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Modulation of the mesocorticolimbic dopamine system by the central nucleus of the amygdala : electrophysiological and behavioural analyses

University of British Columbia

Accumulating evidence implicates the amygdala as the main brain region underlying anxiety and, in a parallel stream of research, suggests that dopamine (DA) may be a key neuromodulator of experimental anxiety. However, little is currently known about how the primary output area, the central nucleus, of the amygdala (CeA) and the mesocorticolimbic D A system interact. Chapter 2 sought to directly assess the role of the CeA in neurophysiological alterations occurring at the D A cell-body region of the ventral tegmental area (VTA). The C eA was either activated via pharmacological antagonism of G A B A A receptors or inactivated via pharmacological agonism of G A B A A / G A B A B receptors. Subsequently, in vivo electrophysiological measures were used to examine the modulation of V T A D A neuron (i) population activity, (ii) firing rate, and (iii) bursting. CeA activation resulted in a significant increase in the population activity and bursting of V T A D A neurons. Conversely, inactivation of the CeA resulted in a significant reduction in the population activity of these cells. These are the first electrophysiological data to demonstrate that the CeA elicits differential regulation of distinct physiological parameters of V T A D A neurons. To complement these findings, Chapter 3 describes experiments that investigated the effects of C eA inactivation, in a manner similar to that used in Chapter 2, utilizing a behavioural approach. This series of experiments employed a mesocortical DA-dependent conflict paradigm that simultaneously incorporates appetitive (Reward) and aversive (Conflict) components. CeA inactivation resulted in a significant reduction of responding during the Reward components and a significant increase in lever-pressing during the Conflict period of the conflict test (Experiment 1) and its variant, the extinction of conflict test (Experiment 2). The data from Chapter 3 suggest that the CeA plays dissociable roles in mediating motivational responding under appetitive conditions and suppressing responding following exposure to aversive, conflict-inducing, stimuli. Collectively, the results from Chapter 2 and Chapter 3 offer corroborating evidence from electrophysiological and behavioural perspectives for the role of the CeA in modulating the mesocorticolimbic D A system. Ultimately, the systems approach implemented in the current study may offer novel insight into the neurophysiological mechanisms by which one area of the amygdala mediates experimental anxiety.

Thesis/Dissertation

application/pdf

2009-03-06

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/5626

Neuroscience

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/