Project Summary
Learned behavioral preferences enable animals to perform different goal-directed behaviors even when
encountering identical sensory information from the environment. A gap in knowledge remains regarding
how learned behavioral preferences act at the level of single sensory neurons and interneurons to
differentially process information and guide distinct goal directed behaviors. The C. elegans nematode
provides a tractable model to address this question. The overall objective of this proposal is to determine
the synaptic modulatory mechanisms that encode sensory processing and drive the distinct learned
behavioral preference in freely moving C. elegans. As poikilotherms, C. elegans does not have an innate
preferred temperature. Instead it can learn to prefer a temperature when it has been raised in it for four hours
in the presence of food, a behavior known as thermotaxis. Using thermotaxis behavior, this proposal sets to
understand how C. elegans synapses between the thermosensory neuron AFD and its only postsynaptic
partner (AIY) are modulated by experiences to drive a learned temperature preference. The
overarching hypothesis of this proposal, which is based on our preliminary data, is that previous experience
modulates excitatory and inhibitory output from the thermosensory neuron AFD and alters calcium
responses at the interneuron AIY to actuate specific behavioral responses during thermotaxis. The rationale
of the proposed aims is that we can use the compact neural circuitry of C. elegans to dissect how
individual neurotransmitters and receptors, expressed in specific neurons, interact and are modulated by
experience to drive learned behaviors in freely moving animals. The first aim of this proposal will result in
the development of an innovative method that allows simultaneous probing of single neuron calcium activity,
temperature experience and thermotaxis behavior in freely moving animals navigating a temperature
gradient. This approach will assess how experience alters sensory AFD-to-interneuron-AIY synaptic
communication (via calcium imaging) and how modification of this synapse results in the actuation of a
preferred behavior. The second aim will combine this novel approach with CRISPR-based conditional
knockouts to dissect the identity and role of excitatory and inhibitory neurotransmitters, and how they are
modulated by experience in single cells to alter sensory processing and drive the behavioral preferences.
Also, a proposed training plan will allow the PI continue his growth as an independent scientist, and contribute
to diversifying the scientific workforce. Completion of the proposal will vertically advance our knowledge on
how sensory to interneuron modulation encodes a learned preference and coordinates goal-directed
behaviors.
