Biomedical Sciences ETDs

Publication Date

5-1-2011

Abstract

The processes of vesicular trafficking and membrane fusion are fundamental to nervous system development and communication among neurons within integrated circuits. The regulated release of several neurotransmitters is dependent on synaptosomal-associated protein 25 kDa (SNAP-25)-containing soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) core complexes. The requirement for this fusogenic machinery in evoked neurosecretion has been repeatedly demonstrated through the use of mutant mouse models and neurotoxin blockades. However, the existence of a functional role for a SNAP-25-containing SNARE complex has not been shown in the major inhibitory neurotransmitter system of the brain, gamma-aminobutyric acid (GABA). To determine whether SNAP-25 participates in the evoked GABAergic neurotransmission, we investigated the expression and function of this protein in inhibitory terminals. In addition, we identified the major SNAP-25 isoform expressed by mature GABAergic neurons. The results presented here provide compelling evidence that SNAP-25 is critical for evoked GABA release and is expressed in the presynaptic terminals of mature GABAergic neurons, consistent with its function as a component of a fundamental core SNARE complex required for stimulus-driven neurotransmission. Furthermore, we conclude that SNAP-25b is the predominant isoform expressed in central inhibitory neurons of the adult brain.

Keywords

SNAP-25 presynaptic terminal GABA SNARE glutamatergic synaptic vesicle recycling neurotoxin exocytosis

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Advisor

Wilson, Michael C.

First Committee Member (Chair)

Partridge, Donald

Second Committee Member

Cunningham, Lee Anna

Third Committee Member

Deretic, Dusanka

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