Richard Lab

Where are motivation and value encoded in the brain?

Cues that have been paired with rewards like food and drugs can become incentive cues, which have the ability to induce motivational states like craving, and to invigorate reward-seeking behaviors. One area of the brain where neurons encode motivational vigor is in the ventral pallidum. Around 70% of ventral pallidum neurons increase their activity following a sound cue predicting the availability of sugar. Importantly, we can predict based on these increases in activity whether animals will make a reward seeking response, and how fast they will be to make this response. And when we inhibit these neurons during the cue animals are slower and less likely to seek out sugar. These results make the ventral pallidum a promising area of the brain to study encoding of incentive value. Going forward, I hope to address the following questions in the ventral pallidum, and in other parts of the brain that encode motivated behavior: 

  1. Do neurons that encode cue-elicited reward seeking actions ("operant responses") similar encode other types of reward-seeking behaviors?
  2. Do cue responses that encode motivational vigor also encode the value of expected reward, or are these dissociable?
  3. How do changes in physiological state (e.g. hunger or specific physiological need) impact encoding of reward-predictive cues?
 
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What are the neural and psychological building blocks that contribute to motivated behavior?

In order to encode the incentive motivational value of cues neurons must either a) receive direct inputs encoding this incentive value or b) integrate multiple type of information (such as cue value, physiological or affective state, and situational factors) to generate a unique incentive value signal. In the case of the ventral pallidum, representations of incentive value occur at a short latency and in a larger proportion of the population than would be consistent with direct inputs encoding incentive value, at least from the nucleus accumbens. Yet, ventral pallidum neurons reverse inputs from a diverse array of inputs implicated in reward learning and motivation, including the basolateral amygdala, prefrontal cortex and paraventricular nucleus of the thalamus, which may all contribute to some aspect of incentive signaling. We aim to reverse engineer neural signals encoding incentive motivation by addressing the following questions:

  1. How does activity in inputs to neural encoding incentive motivation change leading up to and following reward-predictive cues, and what is encoded by these changes in activity?

  2. What is the functional contribution of specific projections to cue-elicited reward seeking?

  3. What inputs are recruited by factors such as extinction learning, and changes in physiological state or context?

How do these circuits contribute to alcohol abuse and relapse?

Drug and alcohol abuse presents major and increasing costs to society, and is a major source of both preventable death and economic burden. Abuse of alcohol and other drugs has been suggested to alter multiple aspects of motivation and affect related processes. These changes include alterations in the motivational value of cues in the environment, exaggerated negative affect and anxiety, and disruption of top-down cognitive control. Addiction is particularly insidious because of the long-term risk for relapse, even after long periods of abstinence. Improvements in our long-term treatment of drug and alcohol addiction will require major advancements of our understanding of the underlying neural mechanisms. We aim to determine the critical changes in neural circuits that contribute to pathological motivation and affect in drug and alcohol abuse, focused on the following initial questions:

  1. Do neural circuits encoding motivated behavior contribute similarly to seeking of natural and drug rewards?
  2. How does stress impact neural encoding of motivation during relapse-like behavior, and does stress recruit novel circuits that are not involved in drug and alcohol seeking in the absence of acute stress?
  3. How does alcohol dependence alter the motivational value of alcohol cues, and does this require new learning?