Daniel Hill Abstracts

Daniel Hill

Ph.D. Candidate

Physiological Sciences GIDP

Society for Neuroscience Annual Meeting

San Diego, California

November 3-7, 2018

Dopaminergic signaling is known for its role in reward valuation, reinforcement learning, and memory. Dysregulation of dopamine signaling is also implicated in neuropathological conditions such as depression, schizophrenia, movement disorders, and addiction. Dopamine is released from ventral tegmental area (VTA) neurons and acts on dopamine receptors in the nucleus accumbens (NAc) to modulate cortical input. Dopaminergic terminals in the NAc are thought to release dopamine in response to large population-level burst activity in the VTA. However, the exact relationship between VTA cell activity and NAc dopamine release has not been established due to technological limitations that have prevented simultaneous measurement of both dopamine release and single-unit activity. To address this, we collected simultaneous measurements of cell firing in the VTA and dopamine release in the NAc using a novel measurement tool developed in our laboratory that integrates extracellular electrophysiological recording with fast-scan cyclic voltammetry. To induce phasic dopamine release, anesthetized Sprague Dawley rats (n = 10, 3 – 4 months old, 1 – 1.5 % isoflurane) were injected with dopamine transporter inhibitor GBR-12909 (17.5 mg/kg, i.p.) and D2 receptor antagonist eticlopride (0.75 mg/kg, i.p.). Although we predicted that a large portion of recorded dopamine neurons would fire before the onset of transient dopamine release events, we found instead that only ~ 8 % of VTA dopamine neurons exhibited reliable peri-event responses before a dopamine transient release event. Additionally, transient dopamine release events were associated with small (< 1 Hz) increases in dopamine neuron activity. Neurons that did exhibit reliable responses to transient dopamine release events responded long before the onset of transient dopamine release (980 ± 403 ms SEM; n = 5 neurons). We also observed that the firing rate of putative GABAergic neurons in the neighboring ‘tail’ of the VTA (tVTA), a region thought to be the ‘master brake’ of the VTA, decreased as cell firing of both dopaminergic and non-dopaminergic neurons in the VTA increased. Taken together these data suggest that NAc dopamine release is encoded by sparse signals from VTA dopamine neurons that are under tight control by inhibitory neurons of the tVTA.

Abstract for Lay Audience

Dopamine is a neurotransmitter (chemical messenger) in the brain that is involved in movement, learning, and memory. When dopamine signaling goes awry, neurological disorders such as Parkinson’s, schizophrenia, and addiction may result. Therefore, it is critical to understand how dopamine release is mediated in the brain. The largest group of cells that produce dopamine can be found in the midbrain a structure in the deepest portion of the brain called the brain stem. When these cells increase their activity, dopamine is thought to be released downstream in brain regions responsible for facilitating movement and decision making. Though this has been shown indirectly, dopamine release and dopamine-cell activity have never been measured simultaneously due to technological challenges. We developed a novel recording system capable of measuring dopamine and cell activity in order to better understand how the activity of dopamine cells gives rise to dopamine release. Interestingly, preliminary results suggest that dopamine cell activity and dopamine release are not as correlated as previously thought. This might mean that there are other mechanisms mediating dopamine release than just cell activity alone. These results suggest that we may need to reassess how we view the role of dopamine cell activity in neurological diseases associated with changes in dopamine sig