Neuromodulation provides a mechanism whereby the nervous system can expand the range of both its responsiveness to afferent signals and its repertoire of efferent responses. Modulation of both input and output properties of the nervous system significantly contributes to the complexity of mammalian behavior. The primary goal of this research project is to use the vasopressin (AVP) neuromodulation of norepinephrine (NE)-induced accumulation of cAMP interaction in the hippocampus as neuromodulatory model to test the hypothesis that in some instances neuromodulatory can serve as a biochemical analog of the associative processes which appear to govern learning and memory. If this postulate is true, then the factors which govern electrophysiological associative processes, namely long-term potentiation, should also hold true for the biochemical analog. To test this hypothesis, five specific aims related to associative processes will be determined over a five year period: (1) Determination of the anatomical and spatial relationship between recognition sites for AVP and NE in the hippocampus? (2) Determination of the temporal relationship between activation of receptors for AVP and NE and the subsequent expression of neuromodulation? (3) Determination of the mechanism underlying the calcium/calmodulin dependency of AVP-induced neuromodulation? (4) Determination of the influence of AVP and NE singly and in combination on the induction of long-term potentiation in the dentate gyrus of the hippocampus? (5) Determination of the effect of AVP and NE singly and in combination on the growth and morphology of cultured hippocampal and dentate gyrus neurons. Information derived from this project will lead to insights which will have significance from basic science, theorectical and applied perspectives.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29MH046036-04
Application #
3475414
Study Section
Neurosciences Research Review Committee (BPN)
Project Start
1990-04-01
Project End
1995-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
4
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Southern California
Department
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Brownson, Elizabeth A; Brinton, Roberta D; Chambers, Kathleen C (2002) Vasopressin content in select brain regions during extinction of a conditioned taste aversion. Brain Res Bull 59:125-34
Brinton, R D; Thompson, R H; Brownson, E A (2000) Spatial, cellular and temporal basis of vasopressin potentiation of norepinephrine-induced cAMP formation. Eur J Pharmacol 405:73-88
Brinton, R D; Yamazaki, R; Gonzalez, C M et al. (1998) Vasopressin-induction of the immediate early gene, NGFI-A, in cultured hippocampal glial cells. Brain Res Mol Brain Res 57:73-85
Diaz Brinton, R (1998) Vasopressin in the mammalian brain: the neurobiology of a mnemonic peptide. Prog Brain Res 119:177-99
Brinton, R D; Gonzalez, T M; Cheung, W S (1994) Vasopressin-induced calcium signaling in cultured hippocampal neurons. Brain Res 667:151-9
Brinton, R D; Monreal, A W; Fernandez, J G (1994) Vasopressin-induced neurotrophism in cultured hippocampal neurons via V1 receptor activation. J Neurobiol 25:380-94
Brinton, R D; Gonzalez, T M; Cheung, W S (1994) Vasopressin-induced calcium signaling in cultured hippocampal neurons. Brain Res 661:274-82
Diaz Brinton, R; Brownson, E A (1993) Vasopressin-induction of cyclic AMP in cultured hippocampal neurons. Brain Res Dev Brain Res 71:101-5
Chen, C; Diaz Brinton, R D; Shors, T J et al. (1993) Vasopressin induction of long-lasting potentiation of synaptic transmission in the dentate gyrus. Hippocampus 3:193-203
Brinton, R E (1990) Neuromodulation: associative and nonlinear adaptation. Brain Res Bull 24:651-8