Arvanitogiannis, A. | Search bioRxiv

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.

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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

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