The GABA System of the Mammalian CNS

Abstract

My current working models of nervous system function are based partly on many experimental observations, often supported by extensive immunocytochemical findings, and partly on their extrapolation into reasonable potentialities. Particular emphasis is placed on consideration of the roles of inhibitory GABAergic neurons in normal and abnormal information processing in the CNS. The point of view taken is that the nervous system is highly restrained, with inhibitory neurons acting like reins that serve to keep the neuronal “horses” from running away. It is proposed that in behavioral sequences, innate or learned, preprogrammed circuits are released to function at varying rates and in various combinations. This is accomplished largely by the disinhibition of pacemaker neurons whose activities are under the control of tonically active inhibitory command neurons, many of which use GABA as a transmitter. According to this view, disinhibition is permissive, and excitatory input to pacemaker neurons has mainly a modulatory role. In addition to the above restraining function, local circuit GABAergic neurons participate in processes that result in producing feedforward, feedback, surround, and presynaptic inhibition and presynaptic facilitation. Information arriving from several sources is integrated in specialized command centers such as the cerebellar cortex, the basal ganglia, and the reticular nucleus of the thalamus which, through inhibitory GABAergic neurons, exert high frequency monosynaptic tonic inhibition in various brain regions. The analysis of the inputs to the command regions is reflected, with variable time delays, in decreased frequencies of firing of appropriate combinations of their inhibitory output neurons, releasing neural activity in the direct channels to which they project, so that it becomes optimally compatible temporally and spatially with activity elsewhere in the CNS.