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.

A Novel Assay Allowing Drug Self-Administration, Extinction, and Reinstatement Testing in Head-Restrained Mice.

Multiphoton microscopy is one of several new technologies providing unprecedented insight into the activity dynamics and function of neural circuits. Unfortunately, some of these technologies require experimentation in head-restrained animals, limiting the behavioral repertoire that can be integrated and studied. This issue is especially evident in drug addiction research, as no laboratories have coupled multiphoton microscopy with simultaneous intravenous drug self-administration, a behavioral paradigm that has predictive validity for treatment outcomes and abuse liability.

Relative salience signaling within a thalamo-orbitofrontal circuit governs learning rate.

Learning to predict rewards is essential for the sustained fitness of animals. Contemporary views suggest that such learning is driven by a reward prediction error (RPE)-the difference between received and predicted rewards. The magnitude of learning induced by an RPE is proportional to the product of the RPE and a learning rate.

Dissociable mesolimbic dopamine circuits control responding triggered by alcohol-predictive discrete cues and contexts.

Context can influence reactions to environmental cues and this elemental process has implications for substance use disorder. Using an animal model, we show that an alcohol-associated context elevates entry into a fluid port triggered by a conditioned stimulus (CS) that predicted alcohol (CS-triggered alcohol-seeking). This effect persists across multiple sessions and, after it diminishes in extinction, the alcohol context retains the capacity to augment reinstatement.

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

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.

Paraventricular Thalamus Projection Neurons Integrate Cortical and Hypothalamic Signals for Cue-Reward Processing.

The paraventricular thalamus (PVT) is an interface for brain reward circuits, with input signals arising from structures, such as prefrontal cortex and hypothalamus, that are broadcast to downstream limbic targets. However, the precise synaptic connectivity, activity, and function of PVT circuitry for reward processing are unclear. Here, using in vivo two-photon calcium imaging, we find that PVT neurons projecting to the nucleus accumbens (PVT-NAc) develop inhibitory responses to reward-predictive cues coding for both cue-reward associative information and behavior.

The Effects of Electrical and Optical Stimulation of Midbrain Dopaminergic Neurons on Rat 50-kHz Ultrasonic Vocalizations.

Rationale: Adult rats emit ultrasonic vocalizations (USVs) at around 50-kHz; these commonly occur in contexts that putatively engender positive affect. While several reports indicate that dopaminergic (DAergic) transmission plays a role in the emission of 50-kHz calls, the pharmacological evidence is mixed. Different modes of dopamine (DA) release (i.

Robust optical fiber patch-cords for in vivo optogenetic experiments in rats.

In vivo optogenetic experiments commonly employ long lengths of optical fiber to connect the light source (commonly a laser) to the optical fiber implants in the brain. Commercially available patch cords are expensive and break easily. Researchers have developed methods to build these cables in house for in vivo experiments with rodents [1-4].

Psychophysical inference of frequency-following fidelity in the neural substrate for brain stimulation reward.

The rewarding effect of electrical brain stimulation has been studied extensively for 60 years, yet the identity of the underlying neural circuitry remains unknown. Previous experiments have characterized the directly stimulated ("first-stage") neurons implicated in self-stimulation of the medial forebrain bundle. Their properties are consistent with those of fine, myelinated axons, at least some of which project rostro-caudally.

A new view of the effect of dopamine receptor antagonism on operant performance for rewarding brain stimulation in the rat.

Rationale: Previous studies of neuroleptic challenges to intracranial self-stimulation (ICSS) employed two-dimensional (2D) measurements (curve shifts). Results so obtained are ambiguous with regard to the stage of neural processing at which the drug produces its performance-altering effect. We substituted a three-dimensional (3D) method that measures reward-seeking as a function of both the strength and cost of reward.

Role of dopamine tone in the pursuit of brain stimulation reward.

Dopaminergic neurons contribute to intracranial self-stimulation (ICSS) and other reward-seeking behaviors, but it is not yet known where dopaminergic neurons intervene in the neural circuitry underlying reward pursuit or which psychological processes are involved. In rats working for electrical stimulation of the medial forebrain bundle, we assessed the effect of GBR-12909 (1-[2-[bis(4-fluorophenyl)-methoxy]ethyl]-4-[3- phenylpropyl]piperazine), a specific blocker of the dopamine transporter. Operant performance was measured as a function of the strength and cost of electrical stimulation.

Cannabinoid receptor blockade reduces the opportunity cost at which rats maintain operant performance for rewarding brain stimulation.

There is ample evidence that blockade of CB(1) receptors reduces reward seeking. However, the reported effects of CB(1) blockade on performance for rewarding electrical brain stimulation stand out as an exception. By applying a novel method for conceptualizing and measuring reward seeking, we show that AM-251, a CB(1) receptor antagonist, does indeed decrease performance for rewarding electrical stimulation of the medial forebrain bundle in rats.