Abstract
Brain function depends on co-ordinated transmission of signals from both excitatory and inhibitory neurotransmitters acting upon target neurons. NMDA, AMPA and mGluR receptors are the major subclasses of glutamate receptors that are involved in excitatory transmission at synapses, mechanisms of activity dependent synaptic plasticity, brain development and many neurological diseases. In addition to canonical role of regulating presynaptic release and activating postsynaptic potassium channels, GABAB receptors also regulate glutamate receptors. There is increasing evidence that metabotropic GABAB receptors are now known to play an important role in modulating the excitability of circuits throughout the brain by directly influencing different types of postsynaptic glutamate receptors. Specifically, GABAB receptors affect the expression, activity and signaling of glutamate receptors under physiological and pathological conditions. Conversely, NMDA receptor activity differentially regulates GABAB receptor subunit expression, signaling and function. In this review I will describe how GABAB receptor activity influence glutamate receptor function and vice versa. Such a modulation has widespread implications for the control of neurotransmission, calcium-dependent neuronal function, pain pathways and in various psychiatric and neurodegenerative diseases.
Highlights
Sriharsha Kantamneni *Bradford School of Pharmacy, School of Life Sciences, University of Bradford, Bradford, West Yorkshire, UK
Most excitatory signals that a neuron receives are mediated via glutamate receptors whereas most inhibitory signals are mediated via γ-aminobutyric acid (GABA) receptors (Cherubini et al, 1991; Hollmann and Heinemann, 1994)
Pharmacological and molecular biological studies have revealed that glutamate receptors exist as different subclasses, where receptor subtypes comprise multiple subunits such as NMDA receptors (GluN1 to GluN3), AMPA receptors (GluA1 to GluA4), kainate receptors (GluK1 to GluK5) and mGlu receptors
Summary
Bradford School of Pharmacy, School of Life Sciences, University of Bradford, Bradford, West Yorkshire, UK. NMDA, AMPA and mGluR receptors are the major subclasses of glutamate receptors that are involved in excitatory transmission at synapses, mechanisms of activity dependent synaptic plasticity, brain development and many neurological diseases. There is increasing evidence that metabotropic GABAB receptors are known to play an important role in modulating the excitability of circuits throughout the brain by directly influencing different types of postsynaptic glutamate receptors. NMDA receptor activity differentially regulates GABAB receptor subunit expression, signaling and function. In this review I will describe how GABAB receptor activity influence glutamate receptor function and vice versa. Such a modulation has widespread implications for the control of neurotransmission, calcium-dependent neuronal function, pain pathways and in various psychiatric and neurodegenerative diseases
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