Negoita, Florenta Aura
(2003)
CELLULAR MECHANISMS UNDERLYING GLUTAMATERGIC CALCIUM RESPONSES IN DEVELOPING AUDITORY BRAINSTEM NEURONS.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Spontaneous and sound-driven activity, glutamatergic synaptic transmission and Ca2+ signaling are critical for formation, maturation, refinement and survival of neuronal circuits including the auditory system. The present study investigated the mechanisms by which glutamatergic inputs from the cochlear nucleus regulate intracellular calcium concentration ([Ca2+]i) in developing lateral superior olive (LSO) neurons, using Ca2+ imaging in fura-2AM labeled brainstem slices.AMPA/kainate receptors primarily mediated Ca2+ responses elicited by single stimuli and contributed to Ca2+ responses elicited by low and high frequency bursts by approximately 75% and 50% respectively. Both AMPAR and kainate receptors were Ca2+ impermeable and increased [Ca2+]i via membrane depolarization and activation of voltage gated calcium channels (VGCCs). NMDARs contributed approximately 50% to Ca2+ responses independent of the stimulus frequency. Their high contribution to Ca2+ responses was consistent with their contribution (30-60%) to EPSPs triggered by stimulation of AVCN-LSO synapses. mGluRs contributed to Ca2+ responses only under high frequency stimulation (>20Hz). Group I mGluR-mediated Ca2+ responses had two components: release from internal stores and influx from the extracellular milieu. The influx was mediated by a channel sensitive to Ni2+, La3+ and 2-APB, consistent with it being a member of the TRP family. During development, the contribution of this channel decreased and it was lost after hearing onset, suggesting that it might be downregulated by auditory experience. In summary, distinct temporal patterns of synaptic activity in the LSO activate distinct GluR types and each receptor type employs a distinct Ca2+ entry pathway. This could possibly lead to activation of distinct intracellular cascades and distinct gene expression programs (West et al., 2001) that may be involved in distinct developmental aspects.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Negoita, Florenta Aura | flnst2@pitt.edu | FLNST2 | |
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| ETD Committee: |
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| Date: |
12 December 2003 |
| Date Type: |
Completion |
| Defense Date: |
18 November 2003 |
| Approval Date: |
12 December 2003 |
| Submission Date: |
10 December 2003 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Neurobiology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
calcium imaging; fura-2AM |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-12102003-130815/, etd-12102003-130815 |
| Date Deposited: |
10 Nov 2011 20:10 |
| Last Modified: |
15 Nov 2016 13:54 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/10267 |
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