Biology subjects

Ardiel, E. L.

Publications and source records attributed to Ardiel, E. L..

4 recordsLinked to original sources

bioRxiv2025

Immature C. elegans motor neurons control early embryo behavior via both synaptic and non-synaptic GABA release

Pre-natal brain activity has long lasting effects on subsequent neurodevelopment. It is unclear if early brain activity is dominated by cell intrinsic, synaptic, or non-synaptic mechanisms. We address this question by analyzing C. elegans embryo behavior in snf-11 mutants, which lack a plasma membrane GABA re-uptake pump (orthologous to GAT1). At 510-570 minutes post-fertilization, embryo motion was transiently and potently inhibited in snf-11 GAT1 mutants, which precedes formation of most nerve ring synapses. This transient motion inhibition requires GABA synthesis in DD motor neurons and UNC-49 GABAA receptors in body muscles. When motion inhibition occurs, DD neurons have not yet completed neurite outgrowth. Genetic analysis suggests that motion inhibition was mediated by both synaptic and tonic GABA release from DD motor neurons. These results suggest that DD neurons control embryo behavior prior to completing their developmental maturation. Significance StatementLittle is known about how prenatal circuits control embryo behavior. We show that the motion of early C. elegans embryos is transiently inhibited by immature GABAergic motor neurons that have not yet completed neurite outgrowth. GABAs inhibitory effect on early embryo behavior occurs before most synapses have formed in the worms central neuropil. For this early behavior, we find that synaptic GABA release plays a minor role while non-synaptic mechanisms predominate. Our results suggest that non-synaptic forms of GABA transmission play a significant role in prenatal circuits.

neuroscience↗

bioRxiv2021

Systematic analysis of C. elegans embryo behavior reveals a stereotyped developmental progression and a rhythmic pattern of behavioral quiescence

AO_SCPLOWBSTRACTC_SCPLOWSystematic analysis of rich behavioral recordings is being used to uncover how circuits encode complex behaviors. Here we apply this approach to embryos. What are the first embryonic behaviors and how do they evolve as early neurodevelopment ensues? To address these questions, we present a systematic description of behavioral maturation for Caenorhabditis elegans embryos. Posture libraries were built using a genetically encoded motion capture suit imaged with light-sheet microscopy and annotated using custom tracking software. Analysis of cell trajectories, postures, and behavioral motifs revealed a stereotyped developmental progression. Early movement is dominated by flipping between dorsal and ventral coiling, which gradually slows into a period of reduced motility. Late-stage embryos exhibit sinusoidal waves of dorsoventral bends, prolonged bouts of directed motion, and a rhythmic pattern of pausing, which we designate slow wave twitch (SWT). Synaptic transmission is required for late-stage motion but not for early flipping nor the intervening inactive phase. A high-throughput behavioral assay and calcium imaging revealed that SWT is elicited by the rhythmic activity of a quiescence-promoting neuron (RIS). Similar periodic quiescent states are seen prenatally in diverse animals and may play an important role in promoting normal developmental outcomes.

neuroscience↗

bioRxiv2021

Shank promotes action potential repolarization by recruiting BK channels to calcium nanodomains

Mutations altering the scaffolding protein Shank are linked to several psychiatric disorders, and to synaptic and behavioral defects in mice. Among its many binding partners, Shank directly binds CaV1 voltage activated calcium channels. Here we show that the C. elegans SHN-1/Shank promotes CaV1 coupling to calcium activated potassium channels. Mutations inactivating SHN-1, and those preventing SHN-1 binding to EGL-19/CaV1 all increase action potential durations in body muscles. Action potential repolarization is mediated by two classes of potassium channels: SHK-1/KCNA and SLO-1 and SLO-2 BK channels. BK channels are calcium-dependent, and their activation requires tight coupling to EGL-19/CaV1 channels. SHN-1s effects on AP duration are mediated by changes in BK channels. In shn-1 mutants, SLO-2 currents and channel clustering are significantly decreased in both body muscles and neurons. Finally, increased and decreased shn-1 gene copy number produce similar changes in AP width and SLO-2 current. Collectively, these results suggest that an important function of Shank is to promote nanodomain coupling of BK with CaV1.

neuroscience↗

bioRxiv2017

CaMK (CMK-1) and O-GlcNAc transferase (OGT-1) modulate mechanosensory responding and habituation in an interstimulus interval-dependent manner in Caenorhabditis elegans

The ability to learn is an evolutionarily conserved adaptation that remains incompletely understood. Genetically tractable model organisms facilitate mechanistic explanations of learning that span genetic, neural circuit, and behavioural levels. Many aspects of neural physiology, including processes that underlie learning (e.g. neurotransmitter release and long-lasting changes in synaptic strength), are regulated by brief and local changes in [m] levels of free intracellular Ca2+. On this scale, changes in [Ca2+] activate many Ca2+-sensors, including the Ca2+/calmodulin-dependent kinases (CaMKs). Here we reveal that the Caenorhabditis elegans ortholog of CaMK1/4, CMK-1, functions in primary sensory neurons to regulate responses to mechanical stimuli and behavioral plasticity, specifically habituation, a conserved form of non-associative learning. The habituation phenotypes of cmk-1 mutants were dependent on interstimulus interval (ISI), such that CMK-1 slows habituation at short ISIs, but promotes it at long ISIs. We predicted potential CaMK phosphorylation targets from catalytic site analysis of the human and C. elegans CaMKs and mutant analysis of these candidates implicated O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, in mechanosensitivity and learning. Cell specific rescue and knockdown experiments showed that both CMK-1 and OGT-1 function cell autonomously in mechanosensory neurons to modulate learning. Interestingly, despite their similar mutant phenotypes, detailed behavioral analysis of double mutants demonstrated that CMK-1 and OGT-1 act in parallel genetic pathways. Our research identifies CMK-1 and OGT-1 as co-expressed yet independent regulators of mechanosensitivity and learning.

animal behavior and cognition↗