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Dendritic neurotransmitter release and its modulation in accessory olfactory bulb circuits

Castro, Jason Brian (2008) Dendritic neurotransmitter release and its modulation in accessory olfactory bulb circuits. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Dendrites are classically regarded as the brain's "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.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Castro, Jason Brianjasonc@pitt.eduJASONC
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairUrban,
Committee MemberErmentrout, Bardbard@math.pitt.eduBARD
Committee MemberShepherd,
Committee MemberCrowley,
Committee MemberKandler, Karlkkarl@pitt.eduKKARL
Committee MemberMeriney, Stevemeriney@bns.pitt.eduMERINEY
Date: 10 June 2008
Date Type: Completion
Defense Date: 10 March 2008
Approval Date: 10 June 2008
Submission Date: 22 April 2008
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Neuroscience
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: neuronal excitability; odor; olfaction; pheromone; synapse
Other ID:, etd-04222008-103440
Date Deposited: 10 Nov 2011 19:40
Last Modified: 15 Nov 2016 13:41


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