Dendrites are classically regarded as the brains listeners, while neuronal output is thought to be the exclusive privilege of the axon. Although we now appreciate the complexity of dendritic integration, the role of dendrites as output structures has received less attention. This is becoming an increasingly important topic, as the list of cell types with release competent dendrites continues to grow.
One boon of coupling dendritic activity to dendritic release is that outputs from a single neuron typically thought to occur from fixed sites with stereotyped dynamics may occur for signals of varying spatial extent, timecourse, and release efficacy. In essence, dendritic output may inherit the same diversity characteristic of events in excitable dendrites. Here I studied dendritic transmitter output and its modulation in cells of the accessory olfactory bulb a CNS structure critical for processing species-specific chemical signals called pheromones. Because of the stereotypy of its inputs, the prevalence of dendritic transmitter release from its cells, and its well-defined outputs, the AOB offers a superb model system for studying the integrative and output properties of dendrites.
I first characterized basic excitable properties of the apical dendrites of mitral cells (the principal AOB neurons), and observed that they conduct non-decremental action potentials (APs). In addition to APs, these dendrites were also found to support compartmentalized, synaptically-evoked calcium spikes. Both APs and local spikes were triggers of dendritic glutamate release and feedback inhibition, suggesting that neuronal output can be flexibly routed to particular populations of postysynaptic cells. I next asked whether the relative efficacy of particular dendritic events as triggers of transmitter release can be altered, as this could provide an additional level of control over single neuron output. I found that metabotropic glutamate receptors (mGluRs) play a key role in controlling dendritic output from AOB mitral cells and an obligatory role in concomitant feedback inhibition. This work culminates with the demonstration of a new principle of neuronal signaling: the ability of mGluRs to gate a transition between phasic and tonic dendritic transmitter release. Taken in total, these results extend our understanding of how the outputs from single neurons are controlled.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-04222008-103440 |
| Date | 10 June 2008 |
| Creators | Castro, Jason Brian |
| Contributors | Bard Ermentrout, Justin Crowley, Gordon Shepherd, Steve Meriney, Nathan Urban, Karl Kandler |
| 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-04222008-103440/ |
| Rights | unrestricted, 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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