? The broadest objective of the proposed research is to characterize the changes in synaptic signaling that accompany increases and decrease in electrical activity. Chronic exposure to drugs of abuse such as ethanol, barbiturates, and benzodiazepines causes a downregulation in electrical activity, which ultimately leads to neuronal death. The goal of Aim 1 is to determine whether this decrease in neuronal activity results in reduced neurotransmitter release because of drug effects on Ca2+ currents, or in enhanced neurotransmitter release through initiation of homeostatic mechanisms. Such changes in synaptic signaling could either lessen or intensify the effects of drugs of abuse on neuronal survival. The goal of Aim 2 is to determine the effects on synaptic signaling caused by mimicking increased electrical activity with K+ depolarization. Preliminary data indicate that depolarization curtails development of glutamatergic synapses, while leaving inhibitory currents intact. Experiments will be conducted to distinguish whether a presynaptic and a postsynaptic mechanism accounts for this effect of K+ on excitatory currents.
Both Aim 1 and Aim 2 will utilize whole-cell, patch-clamp techniques in a hippocampal microculture paradigm, which will facilitate examination of synaptic electrophysiology. ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DA015948-02
Application #
6665381
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
2003-02-01
Project End
2004-04-30
Budget Start
2004-02-01
Budget End
2004-04-30
Support Year
2
Fiscal Year
2004
Total Cost
$13,608
Indirect Cost
Name
Washington University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Crawford, Devon C; Jiang, Xiaoping; Taylor, Amanda et al. (2012) Differential requirement for protein synthesis in presynaptic unmuting and muting in hippocampal glutamate terminals. PLoS One 7:e51930
Moulder, Krista L; Mennerick, Steven (2005) Reluctant vesicles contribute to the total readily releasable pool in glutamatergic hippocampal neurons. J Neurosci 25:3842-50
Moulder, Krista L; Meeks, Julian P; Shute, Amanda A et al. (2004) Plastic elimination of functional glutamate release sites by depolarization. Neuron 42:423-35