Psychology
UNC-53/NAV-2 Limits Acetylcholine Transmission in Caenorhabditis elegans
Document Type
Poster Presentation
Location
Indianapolis, IN
Subject Area
Psychology
Start Date
11-4-2014 12:00 PM
End Date
11-4-2014 12:59 PM
Sponsor
Christine Noria (Goshen College)
Description
The subcellular events at synapses are important to many biopsychological disorders, including schizophrenia (Fung et al., Biological Psychiatry, 2011). The nematode Caenorhabditis elegans is an excellent model for studies of neurotransmission because of the ease of its genetics and that it is amenable to pharmacological manipulation. unc-53 is the nematode homolog of the Neuron Navigators (Nav-1,2,3), a family of genes that modulate the cytoskeleton during neural development. While a developmental role for unc-53 and the Navs is known, their function in the nervous system after development is complete is not well defined. Nav3 mRNA localizes to synaptic junctions (Kishi et al., J Cell Biol, 2005), and a reduced expression of Nav1 mRNA is associated with neuronal plasticity and cytoskeletal modification among schizophrenic patients (Fung et al., Biological Psychiatry, 2011). We used a pharmacogenic approach to determine if unc-53 functions synaptically in C. elegans by exposing worms to the Acetylcholinesterase inhibitor Aldicarb and the GABA antagonist Pentylenetetrazole (PTZ). Following 1hr exposure to 1mM Aldicarb, significantly more unc-53 (n152) animals were paralyzed (52.3%, n=170, P<0.05) compared to wild-type (15.2%, n=140). Additionally, while some slowing was observed in unc-53 (n152) animals exposed to PTZ at >1hr exposure, the convulsions characteristic of lost GABA function were not observed in unc-53 (n152) (0%, n=145), in contrast to the known GABAergic mutants unc-25 (e156) (93.1%, n=145, P<0.05). Taken together, these results suggest that unc-53 limits acetylcholine transmission and does not affect GABA signaling. Experiments aimed to uncover postsynaptic and presynaptic changes unc-53 mutants are underway.
UNC-53/NAV-2 Limits Acetylcholine Transmission in Caenorhabditis elegans
Indianapolis, IN
The subcellular events at synapses are important to many biopsychological disorders, including schizophrenia (Fung et al., Biological Psychiatry, 2011). The nematode Caenorhabditis elegans is an excellent model for studies of neurotransmission because of the ease of its genetics and that it is amenable to pharmacological manipulation. unc-53 is the nematode homolog of the Neuron Navigators (Nav-1,2,3), a family of genes that modulate the cytoskeleton during neural development. While a developmental role for unc-53 and the Navs is known, their function in the nervous system after development is complete is not well defined. Nav3 mRNA localizes to synaptic junctions (Kishi et al., J Cell Biol, 2005), and a reduced expression of Nav1 mRNA is associated with neuronal plasticity and cytoskeletal modification among schizophrenic patients (Fung et al., Biological Psychiatry, 2011). We used a pharmacogenic approach to determine if unc-53 functions synaptically in C. elegans by exposing worms to the Acetylcholinesterase inhibitor Aldicarb and the GABA antagonist Pentylenetetrazole (PTZ). Following 1hr exposure to 1mM Aldicarb, significantly more unc-53 (n152) animals were paralyzed (52.3%, n=170, P<0.05) compared to wild-type (15.2%, n=140). Additionally, while some slowing was observed in unc-53 (n152) animals exposed to PTZ at >1hr exposure, the convulsions characteristic of lost GABA function were not observed in unc-53 (n152) (0%, n=145), in contrast to the known GABAergic mutants unc-25 (e156) (93.1%, n=145, P<0.05). Taken together, these results suggest that unc-53 limits acetylcholine transmission and does not affect GABA signaling. Experiments aimed to uncover postsynaptic and presynaptic changes unc-53 mutants are underway.