Regulation of hippocampal pyramidal neuron excitability by subthreshold voltage-dependent conductances
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CitationYamada-Hanff, Jason. 2015. Regulation of hippocampal pyramidal neuron excitability by subthreshold voltage-dependent conductances. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences.
AbstractThe single neuron’s decision of whether to fire an action potential is the central computation underlying neural function. This transformation of synaptic inputs into an output pattern of spikes is controlled by the interaction of synaptic input with the neuron’s intrinsic membrane properties. During this process, the neural membrane is not just a passive receiver of input but reacts dynamically to input via the activity and modulation of ion channels that are active below the action potential threshold. The goal of this work was to examine how such subthreshold voltage-dependent conductances contribute to the electrical function of hippocampal CA1 pyramidal neurons.
Spontaneous firing is a hallmark function of subthreshold inward conductances as they can drive depolarization in the absence of synaptic input. Although CA1 pyramidal neurons usually require input to fire, cholinergic modulation increases their excitability and can elicit spontaneous activity. Chapter 2 explores the ionic mechanisms of this spontaneous firing induced by muscarinic stimulation. Muscarinic modulation activates a current that shifts the entire steady-state current-voltage relationship for the cell so that inward current flows at all subthreshold voltages. This inward shift unveils the activity of a large persistent sodium current which drives depolarization. Using recordings of the cell’s own
firing as a voltage command, I show directly that persistent sodium current, and not hyperpolarization-activated cation current, underlies the slow subthreshold depolarization that drives spontaneous activity in these cells.
The activity of subthreshold voltage-dependent conductances makes the subthreshold membrane an active participant in input integration. In Chapter 3, I explore the contribution of voltage-dependent conductances in the context of natural (and naturalistic) membrane behavior. I show that the subthreshold activity of voltage-dependent conductances confers a voltage dependence on intrinsic membrane properties. Further, to account for time-dependent properties, I directly measure the contribution of persistent sodium current and hyperpolarization-activated current to membrane behavior during a naturalistic stimulus delivered via dynamic clamp, as well as during in vivo membrane behavior.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:14226098
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