Although substantial evidence exists for the activity-dependent release of VIP in the CNS, its effect on synaptic function is poorly described. Within the hippocampus, VIP is expressed exclusively in GABAergic interneurons, suggesting that GABA and VIP may inhibitor postsynaptic responses in concert. VIP stimulates the cAMP/PKA pathway via VPAC1 and VPAC2 receptors. Moreover, GABAR beta subunits are substrates of PKA-mediated phosphorylation. Interestingly, our preliminary findings indicate that agents capable of increasing PKA-mediated phosphorylation, including VIP, can restore in vitro GABAR function in the hippocampal CA1 region of benzodiazepine tolerant rats. Using newly available VIP receptor antibodies we propose to describe the anatomical distribution of VPAC1 and VPAC2 in the hippocampus, their overlap with GABA receptors, and the cross-talk between VIP and GABA receptor proteins. We propose, that 1) VPAC1 and VPAC2 receptors reside on CA1 pyramidal cells at sites postsynaptic to VIP containing interneurons; 2) VPAC1 and/or VPAC2 co-localize at these synapses with subunit phosphorylation. These studies are of broad interest as VPAC1 and VPAC2 distribution in the rat CNS, with particular respect to postsynaptic GABA receptors, has not been described. Moreover, elucidating VIP and GABA-ergic interactions may reveal opportunities for the treatment of a variety of GABA receptor dysfunctions, including benzodiazepine tolerance.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30DA014142-03
Application #
6634358
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
2002-03-21
Project End
Budget Start
2003-03-21
Budget End
2004-03-20
Support Year
3
Fiscal Year
2003
Total Cost
$36,686
Indirect Cost
Name
University of Toledo
Department
Physiology
Type
Schools of Medicine
DUNS #
807418939
City
Toledo
State
OH
Country
United States
Zip Code
43614