GABAB receptors: modulation of thalamocortical dynamics and synaptic plasticity

Abstract

GABA_B-receptors (GABA_B-Rs) are metabotropic, G protein-coupled receptors for the neurotransmitter GABA. Their activation induces slow inhibitory control of the neuronal excitability mediated by pre- and postsynaptic inhibition. Presynaptically GABA_B-Rs reduce GABA and glutamate release inhibiting presynaptic Ca²⁺ channels in both inhibitory and excitatory synapses while postsynaptic GABA_B-Rs induce robust slow hyperpolarization by the activation of K⁺ channels. GABA_B-Rs are activated by non-synaptic or volume transmission, which requires high levels of GABA release, either by the simultaneous discharge of GABAergic interneurons or very intense discharges in the thalamus or by means of the activation of a neurogliaform interneurons in the cortex. The main receptor subunits GABA_B1a, GABA_B1b and GABA_B2 are strongly expressed in neurons and glial cells throughout the central nervous system and GABA_B-R activation is related to many neuronal processes such as the modulation of rhythmic activity in several brain regions. In the thalamus, GABA_B-Rs modulate the generation of the main thalamic rhythm, spindle waves. In the cerebral cortex, GABA_B-Rs also modulate the most prominent emergent oscillatory activity-slow oscillations-as well as faster oscillations like gamma frequency. Further, recent studies evaluating the complexity expressed by the cortical network, a parameter associated with consciousness levels, have found that GABA_B-Rs enhance this complexity, while their blockade decreases it. This review summarizes the current results on how the activation of GABA_B-Rs affects the interchange of information between brain areas by controlling rhythmicity as well as synaptic plasticity.

Keywords: GABA(B)-Rs; Up states; cortical complexity; metabotropic; perigeniculate; reticularis; slow oscillations.