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Hall, C. D.

Publications and source records attributed to Hall, C. D..

3 recordsLinked to original sources

Nucleus accumbens dopamine release reflects Bayesian inference during instrumental learning

Dopamine release in the nucleus accumbens has been hypothesized to signal reward prediction error, the difference between observed and predicted reward, suggesting a biological implementation for reinforcement learning. Rigorous tests of this hypothesis require assumptions about how the brain maps sensory signals to reward predictions, yet this mapping is still poorly understood. In particular, the mapping is non-trivial when sensory signals provide ambiguous information about the hidden state of the environment. Previous work using classical conditioning tasks has suggested that reward predictions are generated conditional on probabilistic beliefs about the hidden state, such that dopamine implicitly reflects these beliefs. Here we test this hypothesis in the context of an instrumental task (a two-armed bandit), where the hidden state switches repeatedly. We measured choice behavior and recorded dLight signals reflecting dopamine release in the nucleus accumbens core. Model comparison among a wide set of cognitive models based on the behavioral data favored models that used Bayesian updating of probabilistic beliefs. These same models also quantitatively matched the dopamine measurements better than non-Bayesian alternatives. We conclude that probabilistic belief computation contributes to instrumental task performance in mice and is reflected in mesolimbic dopamine signaling.

animal behavior and cognition↗

Prepubertal ovariectomy alters dorsomedial striatum indirect pathway neuron excitability and explore/exploit balance in female mice

Decision-making circuits are modulated across life stages (e.g. juvenile, adolescent, or adult)--as well as on the shorter timescale of reproductive cycles in females--to meet changing environmental and physiological demands. Ovarian hormone signaling may contribute to this flexibility by regulating neural circuits involved in adaptive decision making. Here, we examined how prepubertal ovariectomy (pOVX) influences adult performance in an odor-guided multiple-choice reversal task. During reversal learning, pOVX females exhibited a distinct pattern of errors compared to sham-operated controls. To characterize decision strategies, we fit a reinforcement learning model to trial-by-trial behavior across both the initial Discrimination and Reversal phases. Sham females showed a significant increase in the inverse temperature parameter ({beta}) during Reversal, consistent with a shift towards a more exploitative choice policy favoring high-value options. By contrast, pOVX females failed to show a phase-dependent increase in {beta}, suggesting they continued to use a more exploratory strategy. To identify a neural correlate of this behavioral phenotype, we performed whole-cell patch clamp recordings within the dorsomedial striatum (DMS), a region implicated in regulating action selection and explore/exploit choice policy. Intrinsic excitability of dopamine receptor type 2-expressing (D2R) indirect pathway spiny projection neurons (iSPNs) was significantly higher in pOVX females compared to both sham-operated and unmanipulated controls. Finally, to test whether increased D2R(+) iSPN excitability could causally contribute to the exploratory reversal phenotype, we chemogenetically activated DMS D2R(+) neurons in intact female mice. This manipulation increased exploratory choice during reversal learning, recapitulating the pattern observed following pOVX. Together, these data suggest that pubertal status may influence how females adapt their decision strategy between Discrimination and Reversal phases, potentially through long-lasting modulation of DMS iSPN intrinsic excitability.

neuroscience↗

Sex and pubertal status influence dendritic spine density onto frontal cortiocostriatal projection neurons

In humans, nonhuman primates, and rodents, the frontal cortices exhibit grey matter thinning and dendritic spine pruning that extends late into adolescence. This protracted maturation is believed to support higher cognition but may also confer psychiatric vulnerability during adolescence. Currently, little is known about how different cell types in the frontal cortex mature or whether puberty plays a role. Here, we used mice to characterize the spatial topography and adolescent development of cross-corticostriatal (cSTR) neurons that project to the dorsomedial striatum (DMS). We found that apical spine density on cSTR neurons in the medial prefrontal cortex decreased significantly between late juvenile (P29) and young adult time points (P60), with females exhibiting higher spine density than males at both ages. Adult males castrated prior to puberty onset had higher spine density compared to sham controls. Adult females ovariectomized before puberty onset showed greater variance in spine density measures on cSTR cells compared to controls, but their mean spine density did not significantly differ from sham controls. Our findings reveal that these cSTR neurons, a subtype of the broader class of intratelencephalic-type neurons, exhibit significant sex differences and suggest that spine pruning on cSTR neurons is regulated by puberty in males.

neuroscience↗