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A NOVEL NEURONAL MECHANISM FOR TEMPORAL ORDER DISCRIMINATION
by
Yichun Wei
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(NEUROSCIENCE)
December 2011
Copyright 2011 Yichun Wei
Object Description
| Title | A novel neuronal mechanism for temporal order discrimination |
| Author | Wei, Yichun |
| Author email | yichunwe@usc.edu;yichun.wei@gmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Neuroscience |
| School | College of Letters, Arts And Sciences |
| Date defended/completed | 2011-07-28 |
| Date submitted | 2011-12-13 |
| Date approved | 2011-12-13 |
| Restricted until | 2011-12-13 |
| Date published | 2011-12-13 |
| Advisor (committee chair) | Mel, Bartlett W. |
| Advisor (committee member) |
Hirsch, Judith A., Tjan, Bosco S., Grzywacz, Norberto M. |
| Abstract | Natural signals often flow systematically across an array of biological sensors (e.g. the pattern of optic flow on the retina), leading to ordered stimulation of neighboring sensors within small fractions of a second. As such, the need to distinguish the temporal order in which two neighboring sensors, A and B, have been stimulated is often critical for interpreting the stimulus (e.g. detecting whether motion of an object is toward or away from the animal). A variety of neural mechanisms have been proposed for this task, nearly all involving (1) some form of temporal asymmetry between the A and B input pathways, and (2) a nonlinearity that detects or rejects temporal coincidence (Jeffress 1948; Rall 1964; Borg-Gram and Gryzwacz, 1992; Hassenstein and Reichardt 1956, Borst and Egelhaaf 1989). ❧ In this work we explore a novel biophysical mechanism for temporal order-sensitivity (TOS) based on the distinct properties of AMPA and NMDA conductances in glutamatergic synapses. This mechanism establishes a preference for the stimulus sequence A→B compared to B→A when the A pathway is dominated by a slow NMDA conductance while the B pathway is dominated by a fast AMPA conductance. Using a mathematical approach we identify several key properties of this TOS mechanism: (1) we show why the typical sigmoidal input-output curve due to NMDA channel activation allows the summation nonlinearity and temporal asymmetry between the A and B pathways to be simultaneously maximized; (2) we show that there are two thresholds for NMDA spike activation: A threshold amount of NMDA conductance must be activated, and a threshold membrane voltage must be reached in order to trigger an NMDA spike; (3) we give theoretical expressions for the start and end of the superlinear TOS summation window in time, and show why this window is surprisingly short compared to the typical time course of NMDA channel activation; (4) we show that this TOS mechanism depends on the fast temporal responses of AMPA channels activated in dendrites, and would not work in a lumped cell model; (5) we predict that interactions between AMPA, NMDA, and voltage-dependent Na+ channels in the membrane should increase the robustness of TOS responses; (6) we predict the best absolute and relative dendritic locations for two synaptic pathways to achieve temporal order selectivity; and (7) we predict that feed-forward GABAA-mediated inhibition narrows the time window for superlinear summation without significantly weakening the response nonlinearity. Using compartmental simulations, we verified these effects and predictions by identifying conditions that produce “strong” TOS responses, defined as responses that are (1) superlinear to the preferred ordering A→B, i.e. significantly larger than the sum of the individual responses to A and B; (2) temporally asymmetric, i.e. not responding superlinearly to the non-preferred ordering B→A; and (3) robust, i.e. insensitive to small perturbations in the AMPA and NMDA conductances. Our results give a theoretical basis for understanding temporal order-sensitive summation between two pathways when the priming or “modulatory” pathway (activated first) is dominated by NMDA channels, the trigger or “driver” pathway (activated second) has a strong AMPA component, feed-forward inhibition quickly follows the driver input, the two synaptic pathways are physically commingled on the dendrites relatively close to the soma, and the dendritic membrane contains voltage-dependent Na+ channels. ❧ We explored a possible functional application of this TOS scheme in a model of the retinogeniculate projection onto LGN relay cells, that could allow relay cells to respond more quickly, powerfully, and reliably to visual features that move in and out of their receptive fields within a few milliseconds. |
| Keyword | temporal order; neuronal mechanism; NMDA; dendrite; |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m |
| Contributing entity | University of Southern California |
| Rights | Wei, Yichun |
| Physical access | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@dots.usc.edu |
| Archival file | uscthesesreloadpub_Volume6/etd-WeiYichun-457.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@dots.usc.edu |
| Full text | A NOVEL NEURONAL MECHANISM FOR TEMPORAL ORDER DISCRIMINATION by Yichun Wei A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (NEUROSCIENCE) December 2011 Copyright 2011 Yichun Wei |
