Department of Neurobiology; Alkema Lab
First Thesis Advisor
Mark J. Alkema
nervous system, locomotion, escape response, Caenorhabditis elegans
Dissertations, UMMS; Caenorhabditis elegans; Connectome; Interneurons; Motor Neurons; Neurons; Locomotion; Neurotransmitter Agents; Optogenetics
How does a nervous system orchestrate compound behaviors? Finding the neural basis of behavior requires knowing which neurons control the behavior and how they are connected. To accomplish this we measured and manipulated neural activity in a live, behaving animal with a completely defined connectome. The C. elegans escape response is a compound behavior consisting of a sequence of behavioral motifs. Gentle touch induces a reversal and suppression of head movements, followed by a deep turn allowing the animal to navigate away from the stimulus. The connectome provides a framework for the neural circuit that controls this behavior. We used optical physiology to determine the activity patterns of individual neurons during the behavior. Calcium imaging of locomotion interneurons and motor neurons reveal unique activity profiles during different motifs of the escape response. Furthermore, we used optogenetics and laser ablations to determine the contribution of individual neurons to each motif. We show these that the suppression of head movements and turning motifs are distinct motor programs and can be uncoupled from the reversal. The molecular mechanisms that regulate these motifs involve from signaling with the neurotransmitter tyramine. Tyramine signaling and gap junctions between locomotion interneurons and motor neurons regulate the temporal orchestration of the turning motif with the reversal. Additionally, tyramine signaling through a GPCR in GABAergic neurons facilitates the asymmetric turning during forward viii locomotion. The combination of optical tools and genetics allows us to dissect a how a neural circuit converts sensory information into a compound behavior.
Clark, CM. Neural Orchestration of the C. elegans Escape Response: A Dissertation. (2014). University of Massachusetts Medical School. GSBS Dissertations and Theses. Paper 750. DOI: 10.13028/M24S4T. http://escholarship.umassmed.edu/gsbs_diss/750
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Calcium activity in neurons during the escape response in a live, behaving animal.
II-2.mov (47411 kB)
Calcium activity in muscles during the escape response in a live, behaving animal.
II-3.mov (184221 kB)
Optogenetic activation of the ALM and AVM.
II-4.mov (854 kB)
Optogenetic activation of the AVA.
II-5.mov (14185 kB)
Optogenetic activation of the RIM.
II-6.mov (14138 kB)
Optogenetic activation of the AVA and inhibition of the AVB.
II-7.mov (14554 kB)
Optogenetic induction of the ventral bend.
II-8.mov (15742 kB)
Optogenetic activation of the AIB.
II-9.mov (1601 kB)
Optogenetic activation of the ALM and AVM and inhibition of the RIV.
II-10.mov (14176 kB)
Activation of the RIM in animals expressing a tyramine-gated anion channel.
II-11.mov (4703 kB)
Activation of the RIM in animals expressing a tyramine-gated cation channel.
III-1.mov (8533 kB)
Laser ablation of the DD GABAerigic motor neurons results in a dorsal bias during forward locomotion.
III-2.mov (10274 kB)
Laser ablation of the VD GABAerigic motor neurons results in a ventral bias during forward locomotion.
III-3.mov (4731 kB)
Tracking of a [Pflp-13::ChR2; Pflp-13::NpHr] single worm’s locomotion and spatial illumination of the ventral nerve cord.
III-4.mov (7417 kB)
A wild-type animal executing a complete omega turn in response to an anterior touch.
III-5.mov (6021 kB)
A ser-2 mutant animal does not execute a complete omega turn in response to an anterior touch.
AI-1.mov (679 kB)
C. elegans L2 larvae getting caught by a constricting ring of D. doedycoides.
AI-2.mov (21304 kB)
C. elegans L2 larvae entering and escaping from a constricting ring of D. doedycoides