Differences in glutamatergic transmission onto interneurons and pyramidal cells in the rat hippocampus

Abstract

In the human brain there are about 100 billion excitatory glutamatergic neurons and 10 billion inhibitory GABAergic neurons. During development, these neurons are synaptically wired together into neural networks, functionally prepared to perform the full register of brain functions, and to learn from experiences. Much research has focused on the understanding of synapses onto excitatory neurons. Considerably less, however, is known about the properties of synapses onto the inhibitory neurons, information necessary to achieve a more complete picture of network function. The aim of this thesis was to examine the effects of glutamate on inhibitory interneurons by comparing them to those on excitatory pyramidal cells in the same region of the hippocampus. Electrophysiological methods were used in the acute rat hippocampal slice preparation. This thesis shows that glutamate synapses formed onto interneurons, in contrast to those formed onto pyramidal cells maintain a developmental phenotype into adulthood. First, interneurons in adult rats have AMPA silent synapses, which are created by activity dependent AMPA silencing. Second, the average number of synapses connecting a presynaptic excitatory cell and an interneuron remains only one in the adult rat. Furthermore, inhibitory interneurons rely more on tonically active extrasynaptic NMDA receptors for their excitability than do excitatory pyramidal cells. The findings presented in this thesis suggest that some fundamental aspects of glutamate transmission onto interneurons do not change during development, as they do in synapses onto pyramidal cells. This differential development results in different phenotypes of glutamatergic transmission onto these two major groups of neurons. This difference is likely critical for the optimized functioning of the adult neural network.