Blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) is a non-invasive imaging technique that infers the presence of increased brain activity from localized increases in oxygenated hemoglobin. Interpreting BOLD data largely depends on the assumption that neuronal firing and increased blood flow directly correlate across the brain in a process known as neurovascular coupling. However, the influence of vasoactive neurotransmitters on BOLD signals have been largely ignored in interpreting brain functionality, such that current interpretations are incomplete. This is especially crucial to understand in the striatum, a brain region heavily involved in reward prediction and drug addiction, where coupling is not conserved. The vasoactive neurotransmitter dopamine is abundant throughout the striatum, yet its modulatory role over striatal hemodynamics is poorly understood. This proposed work seeks to understand how dopamine and striatal neurons contribute to both positive and negative BOLD responses to direct brain stimulation. By using a cutting-edge suite of techniques, we will selectively stimulate dopamine neurons or striatal neurons with optogenetics and systematically eliminate neuronal or neurotransmitter receptor components to investigate their contribution to the hemodynamic response. In response to a stimulus, fast-scan cyclic voltammetry will detect local dopamine and oxygen changes at an implantable microelectrode, and fMRI will be used simultaneously to monitor oxygen changes across the brain. Pharmacology and chemogenetics will be used to selectively activate or inhibit receptors and cell types. These experiments will expand our ability to interpret fMRI data accurately by establishing and quantifying both neuronal and neurotransmitter contributions to the striatal hemodynamic response.
Dopamine is a neurotransmitter known to modulate blood vessel diameters and play a role in neurological pathologies such as Parkinson's disease, attention deficit disorders, and drug addiction. Functional magnetic resonance imaging (fMRI) studies have found that blood flow in the striatum, a brain region rich in dopamine terminals, responds to different stimulations in ways that are inconsistent with the predictable blood flow changes in other brain regions. This proposed research will determine how neurons, dopamine, and other neurotransmitters factor into evoked hemodynamic responses in the striatum, which is crucial to accurately interpret fMRI signals.