Biology subjects

Solis, P.

Publications and source records attributed to Solis, P..

3 recordsLinked to original sources

bioRxiv2022

Does phasic dopamine release cause policy updates?

Phasic dopamine activity is believed to both encode reward-prediction errors (RPEs) and to cause the adaptations that these errors engender. If so, a rat working for optogenetic stimulation of dopamine neurons will repeatedly update its policy and/or action values, thus iteratively increasing its work rate. Here, we challenge this view by demonstrating stable, non-maximal work rates in the face of repeated optogenetic stimulation of midbrain dopamine neurons. Furthermore, we show that rats learn to discriminate between world states distinguished only by their history of dopamine activation. Comparison of these results to reinforcement learning simulations suggests that the induced dopamine transients acted more as rewards than RPEs. However, pursuit of dopaminergic stimulation drifted upwards over a time scale of days and weeks, despite its stability within trials. To reconcile the results with prior findings, we consider multiple roles for dopamine signaling.

neuroscience↗

bioRxiv2020

Sexually dimorphic influence of the circadian clock gene Bmal1 in the striatum on alcohol intake

The gene Bmal1 (brain and muscle Arnt-like 1) plays an obligatory role in the generation of circadian rhythms in the suprachiasmatic nucleus (SCN), the master circadian clock in mammals [1-5]. Notably, Bmal1 is widely expressed in mammalian brain [6], and perturbations in Bmal1 expression in select forebrain regions cause behavioral disturbances that are independent of the SCN, such as disturbances in sleep architecture, and in cognitive and affective behaviors [1, 7-15]. Interestingly, gene association studies in humans and in animals suggest that Bmal1 may influence the propensity to consume alcohol, and that polymorphisms in Bmal1 may confer risk for alcohol dependence and related disorders [16-20]. However, research has not yet provided evidence of a causal role of Bmal1 in the control of alcohol intake. We investigated voluntary alcohol consumption in conditional knockout mice that lack Bmal1 exclusively in the striatum, which is an important structure in the control of alcohol intake and preference [21-26]. Experiments were carried out in both male and female mice in order to account for the known sex differences in alcohol consumption [27-31] and in striatal functioning [32-36], as well as in the expression of clock genes and in the impact of circadian clocks on behavior [37-44]. We found that, in both males and females, selective deletion of Bmal1 from principal medium spiny neurons (MSNs) of the striatum significantly altered voluntary alcohol intake and preference. Strikingly, the effect of Bmal1 deletion was sexually dimorphic. Whereas in males, deletion of Bmal1 augmented alcohol intake and preference, in females, the same deletion suppressed alcohol intake and preference. Interestingly, striatal deletion of the clock gene Per2, which interacts with Bmal1 in the generation of circadian rhythms [4], and which has been shown to affect alcohol consumption in male mice [45], mimicked the effect of Bmal1 deletion, albeit only in males. These results show that Bmal1 in MSNs of the striatum exerts a sexually dimorphic influence on alcohol intake in mice, moderating intake in males, possibly via Per2, and promoting heightened intake in females, independently of Per2. We propose that a sexually dimorphic mechanism in the function of Bmal1 in the striatum contributes to sex differences in the propensity to consume alcohol in mice. Whether such mechanism contributes to sex differences in other striatum-dependent appetitive and consummatory behaviors remains to be investigated.

neuroscience↗

bioRxiv2019

The effect of dopamine transporter blockade on optical self-stimulation: behavioral and computational evidence for parallel processing in brain reward circuitry

The neurobiological study of reward was launched by the discovery of intracranial self-stimulation (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. Author summaryTo succeed in the struggle for survival and reproductive success, animals must make wise choices about which goals to pursue and how much to pay to attain them. How does the brain make such decisions and adjust behaviour accordingly? An animal model that has long served to address this question entails delivery of rewarding brain stimulation. When the probe is positioned appropriately in the brain, rats will work indefatigably to trigger such stimulation. Dopamine neurons play a crucial role in this phenomenon. The dominant model of the brain circuitry responsible for the reward-seeking behavior treats these cells as a gateway through which the reward-generating brain signals must pass. Here, we challenge this idea on the basis of an experiment in which the dopamine neurons were activated selectively and directly. Mathematical modeling of the results argues for a new view of the structure of brain reward circuitry. On this view, the pathway(s) in which the dopamine neurons are embedded is one of a set of parallel channels that process reward signals in the brain. To achieve a full understanding of how goals are evaluated, selected and pursued, the full set of channels must be identified and investigated.

neuroscience↗