Biology subjects

Morud, J.

Publications and source records attributed to Morud, J..

5 recordsLinked to original sources

bioRxiv2026

The copine protein NRA-1 regulates activity-dependent cholinergic signalling and sensory integration in C. elegans

Membrane-associated proteins regulate the localisation and function of ligand-gated ion channels, yet how they shape synaptic efficacy and behaviour remains poorly understood. Here, we identify the copine family protein NRA-1 as an activity-dependent regulator of cholinergic signalling and sensory circuit function. Electrophysiological recordings at the neuromuscular junction of C. elegans revealed that loss of nra-1 does not alter responses to acute agonist application or the initial response to synaptic stimulation but selectively impairs sustained and repetitive cholinergic transmission during ongoing activity. Single-channel recordings further demonstrated that NRA-1 does not affect the unitary conductance of levamisole-sensitive acetylcholine receptors (L-AChRs) but instead regulates receptor gating by increasing channel closed times and reducing opening frequency, resulting in an overall decrease in receptor activity. Despite these synaptic defects, nra-1 mutants displayed normal baseline locomotion but exhibited impaired chemotaxis, abnormal food localisation and defective egg-laying behaviour. Together, our findings identify NRA-1 as an activity-dependent regulator of postsynaptic receptor function that sustains cholinergic signalling during repeated activity and links receptor dynamics to sensory behaviour. These results establish copine proteins as important modulators of synaptic efficacy and suggest that activity-dependent control of receptor function represents a conserved mechanism for tuning neural circuit performance.

neuroscience↗

bioRxiv2025

Intracellular Regulation of a Serotonin-Gated Ion Channel Links Receptor Trafficking to Memory

Learning and memory arise from synaptic plasticity, the ability of neurons to modify connectivity through experience-dependent changes in receptor localisation and signalling. Here, we identify a short intracellular motif within the serotonin-gated ion channel LGC-50 that links molecular receptor dynamics to behavioural plasticity in Caenorhabditis elegans. Deletion of residues 363-379 in the intracellular M3-4 loop caused receptor clustering in intracellular compartments and abolished learning-induced redistribution without altering receptor function or immediate memory recall. Interestingly, animals expressing the truncated receptor failed to retrieve aversive memories one hour after training, revealing a role for receptor trafficking in memory stability. Combining molecular, ultrastructural and behavioural analyses in vivo, we show how intracellular receptor motifs govern experience-dependent plasticity. These findings demonstrate that precise receptor localisation and trafficking shape neural circuit adaptation and reveal a conserved mechanism by which receptor dynamics support the persistence and retrieval of memory across species.

neuroscience↗

bioRxiv2021

Neuronally Produced Betaine Acts via a Novel Ligand Gated Ion Channel to Control Behavioural States

Trimethyl glycine, or betaine, is an amino acid derivative found in diverse organisms, from bacteria to plants and animals. It can function as an osmolyte to protect cells against osmotic stress, and building evidence suggests betaine may also play important functional roles in the nervous system. However, despite growing interest in betaines roles in the nervous system, few molecular mechanisms have been elucidated. Here we identify the expression of betaine synthesis pathway genes in the nervous system of the nematode worm, C. elegans. We show that betaine, produced in a single pair of interneurons, the RIMs, can control complex behavioural states. Moreover, we also identify and characterise a new betaine-gated inhibitory ligand gated ion channel, LGC-41, which is required for betaine related behavioural changes. Intriguingly we observed expression of LGC-41 in punctate structures across several sensory and interneurons, including those synaptically connected to the RIMs. Our data presents a neuronal molecular mechanism for the action of betaine, via a specific receptor, in the control of complex behaviour within the nervous system of C. elegans. This may suggest a much broader role for betaine in the regulation of animal nervous systems than previously recognised.

neuroscience↗

bioRxiv2021

A Novel and Functionally Diverse Class of Acetylcholine-gated Ion Channels

Fast cholinergic neurotransmission is mediated by acetylcholine-gated ion channels; in particular, excitatory nicotinic acetylcholine receptors play well established roles in virtually all nervous systems. Acetylcholine-gated inhibitory channels have also been identified in some invertebrate phyla, yet their roles in the nervous system are less well understood. We report the existence of multiple new inhibitory acetylcholine-gated ion channels with diverse ligand binding properties in C. elegans. We identify three channels, LGC-40, LGC-57 and LGC-58, whose primary ligand is choline rather than acetylcholine, as well as the first evidence of a truly polymodal channel, LGC-39, which is activated by both cholinergic and aminergic ligands. Using our newly deorphanised channel evidence we uncover the surprising extent to which a single neuron expresses both excitatory and inhibitory channels, not only for acetylcholine but also the other major neurotransmitters. The results presented in this study offer a new insight into the potential evolutionary benefit of a vast and diverse repertoire of LGICs to generate complexity in an anatomically compact nervous system.

neuroscience↗

bioRxiv2020

Deorphanisation of novel biogenic amine-gated ion channels identifies a new serotonin receptor for learning

Pentameric ligand-gated ion channels (LGCs) play conserved, critical roles in fast synaptic transmission, and changes in LGC expression and localisation are thought to underlie many forms of learning and memory. The C. elegans genome encodes a large number of LGCs without a known ligand or function. Here, we deorphanize five members of a family of Cys-loop LGCs by characterizing their diverse functional properties that are activated by biogenic amine neurotransmitters. To analyse the neuronal function of these LGCs, we show that a novel serotonin-gated cation channel, LGC-50, is essential for aversive olfactory learning. lgc-50 mutants show a specific defect in learned olfactory avoidance of pathogenic bacteria, a process known to depend on serotonergic neurotransmission. Remarkably, the expression of LGC-50 in neuronal processes is enhanced by olfactory conditioning; thus, the regulated expression of these receptors at synapses appears to represent a molecular cornerstone of the learning mechanism.

neuroscience↗