Electrical activity and calcium signaling have significant roles in directing neurotransmitter specification. Changes in electrical activity by natural visual stimuli trigger the appearance of neurotransmitters in neurons that normally produce different ones. Many of studies of these processes have been carried out in cell culture, providing important insights into the capabilities of developing neurons. Ultimately, however, we want to understand how differentiation proceeds in vivo. The proposed research has three specific aims, focused on understanding these processes in the intact nervous system of larvae of the frog, Xenopus laevis, which facilitates behavioral, cellular and molecular analysis. The immediate goal of this research is to test the hypothesis that activation of a neural circuit by a natural olfactory stimulus leads to transmitter respecification in neurons in the circuit with corresponding changes in behavior controlled by the activated circuit, and that specific molecular mechanisms are involved. The long- term goal of this research is to understand how neural network activation can be used to induce neurotransmitter plasticity in the brain.

Public Health Relevance

Electrical activity and calcium signaling have significant roles in directing neurotransmitter specification. Changes in electrical activity by natural visual stimui trigger the appearance of neurotransmitters in neurons that normally produce different ones. Most studies of these processes have been carried out in cell culture;ultimately, however, we want to understand how differentiation proceeds in vivo. Here we propose to determine whether activation of a neural circuit by a natural olfactory stimulus leads to transmitter respecificationin the intact animal, with changes in behavior, and to identify the molecular mechanisms involved. Understanding the molecular mechanisms may allow therapeutic interventions.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
2R01NS057690-04A1
Application #
8693211
Study Section
Neurodifferentiation, Plasticity, and Regeneration Study Section (NDPR)
Program Officer
Morris, Jill A
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Plazas, Paola V; Nicol, Xavier; Spitzer, Nicholas C (2013) Activity-dependent competition regulates motor neuron axon pathfinding via PlexinA3. Proc Natl Acad Sci U S A 110:1524-9
Demarque, Michael; Spitzer, Nicholas C (2012) Neurotransmitter phenotype plasticity: an unexpected mechanism in the toolbox of network activity homeostasis. Dev Neurobiol 72:22-32
Spitzer, Nicholas C (2012) Activity-dependent neurotransmitter respecification. Nat Rev Neurosci 13:94-106