Biomedical Sciences ETDs

Publication Date

5-1-2010

Abstract

Following a presynaptic action potential, there is a rapid rise of [Ca2+]i in the immediate vicinity of Ca2+ channels that triggers membrane fusion and release of transmitter from vesicles within this microdomain. This presynaptic Ca2+ signal ([Ca2+]pre) then disperses to produce a residual Ca2+ ([Ca2+]res) that decays over the course of tens to hundreds of milliseconds. The [Ca2+]res has important implications in synaptic plasticity and is the basis for working memory storage. Ultimately [Ca2+]res is removed from the cytoplasm either into intracellular organelles or across the plasma membrane into the extracellular environment. Calcium influx pathways, cytoplasmic Ca2+ buffering proteins, and Ca2+ extrusion processes in rodent neurons undergo considerable change during the first postnatal month. These changes have important functional significance in short-term plasticity — in particular paired-pulse facilitation (PPF) — at presynaptic terminals where neurotransmitter release is directly dependent on the dynamics of free cytoplasmic Ca2+. To examine developmental changes in [Ca2+]res dynamics in the Schaffer collateral synapses onto CA1 pyramidal neurons in in vitro hippocampal slices, we measured the timecourse of decay of [Ca2+]res in presynaptic terminals following single and paired orthodromic stimuli in the stratum radiatum. The contribution of the slow component compared to the total decay of [Ca2+]res was reduced from >80% in newborn mice to ~50% in the more mature animals (>P24) and [Ca2+]res had a distinct slow rising component in newborn mice (

Keywords

calcium, hippocampus

Sponsors

National Science Foundations NSF-DGE-0549500 National Institute of Health NIH-RO1-MH48989 NIH-R01-MH07386

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Advisor

Partridge, L. Donald

Second Advisor

Wilson, Michael

First Committee Member (Chair)

Thomas, James

Second Committee Member

Hartley, Rebecca

Third Committee Member

Shuttleworth, C. William

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