Mossy fiber input to CA3 interneurons: Balancing short term plasticity and regulation by presynaptic receptors.

The hippocampus is a brain structure thought to be critically important for the formation and maintenance of memories. In order do this, the region must process information as both a linear sequence and as discrete events or objects such that representations can be recalled even when the stimulus is incomplete. This is thought to be accomplished in the hippocampus through several streams of serial and parallel processing kept separate and intact by inhibition. These streams of processing take the anatomical form of the three major glutamatergic pathways of the hippocampus: the perforant path, the mossy fibers and the Schaffer collaterals. Inhibition is provided by specialized groups of GABAergic interneurons. Though the hippocampus has been the subject of intense study for decades, there remain populations of cells that are not well understood in terms of their role in the network. Within area CA3, one of these populations is a group of interneurons with soma residing in the str. lacunosum moleculare that provide feedforward inhibition onto CA3 pyramidal cells. The goal of this thesis was to understand the synaptic physiology of mossy fiber (MF) input to str. lacunosum moleculare interneurons (L-Mi), a connection that has been largely overlooked due to skepticism that an interneuron population ~ 250 µm away could be interacting with the MF pathway. The data presented here describe the functional anatomy of the connection, and define the short term synaptic physiology of MF input to L-Mi including an estimate of the quantal amplitude. I have also documented the modulation of this connection by a presynaptic metabotropic glutamate receptor not previously thought to have a role in MF physiology, thus expanding the known repertoire of MF target specificity. Most importantly, however, these data provide a mechanism through which feedforward inhibition onto CA3 pyramidal cells is regulated in the short term, under physiologic stimulus patterns, and contribute to our knowledge of the function of the CA3 network