Quantal analysis is the most powerful electrophysiological tool available for identifying the nature of altered synaptic function. Recently several laboratories using quantal analysis techniques have arrived at partially opposite conclusions concerning the mechanism of hippocampal long-term synaptic enhancement. Discrepancies may be due to differences in the methods of analysis and data selection or experimental variables including the developmental state of the hippocampus. The objective of this project is an understanding of biophysiological mechanisms underlying observed changes in synaptic transmission properties. The primary hypothesis under consideration is that various mechanisms for altered synaptic function are differently expressed during development and maturation. While transmission properties of adult synapses are adequately described by a simple binomial function, this model may not be appropriate for neonatal synapses. Therefore, a major portion of the first study is dedicated to ascertaining the proper model to describe transmission for pairs of synaptically connected CA3-CA1 cells. The distribution of intracellularly recorded unitary postsynaptic responses elicited by intracellular presynaptic activation will be examined using several models with various levels of constraint in order to determine the model which is appropriate for extraction of quantal parameters. After data collection for quantal analysis, cell pairs will be labeled with dye in order to obtain electrophysiological/morphological correlations. In addition to dual impalement, unitary responses will be obtained using afferent minimal-stimulation in order to investigate the nature of increased synaptic efficacy occurring over the course of development. Minimal-stimulation facilitates the collection of a considerable quantity of data and permits examination of paired-pulse facilitation through the precise timing of synaptic activation. In addition to quantal analysis of paired-cells and minimal-stimulation, proposed experiments will examine several extracellular measurements including the ratio of EPSP to fiber potential amplitudes and EPSP to stimulation intensity ratios. A second study will employ these techniques to explore the nature of altered synaptic efficacy of adult rats differentially exposed to complex environments. Proposed studies will combine intracellular recording techniques with morphological correlations in the rat hippocampal slice preparation to determine the transmission model which best describes synaptic function for neonatal and adult synapses and how transmission parameters change during development or as a result of experience. The overall project is expected to provide data which will aid in the construction of models concerning brain mechanisms underlying synaptic plasticity during development and the role of the synapse in information storage.
