Abstract
SummaryPentameric ligand-gated ion channels (LGICs) play conserved, critical roles in both excitatory and inhibitory synaptic transmission and can be activated by diverse neurochemical ligands. We have performed a characterization of orphan channels from the nematode C. elegans, identifying five new monoamine-gated LGICs with diverse functional properties and expression postsynaptic to aminergic neurons. These include polymodal anion channels activated by both dopamine and tyramine, which may mediate inhibitory transmission by both molecules in vivo. Intriguingly, we also find that a novel serotonin-gated cation channel, LGC-50, is essential for aversive olfactory learning of pathogenic bacteria, a process known to depend on serotonergic neurotransmission. Remarkably, the redistribution of LGC-50 to neuronal processes is modulated by olfactory conditioning, and lgc-50 point mutations that cause misregulation of receptor membrane expression interfere with olfactory learning. Thus, the intracellular trafficking and localization of these receptors at synapses may represent a molecular cornerstone of the learning mechanism.
Highlights
Synaptic plasticity, the selective strengthening or weakening of individual synaptic connections, is fundamental to the diverse forms of learning and memory in all animals
Deorphanization of novel amine-gated ligand-gated ion channels (LGICs) a number of monoamine receptors have been identified in C. elegans, many neurons receiving synaptic input from aminergic neurons express no known aminergic receptor.[13]
Three C. elegans LGCs have been previously described as monoamine gated,[7,8,14] but many predicted LGICs had no characterized endogenous ligand
Summary
The selective strengthening or weakening of individual synaptic connections, is fundamental to the diverse forms of learning and memory in all animals. At the molecular and cellular levels, most forms of synaptic plasticity are thought to involve alterations in the abundance, density, or sensitivity of ionotropic neurotransmitter receptors at the postsynaptic membrane. These ionotropic receptors fall into two general types: the nicotinic acetylcholine receptors (nAChRs) from the Cys-loop family of pentameric ligand-gated ion channels (LGICs) and the tetrameric ionotropic glutamate receptors (GluRs). It is not well understood to what extent non-nAChR Cys-loop channels are important in the molecular mechanism that underpins learning and synaptic plasticity
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