The function of the nervous system depends on the appropriate specification of neurotransmitters and their receptors that enable the function of neural circuits. We have discovered that circuit activity plays a key role in transmitter specification (Dulcis and Spitzer, 2008;Dulcis et al., 2013) and that changes in transmitter expression are matched by corresponding changes in postsynaptic receptors (Borodinsky &Spitzer, 2007;Dulcis &Spitzer, 2008;Dulcis et al., 2013), causing changes in behaviors. We now propose to determine whether neurotransmitter switching can be induced by patterns of neuronal activity that induce LTP in the adult rat hippocampus, and whether this is accompanied by changes receptor population. We will also determine whether environmental enrichment and fear conditioning that engage the hippocampus induce neurotransmitter switching. We will test the role of newly expressed transmitters in adult neurogenesis and in the development of resilience to acute and chronic stress. The immediate goal of this research is to test the hypothesis that activation of neural circuits in the hippocampus leads to transmitter respecification in neurons in these circuits, with corresponding changes in adult neurogenesis and/or stress behavior. A long-term goal is to understand how neural network activation can be used to induce neurotransmitter plasticity in the adult brain and ultimately to advance the mission of the NIH to treat neurological disorders.

Public Health Relevance

The function of the nervous system depends on the appropriate specification of neurotransmitters and their receptors that enable the function of neural circuits. Previous studies of transmitter switching have focused principally on the spinal cord and hypothalamus and the extent of this form of plasticity is unknown. The hippocampus is important for learning and memory;here we investigate neurotransmitter switching and its function in hippocampal plasticity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21MH105706-01
Application #
8806924
Study Section
Neurodifferentiation, Plasticity, and Regeneration Study Section (NDPR)
Program Officer
Asanuma, Chiiko
Project Start
2014-09-10
Project End
2016-08-31
Budget Start
2014-09-10
Budget End
2015-08-31
Support Year
1
Fiscal Year
2014
Total Cost
$183,155
Indirect Cost
$58,155
Name
University of California San Diego
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093