Abstract
Inhibitory synapses represent a minority of the total chemical synapses in the mammalian brain, yet proper tuning of inhibition is fundamental to shape neuronal network properties. The neurotransmitter γ-aminobutyric acid (GABA) mediates rapid synaptic inhibition by the activation of the type A GABA receptor (GABAAR), a pentameric chloride channel that governs major inhibitory neuronal transduction in the nervous system. Impaired GABA transmission leads to a variety of neuropsychiatric diseases, including schizophrenia, autism, epilepsy or anxiety. From an evolutionary perspective, GABAAR shows remarkable conservations, and are found in all eukaryotic clades and even in bacteria and archaea. Specifically, bona fide GABAARs are found in the nematode Caenorhabditis elegans. Because of the anatomical simplicity of the nervous system and its amenability to genetic manipulations, C. elegans provide a powerful system to investigate the molecular and cellular biology of GABA synapses. In this mini review article, we will introduce the structure of the C. elegans GABAergic system and describe recent advances that have identified novel proteins controlling the localization of GABAARs at synapses. In particular, Ce-Punctin/MADD-4 is an evolutionarily-conserved extracellular matrix protein that behaves as an anterograde synaptic organizer to instruct the excitatory or inhibitory identity of postsynaptic domains.
Highlights
Neurochemical synapses are the elementary structures that process the directional transfer of electrical signals in neural circuits
The postsynaptic assembly of cholinergic and GABAergic neuromuscular junctions (NMJs) in C. elegans relies on a recently-identified anterograde synaptic organizer Ce-Punctin/MADD-4 (Muscle Arm Development Defective-4)
Disruption of nlg-1 causes a redistribution of the GABAARs out of the GABA receptor domains and a reduction of the frequency and amplitude of spontaneous miniature inhibitory postsynaptic currents
Summary
Neurochemical synapses are the elementary structures that process the directional transfer of electrical signals in neural circuits. Based on functional (Liu et al, 2007) and EM data (White et al, 1986), each synaptic bouton likely activates receptors present on more than one postsynaptic muscle arm facing the presynaptic active zone. Because of the relatively sparse distribution of presynaptic boutons and their highly reproducible patterns across animals, forward genetic screens were successful in identifying mutants with abnormal synapses using fluorescentlytagged presynaptic proteins expressed in GABA motoneurons.
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