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Dopaminergic modulation of entorhinal cortex function

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Dopaminergic modulation of entorhinal cortex function

Caruana, Douglas A (2008) Dopaminergic modulation of entorhinal cortex function. PhD thesis, Concordia University.

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Abstract

The neurotransmitter dopamine has been shown to play an important role in the mnemonic functions of the prefrontal cortex, but it is unclear how dopamine may affect sensory and mnemonic processing in the entorhinal cortex. Midbrain dopamine neurons project to the superficial layers of the lateral entorhinal cortex and may modulate olfactory inputs that also terminate in this area. In awake rats, increasing extracellular dopamine levels in the entorhinal cortex with a selective dopamine reuptake inhibitor facilitated basal synaptic transmission in piriform cortex inputs to layer II. Experiments in slices of the entorhinal cortex maintained in vitro demonstrated concentration-dependent, bidirectional effects of dopamine on synaptic responses; a low 10 oM concentration of dopamine enhanced synaptic responses and higher concentrations of 50 and 100 oM dopamine suppressed responses. The facilitation of responses was dependent on activation of D 1 receptors and the suppression was dependent on D 2 receptors. Intracellular recordings of mixed and isolated synaptic responses demonstrated that the dopaminergic suppression is mediated by a D 2 receptor-dependent reduction in glutamate release and a D 1 -dependent drop in cellular input resistance. The drop in input resistance was mediated by a D 1 receptor-dependent K + conductance. In additional experiments, patterned stimulation of the piriform cortex that induces persistent changes in synaptic strength in the entorhinal cortex was used to assess the effects of dopamine on mechanisms of synaptic plasticity in awake rats. Long-term potentiation and depression were successfully induced in control animals, but the same stimulation protocols failed to alter synaptic function in animals treated with a dopamine reuptake inhibitor. The effects of depleting dopamine in the entorhinal cortex on olfactory memory were also assessed using an olfactory non-match-to-sample task. Rats with 6-OHDA lesions of the entorhinal cortex made more errors and took nearly twice as long to reacquire criterion performance relative to control animals during post-surgical retraining. However, once criterion performance was re-attained, the behavior of lesioned animals was indistinguishable from controls on a version of the task involving longer delay periods. These findings point to multiple mechanisms through which exposure to different concentrations of dopamine may modulate sensory and mnemonic processing by modulating synaptic transmission within the lateral entorhinal cortex.

Divisions:Concordia University > Faculty of Arts and Science > Psychology
Item Type:Thesis (PhD)
Authors:Caruana, Douglas A
Pagination:xiii, 245 leaves : ill. ; 29 cm.
Institution:Concordia University
Degree Name:Ph. D.
Program:Psychology
Date:2008
Thesis Supervisor(s):Chapman, Andrew
ID Code:975605
Deposited By: Concordia University Library
Deposited On:22 Jan 2013 16:11
Last Modified:18 Jan 2018 17:40
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