuronal excitability and integration, and they have been implicated in the generation of temporal synchrony and oscillatory behavior among networks of pyramidal neurons. Such oscillations within and across neural systems are believed to serve various complex functions, such as perception, movement initiation, and memory. Recently, the development of GABAergic inhibition has been shown to be a key determinant for critical period plasticity of cortical circuits. Critical periods represent heightened epochs of brain plasticity, during which experience can produce permanent, large-scale changes in neuronal circuits. Experience-dependent refinement of neural circuits has been described in many regions within the CNS, suggesting it is a fundamental mechanism for normal vertebrate CNS development. By regulating the onset and closure of critical periods, GABAergic interneurons may influence how experience shapes brain wiring during early life and adolescence