All ETDs from UAB

Advisory Committee Chair

Lynn Dobrunz

Advisory Committee Members

Timothy Gawne

Robin Lester

Lori McMahon

Linda Wadiche

Document Type

Dissertation

Date of Award

2008

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Hippocampal CA1 pyramidal neurons integrate and filter spatial, temporal, and sensory information from the entorhinal cortex (EC) for memory storage. Synaptic transmission mediates the processing of incoming information, and recent studies have demonstrated that long-term changes in synaptic strength at CA1 synapses are important for learning and memory. Short-term changes in synaptic strength, occurring on a timescale of milliseconds to minutes, do not require lasting modifications and are rapidly reversible. Termed short-term plasticity, it is known to be important for dynamic gain control of synaptic transmission and neural computation. During late postnatal development, there are extensive developmental changes in rat hippocampus, including changes in short-term plasticity at Schaffer collateral (SC) synapses onto CA1 pyramidal cells. The mechanisms underlying these changes are not known, nor is it known whether developmental changes in short-term plasticity also occur at the distal input to CA1, the Temporoammonic (TA) pathway. I use electrophysiological techniques in acute rat hippocampal slices to elucidate mechanisms underlying developmental changes in shortterm plasticity at SC and TA inputs onto CA1 neurons. SC exhibits a decrease in shortterm facilitation while TA exhibits an increase in short-term facilitation from juveniles to young adults. The mechanisms underlying these opposite developmental changes are pathway-specific. The decrease in short-term facilitation at SC synapses is due to iv synaptic activation of the mGluR1 subtype of metabotropic glutamate receptor and is dependent on GABAB receptors, while the increase in short-term facilitation at TA synapses is due to a decrease in initial release probability. Despite converging trends in short-term plasticity during development, SC remains more facilitated than TA in young adults, suggesting a modulatory role of TA in CA1 output. These experiments provide fundamental information about mechanisms of normal hippocampal development, and form the foundation for future studies on the functional properties and developmental modulation of hippocampal synapses in animal models of learning disorders.

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