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.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-03232010-131000 |
| Date | 17 June 2010 |
| Creators | Cosgrove, Kathleen Elizabeth |
| Contributors | Jean-Claude Lacaille, Justin Crowley, Nathan Urban, Alison Barth, German Barrionuevo, Stephen Meriney |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-03232010-131000/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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