Department of Neurobiology; Francis Lab; Graduate School of Biomedical Sciences, Neuroscience Program
Acetylcholine; Aldicarb; Amino Acid Sequence; Animals; Animals, Genetically Modified; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cholinesterase Inhibitors; Cloning, Molecular; Electric Stimulation; Excitatory Postsynaptic Potentials; GABAergic Neurons; Gene Expression Regulation; Green Fluorescent Proteins; Inhibitory Postsynaptic Potentials; Locomotion; Luminescent Proteins; Microscopy, Confocal; Motor Neurons; Movement; Muscle, Skeletal; Mutation; Neural Inhibition; Neuromuscular Junction; Patch-Clamp Techniques; Receptors, Cholinergic
Molecular and Cellular Neuroscience | Neuroscience and Neurobiology
Heterogeneity in the composition of neurotransmitter receptors is thought to provide functional diversity that may be important in patterning neural activity and shaping behavior (Dani and Bertrand, 2007; Sassoe-Pognetto, 2011). However, this idea has remained difficult to evaluate directly because of the complexity of neuronal connectivity patterns and uncertainty about the molecular composition of specific receptor types in vivo. Here we dissect how molecular diversity across receptor types contributes to the coordinated activity of excitatory and inhibitory motor neurons in the nematode Caenorhabditis elegans. We show that excitatory and inhibitory motor neurons express distinct populations of ionotropic acetylcholine receptors (iAChRs) requiring the ACR-12 subunit. The activity level of excitatory motor neurons is influenced through activation of nonsynaptic iAChRs (Jospin et al., 2009; Barbagallo et al., 2010). In contrast, synaptic coupling of excitatory and inhibitory motor neurons is achieved through a second population of iAChRs specifically localized at postsynaptic sites on inhibitory motor neurons. Loss of ACR-12 iAChRs from inhibitory motor neurons leads to reduced synaptic drive, decreased inhibitory neuromuscular signaling, and variability in the sinusoidal motor pattern. Our results provide new insights into mechanisms that establish appropriately balanced excitation and inhibition in the generation of a rhythmic motor behavior and reveal functionally diverse roles for iAChR-mediated signaling in this process.
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DOI of Published Version
Hilary A. Petrash, Alison Philbrook, Marian Haburcak, Belinda Barbagallo, and Michael M. Francis. ACR-12 Ionotropic Acetylcholine Receptor Complexes Regulate Inhibitory Motor Neuron Activity in Caenorhabditis elegans. J Neurosci. 2013 Mar 27;33(13):5524-32. doi: 10.1523/JNEUROSCI.4384-12.2013. Link to article on publisher's site
The Journal of neuroscience : the official journal of the Society for Neuroscience
Petrash, Hilary A.; Philbrook, Alison; Haburcak, Marian; Barbagallo, Belinda; and Francis, Michael M., "ACR-12 ionotropic acetylcholine receptor complexes regulate inhibitory motor neuron activity in Caenorhabditis elegans" (2013). University of Massachusetts Medical School Faculty Publications. 128.