Mengyu Liu

All Publications

• Encoding of female mating dynamics by a hypothalamic line attractor. Nature Liu, M., Nair, A., Coria, N., Linderman, S. W., Anderson, D. J. 2024

  Abstract

  Females exhibit complex, dynamic behaviors during mating with variable sexual receptivity depending on hormonal status1-4. However, how their brains encode the dynamics of mating and receptivity remains largely unknown. The ventromedial hypothalamus, ventro-lateral subdivision contains estrogen receptor type 1-positive neurons that control mating receptivity in female mice5,6. Unsupervised dynamical systems analysis of calcium imaging data from these neurons during mating uncovered a dimension with slow ramping activity, generating a line attractor in neural state space. Neural perturbations in behaving females demonstrated relaxation of population activity back into the attractor. During mating population activity integrated male cues to ramp up along this attractor, peaking just before ejaculation. Activity in the attractor dimension was positively correlated with the degree of receptivity. Longitudinal imaging revealed that attractor dynamics appear and disappear across the estrus cycle and are hormone-dependent. These observations suggest that a hypothalamic line attractor encodes a persistent, escalating state of female sexual arousal or drive during mating. They also demonstrate that attractors can be reversibly modulated by hormonal status, on a timescale of days.

  View details for DOI 10.1038/s41586-024-07916-w

  View details for PubMedID 39142338

• Make war not love: The neural substrate underlying a state-dependent switch in female social behavior. Neuron Liu, M., Kim, D. W., Zeng, H., Anderson, D. J. 2022; 110 (5): 841-856.e6

  Abstract

  Female mice exhibit opposing social behaviors toward males depending on their reproductive state: virgins display sexual receptivity (lordosis behavior), while lactating mothers attack. How a change in reproductive state produces a qualitative switch in behavioral response to the same conspecific stimulus is unknown. Using single-cell RNA-seq, we identify two distinct subtypes of estrogen receptor-1-positive neurons in the ventrolateral subdivision of the female ventromedial hypothalamus (VMHvl) and demonstrate that they causally control sexual receptivity and aggressiveness in virgins and lactating mothers, respectively. Between- and within-subject bulk-calcium recordings from each subtype reveal that aggression-specific cells acquire an increased responsiveness to social cues during the transition from virginity to maternity, while the responsiveness of the mating-specific population appears unchanged. These results demonstrate that reproductive-state-dependent changes in the relative activity of transcriptomically distinct neural subtypes can underlie categorical switches in behavior associated with physiological state changes.

  View details for DOI 10.1016/j.neuron.2021.12.002

  View details for PubMedID 34982958

  View details for PubMedCentralID PMC8897222

• The neural computation of affective internal states in the hypothalamus: A dynamical systems perspective. Neuron Nair, A., Vinograd, A., Liu, M., Mountoufaris, G., Linderman, S., Anderson, D. J. 2025; 113 (23): 3887-3907

  Abstract

  Internal affective states accompany evolutionarily ancient survival behaviors such as mating, aggression, and predator defense and may contribute to emotional feelings in humans. In this perspective, we introduce a dynamical system framework for thinking about such states. We synthesize evidence from recent studies suggesting that key state features, such as their intensity and duration, may be encoded by approximate line attractor manifolds in the hypothalamus. Evidence for these attractors arises from unsupervised data-driven dynamical system modeling of high-dimensional calcium imaging data from genetically identified cell populations in freely behaving mice. Dissection of the fit dynamical models and closed-loop modeling with experimental perturbations raise new questions regarding circuit- and cellular-level mechanisms of attractor implementation. These findings challenge prevailing views of hypothalamic behavioral control and afford a new avenue to study the emergence of slow state-encoding neural dynamics across scales, from single neurons to recurrent networks and neuromodulatory signaling.

  View details for DOI 10.1016/j.neuron.2025.11.003

  View details for PubMedID 41344293

• A line attractor maintains aggressiveness during feeding in "hangry" mice. bioRxiv : the preprint server for biology Kim, J., Nair, A., Coria, N., Huynh, S., Vinograd, A., Xu, J., Liu, M., Anderson, D. J. 2025

  Abstract

  Aggression evolved to protect resources such as food from competitors, but animals must balance fighting and feeding so that they facilitate rather than hinder re-establishment of energy homeostasis. How this balancing is computed is not well understood. We have approached this problem at the level of neural population-coding by examining the effect of progressive starvation on a hypothalamic line attractor that encodes an internal state of aggressiveness. Moderate fasting yielded "hangry" mice, decreasing attack latency and increasing attack frequency. In parallel, line attractor ramping rate and stability were increased, suggesting that hunger enhances aggressiveness by modifying neural dynamics. In contrast, prolonged starvation inhibited aggression and eliminated the line attractor. In satiated mice, titrated acute chemogenetic activation of arcuate AgRP neurons recapitulated the biphasic effects of progressive starvation, suggesting that a continuous increase in hunger exerts bi-directional influences at different intensities. When confronted with food and an intruder, hangry mice alternated between feeding and fighting. During eating, population neural activity moved out of the line attractor while activity in the attractor dimension remained unchanged. Following feeding, activity rapidly relaxed back into the attractor and aggression resumed. Thus, the line attractor may serve to keep hungry animals primed for aggression during intermittent feeding bouts.

  View details for DOI 10.1101/2025.10.16.682711

  View details for PubMedID 41279704

  View details for PubMedCentralID PMC12632901

• Distinct hypothalamic control of same- and opposite-sex mounting behaviour in mice. Nature Karigo, T., Kennedy, A., Yang, B., Liu, M., Tai, D., Wahle, I. A., Anderson, D. J. 2021; 589 (7841): 258-263

  Abstract

  Animal behaviours that are superficially similar can express different intents in different contexts, but how this flexibility is achieved at the level of neural circuits is not understood. For example, males of many species can exhibit mounting behaviour towards same- or opposite-sex conspecifics1, but it is unclear whether the intent and neural encoding of these behaviours are similar or different. Here we show that female- and male-directed mounting in male laboratory mice are distinguishable by the presence or absence of ultrasonic vocalizations (USVs)2-4, respectively. These and additional behavioural data suggest that most male-directed mounting is aggressive, although in rare cases it can be sexual. We investigated whether USV+ and USV- mounting use the same or distinct hypothalamic neural substrates. Micro-endoscopic imaging of neurons positive for oestrogen receptor 1 (ESR1) in either the medial preoptic area (MPOA) or the ventromedial hypothalamus, ventrolateral subdivision (VMHvl) revealed distinct patterns of neuronal activity during USV+ and USV- mounting, and the type of mounting could be decoded from population activity in either region. Intersectional optogenetic stimulation of MPOA neurons that express ESR1 and vesicular GABA transporter (VGAT) (MPOAESR1∩VGAT neurons) robustly promoted USV+ mounting, and converted male-directed attack to mounting with USVs. By contrast, stimulation of VMHvl neurons that express ESR1 (VMHvlESR1 neurons) promoted USV- mounting, and inhibited the USVs evoked by female urine. Terminal stimulation experiments suggest that these complementary inhibitory effects are mediated by reciprocal projections between the MPOA and VMHvl. Together, these data identify a hypothalamic subpopulation that is genetically enriched for neurons that causally induce a male reproductive behavioural state, and indicate that reproductive and aggressive states are represented by distinct population codes distributed between MPOAESR1 and VMHvlESR1 neurons, respectively. Thus, similar behaviours that express different internal states are encoded by distinct hypothalamic neuronal populations.

  View details for DOI 10.1038/s41586-020-2995-0

  View details for PubMedID 33268894

  View details for PubMedCentralID PMC7899581