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The Physiology and Computation of Pyramidal Neurons

Citation

Shai, Adam S. (2016) The Physiology and Computation of Pyramidal Neurons. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z92R3PMW. https://resolver.caltech.edu/CaltechTHESIS:01042016-124746578

Abstract

A variety of neural signals have been measured as correlates to consciousness. In particular, late current sinks in layer 1, distributed activity across the cortex, and feedback processing have all been implicated. What are the physiological underpinnings of these signals? What computational role do they play in the brain? Why do they correlate to consciousness? This thesis begins to answer these questions by focusing on the pyramidal neuron. As the primary communicator of long-range feedforward and feedback signals in the cortex, the pyramidal neuron is set up to play an important role in establishing distributed representations. Additionally, the dendritic extent, reaching layer 1, is well situated to receive feedback inputs and contribute to current sinks in the upper layers. An investigation of pyramidal neuron physiology is therefore necessary to understand how the brain creates, and potentially uses, the neural correlates of consciousness. An important part of this thesis will be in establishing the computational role that dendritic physiology plays. In order to do this, a combined experimental and modeling approach is used.

This thesis beings with single-cell experiments in layer 5 and layer 2/3 pyramidal neurons. In both cases, dendritic nonlinearities are characterized and found to be integral regulators of neural output. Particular attention is paid to calcium spikes and NMDA spikes, which both exist in the apical dendrites, considerable distances from the spike initiation zone. These experiments are then used to create detailed multicompartmental models. These models are used to test hypothesis regarding spatial distribution of membrane channels, to quantify the effects of certain experimental manipulations, and to establish the computational properties of the single cell. We find that the pyramidal neuron physiology can carry out a coincidence detection mechanism. Further abstraction of these models reveals potential mechanisms for spike time control, frequency modulation, and tuning. Finally, a set of experiments are carried out to establish the effect of long-range feedback inputs onto the pyramidal neuron. A final discussion then explores a potential way in which the physiology of pyramidal neurons can establish distributed representations, and contribute to consciousness.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:consciousness; dendrites; pyramidal neuron; layer 5; cortex; feedback
Degree Grantor:California Institute of Technology
Division:Biology and Biological Engineering
Major Option:Neurobiology
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Meister, Markus
Thesis Committee:
  • Meister, Markus (chair)
  • Koch, Christof
  • Anastassiou, Costas
  • Gradinaru, Viviana
  • Tsao, Doris Y.
Defense Date:8 December 2015
Funders:
Funding AgencyGrant Number
Swiss National Science FoundationNINDS Grant NS 074015
G. Harold & Leila Y. Mathers Charitable FoundationUNSPECIFIED
Human Frontiers Science ProgramGrant RGP0032/ 2011
Whitaker International ProgramUNSPECIFIED
National Science Foundation Graduate Research FellowshipUNSPECIFIED
Paul G. Allen and Jody AllenUNSPECIFIED
Record Number:CaltechTHESIS:01042016-124746578
Persistent URL:https://resolver.caltech.edu/CaltechTHESIS:01042016-124746578
DOI:10.7907/Z92R3PMW
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:9354
Collection:CaltechTHESIS
Deposited By: Adam Shai
Deposited On:11 Jan 2016 23:17
Last Modified:04 Oct 2019 00:11

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