Biology subjects

Greenfield, V. Y.

Publications and source records attributed to Greenfield, V. Y..

4 recordsLinked to original sources

bioRxiv2021

The medial orbitofrontal cortex - basolateral amygdala circuit regulates the influence of reward cues on adaptive behavior and choice

Adaptive reward-related decision making requires accurate prospective consideration of the specific outcome of each option and its current desirability. Often this information must be inferred based on the presence of predictive environmental events. The basolateral amygdala (BLA) and medial orbitofrontal cortex (mOFC) are two key nodes in the circuitry supporting such outcome expectations, but very little is known about the function of direct connections between these regions. Here, in male rats, we first anatomically confirmed the existence of bidirectional, direct projections between the mOFC and BLA and found that BLA projections to mOFC are largely distinct from those to lateral OFC (lOFC). Next, using pathway-specific chemogenetic inhibition and the outcome-selective Pavlovian-to-instrumental transfer and devaluation tests, we interrogated the function of the bidirectional mOFC-BLA connections in reward-directed behavior. We found evidence that the mOFC[->]BLA pathway mediates the use of environmental cues to understand which specific reward is predicted, information needed to infer which action to choose, and how desirable that reward is to ensure adaptive responses to the cue. By contrast, the BLA[->]mOFC pathway is not needed to use the identity of an expected reward to guide choice, but does mediate adaptive responses to cues based on the current desirability of the reward they predict. These functions differ from those we previously identified for the lOFC-BLA circuit. Collectively, the data reveal the mOFC-BLA circuit as critical for the cue-dependent reward outcome expectations that influence adaptive behavior and decision making. SIGNIFICANCE STATEMENTTo make good decisions we evaluate how advantageous a particular course of action would be. This requires understanding what rewarding outcomes can be expected and how desirable they currently are. Such prospective considerations are critical for adaptive decision making but disrupted in many psychiatric diseases. Here we reveal that direct connections between the medial orbitofrontal cortex and basolateral amygdala mediate these functions. These findings are especially important in light of evidence of dysfunction in this circuit in substance use disorder and mental illnesses marked by poor decision making.

neuroscience↗

bioRxiv2021

A bidirectional corticoamygdala circuit for the encoding and retrieval of detailed reward memories

Adaptive reward-related decision making often requires accurate and detailed representation of potential available rewards. Environmental reward-predictive stimuli can facilitate these representations, allowing one to infer which specific rewards might be available and choose accordingly. This process relies on encoded relationships between the cues and the sensory-specific details of the reward they predict. Here we interrogated the function of the basolateral amygdala (BLA) and its interaction with the lateral orbitofrontal cortex (lOFC) in the ability to learn such stimulus-outcome associations and use these memories to guide decision making. Using optical recording and inhibition approaches, Pavlovian cue-reward conditioning, and the outcome-selective Pavlovian-to-instrumental transfer (PIT) test in male rats, we found that the BLA is robustly activated at the time of stimulus-outcome learning and that this activity is necessary for sensory-specific stimulus-outcome memories to be encoded, so they can subsequently influence reward choices. Direct input from the lOFC was found to support the BLA in this function. Based on prior work, activity in BLA projections back to the lOFC was known to support the use of stimulus-outcome memories to influence decision making. By multiplexing optogenetic and chemogenetic inhibition we performed a serial circuit disconnection and found that the lOFC[->]BLA and BLA[->]lOFC pathways form a functional circuit regulating the encoding (lOFC[->]BLA) and subsequent use (BLA[->]lOFC) of the stimulus-dependent, sensory-specific reward memories that are critical for adaptive, appetitive decision making.

neuroscience↗

bioRxiv2018

Distinct cortical-amygdala projections drive reward value encoding and retrieval

The value of an anticipated rewarding event is crucial information in the decision to engage in its pursuit. The networks responsible for encoding and retrieving this value are largely unknown. Using glutamate biosensors and pharmacological manipulations, we found that basolateral amygdala (BLA) glutamatergic activity tracks and mediates both the encoding and retrieval of the state-dependent incentive value of a palatable food. Projection-specific and bidirectional chemogenetic and optogenetic manipulations revealed the orbitofrontal cortex (OFC) supports the BLA in these processes. Critically, the function of ventrolateral (lOFC) and medial (mOFC) OFC[->]BLA projections was found to be doubly dissociable. Whereas activity in lOFC[->]BLA projections is necessary for and sufficient to drive encoding of a positive change in the value of a reward, mOFC[->]BLA projections are necessary and sufficient for retrieving this value from memory to guide its pursuit. These data reveal a new circuit for adaptive reward valuation and pursuit, indicate dissociability in the encoding and retrieval of reward memories, and provide insight into the dysfunction in these processes that characterizes myriad psychiatric diseases.

neuroscience↗

bioRxiv2017

Habits are negatively regulated by HDAC3 in the dorsal striatum

Optimal behavior results from a balance of control between two strategies, one cognitive/goal-directed and one habitual, which rely on the anatomically distinct dorsomedial (DMS) and dorsolateral (DLS) striatum, respectively. The transcriptional regulatory mechanisms required to learn and transition between these strategies are unknown. Here we identified a critical negative regulator of habit learning. Histone deacetylase (HDAC) inhibition following instrumental conditioning accelerated habitual control of behavior. HDAC3, a transcriptional repressor, was removed from the promoters of learning-related genes in the dorsal striatum as habits formed with overtraining and with post-training HDAC inhibition. Decreasing HDAC3 function in the DLS accelerated habit formation, while DLS HDAC3 overexpression prevented habit. HDAC3 activity in the DMS was also found to constrain habit formation. These results challenge the strict dissociation between DMS and DLS function in goal-directed v. habitual behavioral control and identify dorsal striatal HDAC3 as a critical molecular substrate of the transition to habit.

neuroscience↗