The functional roles of dopaminergic modulation and local inhibition in the striatum / Jason T. Moyer.

Format:

Book

Manuscript

Microformat

Thesis/Dissertation

Author/Creator:

Moyer, Jason T.

Contributor:

Margulies, Susan, advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Penn dissertations--Bioengineering.

Bioengineering--Penn dissertations.

Local Subjects:

Penn dissertations--Bioengineering.

Bioengineering--Penn dissertations.

Physical Description:

xii, 175 pages : illustrations ; 29 cm

Production:

2009.

Summary:

The striatum is involved in action selection, habit formation, and learning, as well as a number of highly prevalent diseases---such as Parkinson's disease, schizophrenia, and drug addiction. Despite its clear importance to healthy brain function, relatively little is understood about how the striatum functions, or even what role it specifically performs in the brain. This study uses highly detailed computational models to investigate the integrative properties of the striatal principal cell (the medium spiny neuron, or MSN), the functional role of dopamine in the striatum, and the functional role of inhibition in the straitly network. The first section describes the most detailed, biophysically accurate single cell model of the MSN constructed to date. Specifically, the results in this section show that MSNs are not inherently bistable, that action potentials are able to backpropagate into an MSN's dendrites, and that MSN integration of input is critically dependent on the NMDA:AMPA ratio in the cell. The second section examines the net effects of dopamine (DA) on the MSN. At the whole-cell level, the synaptic effects of DA modulation (i.e., effects on AMPA and NMDA channels) tend to be opposite the intrinsic effects of DA modulation (i.e., effects on sodium, potassium, and calcium channels), suggesting that regulating these whole-cell properties is not the principal function of DA in the striatum. At the dendritic spine level, DA's effects via D1 receptors do act cooperatively to increase calcium influx to the spine, suggesting that DA modulation may principally control MSN synaptic plasticity. The third section describes a large, anatomically accurate network model of the striatum, the first ever developed. This model is used to explore the functionality of two types of inhibition---lateral (MSN-to-MSN) and feedforward (interneuron-to-MSN) inhibition. Lateral inhibition is able to suppress MSN firing and sculpt synchronous MSN firing, while feedforward inhibition seems most likely to desynchronize MSN ensembles, perhaps as part of the action selection mechanism.

Notes:

Adviser: Susan Margulies.

Thesis (Ph.D. in Bioengineering) -- University of Pennsylvania, 2009.

Includes bibliographical references.

Local Notes:

University Microfilms order no.: 3363570.