Impairments in operant probabilistic reversal learning in BTBR T+tf/J male and female mice

Alvarez, Bryan D.; Morales, Cheyenne A.; Oliver, Brandon L.; Cavazos, Cassandra; Amodeo, Leslie R.; Amodeo, Dionisio A.

doi:10.1016/j.bbr.2022.114111

Cited by 2 publications

(1 citation statement)

References 26 publications

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“…However, it remains unclear how these effects translate to more conventional definitions of exploitatory and exploratory behavior, such as persisting in the pursuit and exploitation of a well-known option for acquiring resources versus the exploration of alternative options. To test if MRN neurons can also regulate explore/exploit choices in tasks in which mice act on previously gained knowledge of how to maximize short-term benefits, we trained food-restricted mice on a T-maze task 29,30 , in which a food reward was provided consistently only in one specific arm and not the other. In well-trained mice (>90% correct trials in two sequential sessions), the percentage of trials in which they enter the non-rewarded arm indicates their tendency to explore ( Fig.…”

Section: Main Textmentioning

confidence: 99%

A subcortical switchboard for exploratory, exploitatory, and disengaged states

Ahmadlou,

Shirazi,

Zhang

et al. 2023

Preprint

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To survive in evolving environments with uncertain resources, animals need to dynamically adapt their behavior and exhibit flexibility in choosing appropriate behavioral strategies, for example, to exploit familiar choices, to explore and acquire novel information, or to disengage altogether. Previous studies have mainly investigated how forebrain regions represent choice costs and values as well as optimal decision strategies during explore/exploit trade-offs. However, the neural mechanisms by which the brain implements alternative behavioral strategies such as exploiting, exploring or disengaging from the environment, remains poorly understood. Here we identify a neural hub critical for flexible switching between behavioral strategies, the median raphe nucleus (MRN). Using cell-type specific optogenetic manipulations, calcium fiber photometry and circuit tracing in mice performing diverse instinctive and learnt behavioral tasks, we found that the MRN’s main cell types, GABAergic, glutamatergic (VGluT2-positive), and serotonergic neurons, have complementary functions and drive exploitation, exploration and disengagement, respectively. Suppression of MRN GABAergic neurons, for instance through inhibitory input from lateral hypothalamus which conveys strong positive valence to the MRN, leads to perseverance in current actions and goals, and thus promotes exploitatory behavior. In contrast, activation of MRN VGluT2+ neurons drives exploratory behavior. Activity of serotonergic MRN neurons is necessary for general task engagement. Input from the lateral habenula conveying negative valence suppresses serotonergic MRN neurons, leading to disengagement. These findings establish the MRN as a central behavioral switchboard, uniquely positioned to flexibly control behavioral strategies. These circuits thus may also play an important role in the etiology and possible treatment of major mental pathologies such as depressive or obsessive-compulsive disorders.

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Section: Main Textmentioning

confidence: 99%

A subcortical switchboard for exploratory, exploitatory, and disengaged states

Ahmadlou,

Shirazi,

Zhang

et al. 2023

Preprint

View full text Add to dashboard Cite

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Dynamic Foraging Behavior Performance Is Not Affected byScn2aHaploinsufficiency

Schamiloglu,

Wu,

Zhou

et al. 2023

eNeuro

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Dysfunction in the geneSCN2A, which encodes the voltage-gated sodium channel Nav1.2, is strongly associated with neurodevelopmental disorders including autism spectrum disorder and intellectual disability (ASD/ID). This dysfunction typically manifests in these disorders as a haploinsufficiency, where loss of one copy of a gene cannot be compensated for by the other allele.Scn2ahaploinsufficiency affects a range of cells and circuits across the brain, including associative neocortical circuits that are important for cognitive flexibility and decision-making behaviors. Here, we tested whetherScn2ahaploinsufficiency has any effect on a dynamic foraging task that engages such circuits.Scn2a+/−mice and wild-type (WT) littermates were trained on a choice behavior where the probability of reward between two options varied dynamically across trials and where the location of the high reward underwent uncued reversals. Despite impairments inScn2a-related neuronal excitability, we found that both male and femaleScn2a+/−mice performed these tasks as well as wild-type littermates, with no behavioral difference across genotypes in learning or performance parameters. Varying the number of trials between reversals or probabilities of receiving reward did not result in an observable behavioral difference, either. These data suggest that, despite heterozygous loss ofScn2a, mice can perform relatively complex foraging tasks that make use of higher-order neuronal circuits.

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Impairments in operant probabilistic reversal learning in BTBR T+tf/J male and female mice

Cited by 2 publications

References 26 publications

A subcortical switchboard for exploratory, exploitatory, and disengaged states

A subcortical switchboard for exploratory, exploitatory, and disengaged states

Dynamic Foraging Behavior Performance Is Not Affected byScn2aHaploinsufficiency

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