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Shizgal, P.

Publications and source records attributed to Shizgal, P..

7 recordsLinked to original sources
bioRxiv2025

Optical activation of midbrain dopamine neurons: do high and low stimulation frequencies produce functionally different effects?

Millard et al. propose1 that 20- and 50-Hz stimulation of optically excitable, midbrain dopamine neurons triggers functionally distinct effects: The "physiological" firing elicited by a 20-Hz train mimics a reward-prediction error (RPE) whereas the "supra-physiological" firing induced by a 50-Hz train creates "a sensory event that acts as a reward in its own right." Only the 50-Hz trains supported vigorous responding in the face of elevated response costs and sufficed to produce reward-specific Pavlovian-Instrumental Transfer (PIT). Nonetheless, the 20-Hz trains did produce unblocking. Here, we propose a more parsimonious account of these findings that is consistent with the results of prior experiments on operant responding for rewarding optical2-4 or electrical5-9 stimulation and with a new theory10,11 of the role of dopamine signaling in associative conditioning: 1) The effects of the 20- and 50-Hz trains differ quantitatively rather than qualitatively. They are mapped onto a single dimension, reward intensity, which reflects the aggregate release of dopamine in the critical terminal field(s). 2) The non-linear dependence of operant responding on both the aggregate dopamine release and the response cost3 can explain why responding for the 20- and 50 Hz trains diverged as response cost grew and predicts that this divergence can be eliminated by increasing the number of dopamine neurons stimulated. 3) Terminal-field dopamine concentration provides no information about pulse frequency per se. 4) Operant responding, PIT, and unblocking all depend on reward intensity, but the form and parameters of this dependence can differ, thus generating the observed contrasts in the impact of the 20- and 50-Hz trains. 5) The tested range of experimental conditions is too narrow to specify what constitutes "physiological" firing.

neuroscience↗
bioRxiv2022

A novel method for measuring the priming effect of rewarding brain stimulation

Receipt of an intense reward boosts motivation to work for more of that reward. This phenomenon is called the priming effect of rewards. Using a novel measurement method, we show that the priming effect of rewarding electrical brain stimulation depends on the cost, as well as on the strength, of the anticipated reward. Previous research on the priming effect of electrical brain stimulation utilized a runway paradigm in which running speed serves as the measure of motivation. In the present study, the measure of motivation was the vigor with which rats executed a two-lever response chain, in a standard operant-conditioning chamber, to earn rewarding electrical stimulation of the lateral hypothalamus. In a second experiment, we introduced a modification that entails self-administered priming stimulation and alternating blocks of primed and unprimed trials. Reliable, consistent priming effects of substantial magnitude were obtained in the modified paradigm, which is closely analogous to the runway paradigm. In a third experiment, the modified paradigm served to assess the dependence of the priming effect on dopamine D2-like receptors. The priming effect proved resilient to the effect of eticlopride, a selective D2-like receptor antagonist. These results are discussed within the framework of a new model of brain reward circuitry in which non-dopaminergic medial forebrain bundle fibers and dopamine axons provide parallel inputs to the final common paths for reward and incentive motivation.

neuroscience↗
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↗
bioRxiv2021

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

BackgroundOptogenetic experiments reveal functional roles of specific neurons. However, such inferences have been restricted by widespread adoption of a fixed set of stimulation parameters. Broader exploration of the parameter space can deepen insight into the mapping between selective neural activity and behavior. In this way, characteristics of the activated neurons, such as temporal integration, can be inferred. ObjectiveTo determine whether an equal-energy principle accounts for the interaction of pulse duration and optical power in optogenetic excitation. MethodsSix male TH::Cre rats worked for optogenetic (ChannelRhodopsin-2) stimulation of Ventral Tegmental Area dopamine neurons. We used a within-subject design to describe the trade-off between pulse duration and optical power in determining reward seeking. Parameters were customized for each subject on the basis of behavioral effectiveness. ResultsWithin a useful range of powers (~12.6-31.6 mW) the product of optical power and pulse duration required to produce a given level of reward seeking was roughly constant. Such reciprocity is consistent with Blochs law, which posits an equal-energy principle of temporal summation over short durations in human vision. The trade-off between pulse duration and power broke down at higher powers. ConclusionsOptical power can be substituted for pulse duration to scale the region of neuronal excitation in behavioral optogenetic experiments. Power and duration can be adjusted reciprocally for brief durations and lower powers. The findings demonstrate the utility of within-subject and trade-off designs in optogenetics and of parameter adjustment based on functional endpoints instead of physical properties of the stimulation. HighlightsO_LIWe provide behaviorally derived intensity-duration curves for ChannelRhodopsin-2. C_LIO_LIDuration trades off almost perfectly with power within useful ranges. C_LIO_LIThis trade-off breaks down at high optical powers. C_LIO_LIPulse duration and optical power scale the area of neuronal excitation equivalently. C_LIO_LIBehaviorally derived trade-offs can reveal optogenetic excitation mechanisms. C_LI

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↗
bioRxiv2018

Forgetful inference in a sophisticated world model

Humans and other animals are able to discover underlying statistical structure in their environments and exploit it to achieve efficient and effective performance. However, such structure is often difficult to learn and use because it is obscure, involving long-range temporal dependencies. Here, we analysed behavioural data from an extended experiment with rats, showing that the subjects learned the underlying statistical structure, albeit suffering at times from immediate inferential imperfections as to their current state within it. We accounted for their behaviour using a Hidden Markov Model, in which recent observations are integrated with the recollections of an imperfect memory. We found that over the course of training, subjects came to track their progress through the task more accurately, a change that our model largely attributed to decreased forgetting. This learning to remember decreased reliance on recent observations, which may be misleading, in favour of a longer-term memory.\n\nAuthor summaryHumans and other animals possess the remarkable ability to find and exploit patterns and structures in their experience of a complex and varied world. However, such structures are often temporally extended and latent or hidden, being only partially correlated with immediate observations of the world. This makes it essential to integrate current and historical information, and creates a challenging statistical and computational problem.\n\nHere, we examine the behaviour of rats facing a version of this challenge posed by a brain-stimulation reward task. We find that subjects learned the general structure of the task, but struggled when immediate observations were misleading. We captured this behaviour with a model in which subjects integrated evidence from their observations together with a memory whose imperfections accounted for their errors.\n\nThe subjects performance improved markedly over successive sessions, allowing them to overcome misleading observations. According to the model, this arose from a process of learning to remember in which subjects became better at employing more reliable past observations to determine the hidden state of the world.

neuroscience↗