Inhibiting Mesolimbic Dopamine Neurons Reduces the Initiation and Maintenance of Instrumental Responding. (21st February 2018)

• Record Type: Journal Article
• Authors: Fischbach-Weiss, Sarah; Reese, Rebecca M.; Janak, Patricia H.
• Is Part Of: Neuroscience. Volume 372(2018)
• Page Start: 306
• Page End: 315
• Publication Date: 2018-02-21
• Subjects: BSA bovine serum albumin -- FSCV fast scan cyclic voltammetry -- IRI inter-response intervals -- NAc nucleus accumbens -- NDS normal donkey serum -- PR progressive ratio -- RPE reward prediction error -- TH tyrosine hydroxylase; motivation -- instrumental learning -- optogenetics -- ventral tegmental area -- progressive ratio; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2017.12.003
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Is midbrain dopamine neuron activity required for responding on fixed ratio and progressive ratio tasks in mice? Optogenetic inhibition of dopamine neurons decreases the likelihood of initiation a response bout. Optogenetic inhibition of dopamine neurons after bout initiation decreases the likelihood of bout completion. Mice counteract depressant effects of dopamine inhibition during no-inhibition periods to maintain overall reward levels. Abstract: Mesolimbic dopamine perturbations modulate performance of reward-seeking behavior, with tasks requiring high effort being especially vulnerable to disruption of dopamine signaling. Previous work primarily investigated long-term perturbations such as receptor antagonism and dopamine depletion, which constrain the ability to assess dopamine contributions to effort expenditure in isolation from other behavior events, such as reward consumption. Also unclear is if dopamine is required for both initiation and maintenance when a sequence of multiple instrumental responses is required. Here we used optogenetic inhibition of midbrain TH+ neurons to probe the role of dopamine neuron activity during instrumental responding for reward by varying the time epoch of neural inhibition relative to the time of response initiation. Within a fixed-ratio procedure, requiring eight nosepoke responses per reinforcer delivery, or a progressive ratio (PR) procedure, in which within-session response requirements increased exponentially, inhibiting dopamine neurons while mice were engaged in response bouts decreased the probability of continued responding. If inhibition occurred during each attempted bout, the effect was to decrease total responses, and thus amount of rewards earned, over a session. In contrast, if inhibition was applied only during some bouts, mice increased the number of bouts initiated to earn control levels of reward. Inhibiting dopamine neurons while mice were not responding decreased the probability of initiating an instrumental response but had no effect on the amount of effort exerted over the entire session. We conclude that midbrain dopamine signaling promotes initiation of instrumental responding and maintains motivation to continue ongoing bouts of effortful responses.