Minakuchi, T. | bioRxiv Science

bioRxiv2025

An automated two-choice social operant task for probing moment-to-moment changes in social satiety

In naturalistic conditions, animals must routinely make ongoing self-motivated choices about whether to initiate interactions with same or opposite-sex partners and whether to re-initiate social contact when interactions have ended. However, it remains unclear what governs these choices, and whether they are motivated by drive states that exhibit signatures of moment-to-moment social satiety when these interactions have ended. Here, to explicitly test this at the behavioral level, we designed a novel fully-automated two-choice social operant paradigm where individuals can choose between same and opposite-sex social rewards and rewards are delivered for interaction with systematically varying durations. We trained cohorts of both sexes on this task and quantified the patterns of choices. We used choice latency as a metric to infer moment-to-moment satiety to test whether increased interaction duration leads to increased moment-to-moment satiety. We find that although both males and females have stable choice biases across sessions, with males showing consistent opposite sex biases, only males exhibit behavioral signatures of moment-to-moment social satiety and are sensitive to the duration of interaction. Using a simple normative model to capture patterns of social choice, we observe that behavior is better fit by a model that has a single evolving social drive and choice bias, rather than a model with multiple, independent drives for same and opposite-sex interactions. Together, our data reveal behavioral signatures of social satiety and offer new insights into the underlying homeostatic and motivational drives that govern social choices.

neuroscience↗

bioRxiv2022

Independent inhibitory control mechanisms for aggressive motivation and action

Social behaviors, like other motivated behaviors, frequently consist of a flexible motivated-seeking or approach phase followed by social action. Dysregulated social behavior may arise from changes to motivation, wherein individuals fail to enter a motivated seeking state, or may be in the execution of the social action itself. However, it is unclear how the brain generates and gates this flexible motivation-to-action sequence, and whether aggressive motivation and action are controlled by separate circuit mechanisms. Here, we record populations of neurons in the ventromedial hypothalamus ventrolateral area (VMHvl) of male mice at cellular resolution during "free" aggression and also during an aggression operant task, where the behaviors that precede attack are stereotyped. We find that this population encodes the temporal sequence of aggressive motivation to action and that the temporal selectivity of neurons is invariant to differences in motivated behavior. To test whether motivation and action could be independently regulated, we focused on two key inhibitory inputs to the VMHvl: a source of local inhibition (VMHvl shell) and the primary source of long-range inhibition (the medial preoptic area, MPO). While we find that the VMHvl receives broad monosynaptic inhibitory input from both inputs, optogenetic perturbation of these inputs during recording reveals temporal selectivity during aggressive motivation and action, suggesting specificity of function. Encoding models applied to population calcium recordings of these inhibitory inputs during naturalistic social interactions and during the social operant task further reveal that these inputs have different temporal dynamics during aggression: VMHvl shellvgat+ activity peaks at the start of aggressive interactions, while MPO-VMHvlvgat+ activity peaks at behaviorally aligned endpoints of aggressive interactions. Finally, using closed-loop optogenetic stimulation timed to specific phases of the aggression-operant task, we find a double-dissociation of the effects on aggressive motivation and action: activation of MPO-VMHvlvgat+, even briefly and temporally distant from the initiation of aggression, produces long-lasting motivational deficits, delaying the initiation of aggression and generating behaviors consistent with an unmotivated state. In contrast, activation of VMHvl shellvgat+ produces acute action-related deficits, causing an exit from an attack state. Fitting a Hidden Markov Model (HMM) to behavior further corroborates these findings by showing that MPO-VMHvlvgat+ stimulation prolongs a low motivation state and VMHvl shellvgat+ promotes exit from an attack state. Together, these data demonstrate how separable inhibitory circuits in the hypothalamus can independently gate the motivational and action phases of aggression through a single locus of control.

neuroscience↗