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An electrophysiological investigation of the extrinsic modulation of ventral pallidum neurons by dopamine and serotonin

Clark, Martin (2018) An electrophysiological investigation of the extrinsic modulation of ventral pallidum neurons by dopamine and serotonin. PhD thesis, University of Sheffield.

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The ventral pallidum (VP) is a key output structure of the basal ganglia and has multiple connections with cortical and limbic regions. The VP is modulated by extrinsic neurotransmitters, including dopamine and serotonin, but the cellular mechanisms underlying this modulation are only partially understood. This thesis describes an in vitro electrophysiological investigation of such extrinsic modulation employing extracellular multi electrode recordings of the VP and pharmacological manipulations. Our data provide novel information on how dopamine modulates VP neurons acting both pre- and post-synaptically. Presynaptic excitatory effects of dopamine are mediated by D1-like and D2-like receptors, through effects on glutamate release and subsequently ionotropic and metabotropic glutamate receptor activation. Postsynaptic, direct effects are mediated by D2-like receptors and induce decreases in firing frequency within the VP. Our data identifies two populations of neurons in the VP, which can be consistently separated by their spike half-width profile and their responses to D2-like receptor agonists. With regard to serotonin, both excitatory and inhibitory responses to its application were observed in the VP. Our data suggests that excitatory effects of Serotonin (5HT) are presynaptic, while the inhibitory responses to 5HT are postsynaptic, direct effects. Our data also suggest that 5HT1a, 5HT5A and 5HT7 receptors are responsible for increases in firing frequency to 5HT application and 5-HT2c receptors are likely candidates for the decrease in firing frequency to 5HT application in the VP. We also investigated the effects of electric activation of NAc inputs to the VP. Our data are consistent with the literature, showing that NAc inputs inhibit VP neurons. Overall, these results cast light on the cellular mechanism by which dopamine and serotonin modulate VP neurons and have important implications for our understanding of the role the VP plays in reward processing and related dysfunctions.

Item Type: Thesis (PhD)
Academic Units: The University of Sheffield > Faculty of Science (Sheffield)
The University of Sheffield > Faculty of Science (Sheffield) > Psychology (Sheffield)
Identification Number/EthosID: uk.bl.ethos.762562
Depositing User: Mr Martin Clark
Date Deposited: 21 Dec 2018 11:01
Last Modified: 25 Sep 2019 20:05
URI: http://etheses.whiterose.ac.uk/id/eprint/22438

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