Dopamine neurons do not constitute an obligatory stage in the final common path for the evaluation and pursuit of brain stimulation reward

Abstract

The neurobiological study of reward was launched by the discovery of intracranial selfstimulation (ICSS). Subsequent investigation of this phenomenon provided the initial link between reward-seeking behavior and dopaminergic neurotransmission. We re-evaluated this relationship by psychophysical, pharmacological, optogenetic, and computational means. In rats working for direct, optical activation of midbrain dopamine neurons, we varied the strength and opportunity cost of the stimulation and measured time allocation, the proportion of trial time devoted to reward pursuit. We found that the dependence of time allocation on the strength and cost of stimulation was similar formally to that observed when electrical stimulation of the medial forebrain bundle served as the reward. When the stimulation is strong and cheap, the rats devote almost all their time to reward pursuit; time allocation falls off as stimulation strength is decreased and/or its opportunity cost is increased. A 3D plot of time allocation versus stimulation strength and cost produces a surface resembling the corner of a plateau (the "reward mountain"). We show that dopamine-transporter blockade shifts the mountain along both the strength and cost axes in rats working for optical activation of midbrain dopamine neurons. In contrast, the same drug shifted the mountain uniquely along the opportunity-cost axis when rats worked for electrical MFB stimulation in a prior study. Dopamine neurons are an obligatory stage in the dominant model of ICSS, which positions them at a key nexus in the final common path for reward seeking. This model fails to provide a cogent account for the differential effect of dopamine transporter blockade on the reward mountain. Instead, we propose that midbrain dopamine neurons and neurons with non-dopaminergic, MFB axons constitute parallel limbs of brain-reward circuitry that ultimately converge on the final-common path for the evaluation and pursuit of rewards.

Optogenetic stimulation of ventral tegmental area dopaminergic neurons in a female rodent model of depression: The effect of different stimulation patterns

“…Some authors propose that a key mechanism of mfb DBS is the antidromic activation of the highly excitable myelinated glutamatergic inputs into the midbrain DA neurons. The dopaminergic projections in turn modulate numerous up‐stream antidepressant effects in the NAC and PFC (Schlaepfer et al., 2014) (Trujillo‐Pisanty et al., 2020). Furthermore, it is not known how optogenetic stimulation of the DA system impacts on the noradrenergic system, although it is recognized that the cross‐talk between the transmitters in stress regulation is important (Isingrini et al., 2016).…”

Introducing the PLOS ONE Collection on the neuroscience of reward and decision making

“…A major challenge for the field-as evidenced by the diversity of research contained within this Collection of papers-is understanding how the findings from individual studies can be integrated to develop a cohesive framework for elucidating how the brain processes rewards and makes decisions. For example, how might the parallel limbs of brain-reward circuitry proposed by Trujillo-Pisanty et al [31] modulate changes in prefrontal activity that occur in response to surprise and uncertainty, as reported by Kluger et al [18] and Shapiro and Grafton [22]? Could risk for developing habitual behaviors be the result of enhanced activity of striatal patches (e.g., striosomes; [33]) that, subsequently, alters the connectivity of the globus pallidus externus in response to psychotropic drugs as was observed by Fede et al [37]?…”

“…They found that dopamine manipulations can significantly alter the opportunity cost, but not the strength, of reward-seeking responding reinforced by LH-MFB stimulation. In the present study, Trujillo-Pisanty et al [31] examined the effects of dopamine transporter blockade on reward-seeking responding reinforced by optogenetic stimulation of ventral tegmental dopamine neurons, while varying the reward strength and opportunity cost of the stimulation. The selective dopamine transporter blocker GBR-12909 affected both strength and cost measures of dopamine neuron stimulation.…”

The trade-off between pulse duration and power in optical excitation of midbrain dopamine neurons approximates Bloch’s law

“…The counter model implies that beyond the outputs of the activated midbrain dopamine neurons, there is a neural signal, (dubbed "reward intensity") whose amplitude in response to a pulse train of a given duration is a monotonic function of the aggregate firing rate 23 . According to the single-operant matching law 6,[24][25][26] , time allocation is a monotonic function of reward intensity and hence of the aggregate firing rate as well. Thus, during a pulse-duration sweep, time allocation is a monotonic function of pulse duration.…”