Publication Date

2019-02-15

Availability

Open access

Embargo Period

2019-02-15

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Neuroscience (Medicine)

Date of Defense

2019-01-24

First Committee Member

Kevin M. Collins

Second Committee Member

Laura Bianchi

Third Committee Member

Peter Larsson

Fourth Committee Member

Stephen Roper

Fifth Committee Member

Brock Grill

Abstract

Neuronal activity accompanies synapse formation and maintenance, but how early activity contributes to behavior development is poorly understood. Here, we used the Caenorhabditis elegans egg-laying motor circuit as a model to understand how coordinated circuit activity patterns emerge during development in relation to behavior. The C. elegans egg-laying circuit is a simple neural circuit which develops during the fourth larval stage and drives a two-state behavior in adult animals. The egg-laying circuit comprises two serotonergic Hermaphrodite Specific Neurons (HSNs) and six cholinergic Ventral C neurons which synapse onto vulval muscles that contract to release eggs from the uterus. During L4, the cells of the circuit undergo morphological maturation but how this circuit goes on to develop robust patterns of activity seen in adults remains unclear. Using calcium imaging in behaving animals, we found the HSN neurons and vulval muscles show calcium transients in L4 larvae before egg production. HSN activity in L4 is tonic and lacks the alternating burst/quiescent-firing pattern seen in adults. Egg accumulation in the adult uterus renders the muscles sensitive to HSN input. Sterilization or acute electrical silencing of the vulval muscles inhibits presynaptic HSN activity, and reversal of muscle silencing triggers a homeostatic increase in HSN activity that maintains ~12-15 eggs in the uterus. Finally, the Pertussis Toxin-sensitive G alpha subunit maintains the inactive behavior state by reducing neuronal excitability of the HSN neurons. This work describes how modulation by sensory feedback drives circuit activity and maintains a two-state behavior in a model motor circuit.

Keywords

Neural circuit, development; C. elegans; calcium; serotonin; neuromodulation; behavior

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