Biology subjects

Goodpaster, C. M.

Publications and source records attributed to Goodpaster, C. M..

4 recordsLinked to original sources

bioRxiv2025

Early adversity potentiates prefrontal - amygdala communication through CRH+ glutamatergic neurons

Early life adversity (ELA) has lasting impacts on emotion circuit function1. Exposure to early maltreatment, neglect, or household instability is associated with enduring alterations in threat evaluation and response, hallmarks of mood and anxiety disorders2-4. These alterations often emerge during adolescence and are characterized by excessive avoidance that limits engagement in rewarding experiences5,6. However, the neurodevelopmental mechanisms linking ELA to increased threat responses remain unclear. We identified a stress-sensitive medial prefrontal cortex (mPFC)-basolateral amygdala pathway that co-expresses corticotropin-releasing hormone (CRH) and glutamate. We find that ELA strengthens this pathway and increases threat avoidance behavior during adolescence. Optogenetic inhibition and developmental CRH knockdown in this pathway both rescue ELA-induced elevations in adolescent avoidance, whereas broadly reducing mPFC CRH expression in typically reared mice mimics ELA phenotypes. The same manipulations produced no behavioral effects in adults. Together, our findings indicate that cell type-specific CRH signaling regulates developmental circuit plasticity, biasing emotional circuit function and potentially contributing to psychiatric vulnerability.

neuroscience↗

bioRxiv2023

Developmentally distinct architectures in top-down circuits

The medial prefrontal cortex (mPFC) plays a key role in learning, mood and decision making, including in how individuals respond to threats1-6. mPFC undergoes a uniquely protracted development, with changes in synapse density, cortical thickness, long-range connectivity, and neuronal encoding properties continuing into early adulthood7-21. Models suggest that before adulthood, the slow-developing mPFC cannot adequately regulate activity in faster-developing subcortical centers22,23. They propose that during development, the enhanced influence of subcortical systems underlies distinctive behavioural strategies of juveniles and adolescents and that increasing mPFC control over subcortical structures eventually allows adult behaviours to emerge. Yet it has remained unclear how a progressive strengthening of top-down control can lead to nonlinear changes in behaviour as individuals mature24,25. To address this discrepancy, here we monitored and manipulated activity in the developing brain as animals responded to threats, establishing direct causal links between frontolimbic circuit activity and the behavioural strategies of juvenile, adolescent and adult mice. Rather than a linear strengthening of mPFC synaptic connectivity progressively regulating behaviour, we uncovered multiple developmental switches in the behavioural roles of mPFC circuits targeting the basolateral amygdala (BLA) and nucleus accumbens (NAc). We show these changes are accompanied by axonal pruning coinciding with functional strengthening of synaptic connectivity in the mPFC-BLA and mPFC-NAc pathways, which mature at different rates. Our results reveal how developing mPFC circuits pass through distinct architectures that may make them optimally adapted to the demands of age-specific challenges.

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bioRxiv2022

Dopamine projections to the basolateral amygdala drive the encoding of identity-specific reward memories

To make adaptive decisions, we build an internal model of the associative relationships in an environment and use it to make predictions and inferences about specific available outcomes. Detailed, identity-specific cue-reward memories are a core feature of such cognitive maps. Here we used fiber photometry, cell-type and pathway-specific optogenetic manipulation, Pavlovian cue-reward conditioning, and decision-making tests in male and female rats, to reveal that ventral tegmental area dopamine (VTADA) projections to the basolateral amygdala (BLA) drive the encoding of identity-specific cue-reward memories. Dopamine is released in the BLA during cue-reward pairing and VTADA[->]BLA activity is necessary and sufficient to link the identifying features of a reward to a predictive cue, but does not assign general incentive properties to the cue or mediate reinforcement. These data reveal a dopaminergic pathway for the learning that supports adaptive decision making and help explain how VTADA neurons achieve their emerging multifaceted role in learning.

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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↗