Neurotransmitters are secreted by neurons and relay messages to target cells on a subsecond time scale. This proposal is directed at real-time monitoring of a specific neurotransmitter, dopamine (DA), in the brain of behaving rats. The sensing technology employs fast-scan cyclic voltammetry at carbon-fiber electrodes. DA is our target because it is a central player in the brain 'reward'system. It precise role is unclear because, until recent developments in our laboratory, a real-time view of all neurotransmitters was unavailable. The goal of the experiments described in this proposal is to investigate its role in behavior by directly observing its concentration fluctuations in distinct subregions within the brain, particularly the nucleus accumbens (NA), in awake rats executing behavioral tasks such as intracranial self-stimulation (ICS). During ICS, animals depress a lever to deliver an electrical stimulation to select brain pathways, a behavior that directly activates the brain reward circuitry. As with all reward-based behaviors, the events occur on a subsecond time scale, requiring high speed measurements for their observation. Simultaneously, we will be developing new analytical procedures that will further the information obtained during these behaviors. These experiments will clarify the neurochemical responses that underlie multiple reward based behaviors such as feeding, sexual activities, and drug abuse.
The specific aims for the project period are to develop new technology (Aims 1 and 4) and investigate the neurochemistry during behavior (Aims 2 and 3). They are: 1. To employ multiple electrodes to simultaneously probe different subregions of the brain during behavior and to develop methods to reduce the impact of the background current. 2. To investigate the origin of DA concentration transients. These dynamic features of DA neurotransmission have only been recognized recently. Transients occur spontaneously and are particularly notable in response to cues that predict reward availability. 3. To investigate the specific role of DA during ICS. This intriguing behavior short circuits normal behaviors and allows the the circuitry involved in reward to be directly investigated. 4. To develop and use new sensors for NO and pH for use in behaving animals. Both targets have dynamic concentration fluctuations in regions of the brain that use DA. Their detection will enable a more complete view of the chemical changes associated with reward.
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|Dankoski, Elyse C; Carroll, Susan; Wightman, Robert Mark (2016) Acute selective serotonin reuptake inhibitors regulate the dorsal raphe nucleus causing amplification of terminal serotonin release. J Neurochem 136:1131-1141|
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|Kirkpatrick, D C; Walton, L R; Edwards, M A et al. (2016) Quantitative analysis of iontophoretic drug delivery from micropipettes. Analyst 141:1930-8|
|Fox, Megan E; Bucher, Elizabeth S; Johnson, Justin A et al. (2016) Medullary Norepinephrine Projections Release Norepinephrine into the Contralateral Bed Nucleus of the Stria Terminalis. ACS Chem Neurosci 7:1681-1689|
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