Dopamine neurons in the ventral tegmental area (VTA) are strongly implicated in cognitive and affective processing as well as in psychiatric disorders including schizophrenia, ADHD and substance abuse disorders. In human studies, dopamine-related functions are routinely assessed using functional magnetic resonance imaging (fMRI) measures of blood oxygenation-level dependent (BOLD) signals during the performance of dopamine-dependent tasks. There is, however, a critical void in our knowledge about if and how activation of VTA dopamine neurons specifically influences regional or global fMRI signals. Here we used optogenetics in Th::Cre rats to selectively stimulate VTA dopamine neurons while simultaneously measuring global hemodynamic changes using BOLD and cerebral blood volume-weighted (CBVw) fMRI. Phasic activation of VTA dopamine neurons increased BOLD and CBVw fMRI signals in VTA-innervated limbic regions, including the ventral striatum (nucleus accumbens). Surprisingly, basal ganglia regions that receive sparse or no VTA dopaminergic innervation, including the dorsal striatum and the globus pallidus, were also activated. In fact, the most prominent fMRI signal increase in the forebrain was observed in the dorsal striatum that is not traditionally associated with VTA dopamine neurotransmission. These data establish causation between phasic activation of VTA dopamine neurons and global fMRI signals. They further suggest that mesolimbic and non-limbic basal ganglia dopamine circuits are functionally connected and, thus, provide a potential novel framework for understanding dopamine-dependent functions and interpreting data obtained from human fMRI studies.

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Acetylcholine (ACh) is associated with the modulation of brain activity linked to arousal, attention, and emotional valence. We performed dual-color mesoscopic imaging of ACh and calcium across the neocortex of awake mice to investigate the spatiotemporal dynamics of cholinergic signaling and their relationship to cortical output. We find distinct movement-defined behavioral states are represented in spatially heterogeneous cholinergic networks that are differentially coupled to fluctuations in local circuit activity.

Highlights d Dopamine activation controls prefrontal cortex (PFC) ensemble activity and oscillations d Concurrent influence on PFC individual unit activity is weak and heterogeneous d Effects of dopamine are governed by behavioral state and phasic activity pattern d Spatiotemporal diversity of dopamine's effects may enable complex PFC computations