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Title

Action Potential Initiation and Propagation in Dentate Gyrus Granule Neurons

Date of Award

Spring 8-15-2009

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Neurosciences)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

Axonal action potentials initiate the cycle of synaptic communication that is key to our understanding of nervous system functioning. The field has accumulated vast knowledge of the signature action potential waveform, firing patterns, and underlying channel properties of many cell types, but in most cases this information comes from somatic intracellular/whole-cell recordings, which necessarily measure a mixture of the currents compartmentalized in the soma, dendrites, and axon. In this thesis, I aim to directly probe the axon of dentate granule (DG) neurons to determine properties of action potential initiation and propagation. DG neurons give rise to some of the smallest unmyelinated fibers in the mammalian CNS, the hippocampal mossy fibers. These neurons are also key regulators of physiological and pathophysiological information flow through the hippocampus.

We have found several interesting and unknown aspects of DG action potentials that may contribute to their low-pass filtering properties. DG neurons exhibited axonal action potential initiation significantly more proximal than CA3 pyramidal neurons, suggested by phase plot analysis of somatic action potentials and by local tetrodotoxin application to the axon and somatodendritic compartments. This conclusion was also verified by immunostaining for voltage-gated sodium channel subunits and by direct dual soma/axonal recordings. We also uncovered that DG neurons exhibited a significantly higher action potential voltage threshold and slower axonal conduction velocity than CA3 neurons.

Upon closer investigation of the DG depolarized action potential voltage threshold, we find no evidence that tonic GABA currents, leak or voltage-gated potassium conductances, or the expression of sodium channel isoform differences can explain this depolarized threshold. In silico simulations of DG and CA3 pyramidal neurons revealed that the cell morphology and sodium channel distribution combine to yield the characteristic DG neuron action potential upswing and voltage threshold. Proximal axon sodium channel distribution strongly contributes to the higher voltage threshold of DG neurons. Our results suggest that the proximal location of axon sodium channel in DG neurons contributes to the intrinsic excitability differences between DG and CA3 neurons and may participate in the low-pass filtering function of DG neurons.

Language

English (en)

Chair and Committee

Steven Mennerick

Committee Members

Aaron DiAntonio, Jim Huettner, Peter Lukasiewicz, Joe Henry Steinbach, Thomas Woolsey

Comments

Permanent URL: https://doi.org/10.7936/K7N014GF

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