GABAA receptor diversity and pharmacology

Because of its control of spike-timing and oscillatory network activity, gamma-aminobutyric acid (GABA)-ergic inhibition is a key element in the central regulation of somatic and mental functions. The recognition of GABA(A) receptor diversity has provided molecular tags for the analysis of distinct neuronal networks in the control of specific pharmacological and physiological brain functions. Neurons expressing alpha(1)GABA(A) receptors have been found to mediate sedation, whereas those expressing alpha(2)GABA(A) receptors mediate anxiolysis. Furthermore, associative temporal and spatial memory can be regulated by modulating the activity of hippocampal pyramidal cells via extrasynaptic alpha(5)GABA(A) receptors. In addition, neurons expressing alpha(3)GABA(A) receptors are instrumental in the processing of sensory motor information related to a schizophrenia endophenotype. Finally, during the postnatal development of the brain, the maturation of GABAergic interneurons seems to provide the trigger for the experience-dependent plasticity of neurons in the visual cortex, with alpha(1)GABA(A) receptors setting the time of onset of a critical period of plasticity. Thus, particular neuronal networks defined by respective GABA(A) receptor subtypes can now be linked to the regulation of various clearly defined behavioural patterns. These achievements are of obvious relevance for the pharmacotherapy of certain brain disorders, in particular sleep dysfunctions, anxiety disorders, schizophrenia and diseases associated with memory deficits.