Reorganization of theta phase-locking in the orbitofrontal cortex drives cocaine choice under the influence

Karine Guillem,Serge H Ahmed

doi:10.1038/s41598-020-64962-w

Abstract

Cortical theta oscillations of neuronal activity are a fundamental mechanism driving goal-directed behavior. We previously identified in the rat orbitofrontal cortex (OFC) a neuronal correlate of individual preferences between cocaine use and an alternative nondrug reward (i.e. saccharin). Whether theta oscillations are also associated with choice behavior between a drug and a nondrug reward remains unknown. Here we investigated the temporal structure between single unit activity and theta band oscillations (4–12 Hz) in the OFC of rats choosing between cocaine and saccharin. First, we found that the relative amplitude of theta oscillations is associated with subjective value and preference between two rewards. Second, OFC phase-locked neurons fired on opposite phase of the theta oscillation during saccharin and cocaine rewards, suggesting the existence of two separable neuronal assemblies. Finally, the pharmacological influence of cocaine at the moment of choice altered both theta band power and theta phase-locking in the OFC. That is, this drug influence shifted spike-phase relative to theta cycle and decreased the synchronization of OFC neurons relative to the theta oscillation. Overall, this study indicates that the reorganization of theta phase-locking under the influence of cocaine biases OFC neuronal assemblies in favor of cocaine choice and at the expense of a normally preferred alternative, a neuronal change that may contribute to drug preference in cocaine addiction.

Highlights

Cortical theta oscillations of neuronal activity are a fundamental mechanism driving goal-directed behavior
We found that drug and nondrug rewards are selectively encoded by two non-overlapping populations of orbitofrontal cortex (OFC) neurons, and that OFC spiking activity reflect the relative preference between the two types of options[11,12]
In our original study[11], we reported OFC neuronal spiking activity in rats choosing between a drug and a nondrug reward

Summary

Introduction

Cortical theta oscillations of neuronal activity are a fundamental mechanism driving goal-directed behavior. That is, this drug influence shifted spike-phase relative to theta cycle and decreased the synchronization of OFC neurons relative to the theta oscillation. OFC neurons encode incentive value and the relative preference when choosing between two rewards of the same kind (e.g., two different amounts of food)[4,5,6,7,8,9,10] We recently extended these findings to choice between drugs of abuse (i.e., cocaine) and nondrug alternative rewards (i.e., water sweetened with saccharin)[11,12]. We compared OFC theta oscillatory activity and spike field phase-looking when choices were made drug free versus under the influence of cocaine

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Results

Conclusion