Anatomical and computational models of the role of phasic dopamine signaling in intracranial self-stimulation: psychophysical and electrochemical tests
Dopamine (DA) neurotransmission is heavily implicated in electrical intracranial self-stimulation (eICSS), operant performance aimed at triggering stimulation of certain brain regions. To study the underpinnings of reward seeking, we combined ICSS with fast-scan cyclic voltammetry (FSCV), a means of monitoring stimulation-induced DA transients.
Chapter one examines the circuitry linking midbrain DA neurons to the non-DA neurons recruited at the tip of a medial forebrain bundle (MFB) eICSS electrode. We found that unilateral, electrical, MFB stimulation evoked bilateral DA transients and that DA activation occurred, in large part, through polysynaptic circuitry.
The series-circuit hypothesis is the focus of chapter two. On that view, the signal representing the intensity of the stimulation-induced rewarding effect must pass obligatorily through midbrain DA neurons. We found that the the DAergic projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) cannot serve as a unique link that relays the reward signal underlying eICSS of the MFB to later stages of the circuitry underlying reward seeking.
The last chapter addresses the dominant theory linking phasic DA signalling to learning. On that view, DA transients signal the discrepancy between expected and experienced rewards and adjust synaptic weights to update reward predictions and bias action selection. Several of our findings are difficult to reconcile with the DA-RPE hypothesis.
Recent technological advances have provided tools for studying the neural bases of reward seeking that are unprecedented in their power and number. It is important to extend this level of sophistication to our electrochemical and behavioural methods
