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Author ︱ Liu Mengyu edited ︱ Wang Sizhen's physiological state changes, the same individual will have different responses to the same stimulus
.
There is a very common phenomenon in the social interaction activities of human beings and even the entire mammalian world: the same female individual will have different psychological feelings when encountering social objects of the opposite sex, or receiving sexual contact of the opposite sex— "Like" or "reject", thereby showing the exact opposite behavioral response - "sexual receptivity" or "aggression"
.
One of the key factors in regulating "erotic desire and anger" is the current physiological state of the woman, such as breastfeeding
.
For non-lactating women, male social partners are potential mates
.
In this physiological state, female individuals show a higher degree of receptivity to male sexual contact
.
However, when the female becomes a mother and enters lactation, the same male loses her sexual attraction and becomes a threat to the survival of her offspring
.
Therefore, nursing mothers will reject male sexual contact, and even attack and bite them
.
What's more interesting is that this extreme change in "love and anger" is reversible
.
When lactating mothers are weaned, their aggression subsides and they show high sexual receptivity towards male subjects
.
This phenomenon is evolutionarily conserved and has been documented in a variety of mammals[1]
.
The physiological state of breastfeeding allows the same female to completely overturn her perception of the same social stimuli, resulting in completely opposite social responses
.
However, the neural mechanism of this phenomenon is still unclear
.
On January 3, 2022, David J.
Anderson's laboratory at the California Institute of Technology published an article titled "Make war not love: The neural substrate underlying a state-dependent switch in female social behavior" in Neuron.
The group level revealed the neural mechanism of female social behaviors with changes in lactation status
.
In this study, Mengyu Liu (first author) and others found that in the ventrolateral subdivision of ventromedial hypothalamus (VMHvl), two distinct neuronal subtypes specifically regulate female eroticism and anger - sexual acceptance and aggression
.
These two types of neurons can flexibly change the relative intensity of responses to male odor signals according to the individual's lactation state, enabling female individuals to make appropriate behavioral decisions
.
1.
Female sexual behavior and aggressive behavior activate different neuronal subtypes.
A small area of the hypothalamus, VMHvl, in female mice, shows a higher response to male social objects in both sexual receptive and aggressive states [2] ]
.
But whether the same neuronal population responded in the two different contexts was not known (Fig.
1B)
.
Therefore, first, the authors applied neuronal activity-dependent single-cell sequencing technology (activity dependent-scRNAseq) to explore the types of neurons that are activated in sexually receptive and aggressive states, respectively
.
The results showed that two distinct neuronal subtypes (alpha, beta) were activated in non-lactating females, which displayed high sexual receptivity, and lactating females, which displayed high aggression (Fig.
1EH)
.
Figure 1 Female sexual behavior and aggressive behavior activate different neuron subtypes (Source: Liu M.
et al.
, Neuron, 2021) Second, alpha and beta neurons control female sexual receptivity and aggression, respectively.
In order to further explore this The regulatory role of two neuronal subtypes on sexual and aggressive behavior.
The authors specifically express light-sensitive proteins on the surface of alpha and beta neurons in female mice, inhibit or activate specific subtypes during social interaction, and observe the effect on behavior.
influence
.
The results showed that specifically activating alpha neurons greatly improved sexual receptivity in female mice
.
In the activated state, non-estrus females, who were avoiding and screaming to male sexual contact, gradually slowed down and calmed down, and changed their body posture (lordosis) to cater to the male's courtship behavior and induce mating (intromission, ejaculation).
Conversely, the specific activation of beta neurons will immediately trigger a fierce attack on social objects in females, and can even overcome the limitations of the physiological state of lactation, in docile and non-aggressive conditions elicited aggressive biting in non-lactating females (Figure 3)
.
Figure 2 Activation of alpha neurons increases female sexual receptivity and inhibits aggressive behavior (Source: Liu M.
et al.
, Neuron, 2021) More interestingly, these two types of neurons have positive effects on their corresponding social behaviors.
In addition to the control effect, it has a curb effect on another social behavior
.
Activation of the alpha neuron subtype associated with sexual desire can make the aggressive mother immediately stop fighting; while activation of the aggression-related neuron subtype beta can cause female mice enjoying mating to immediately show rejection of male subjects , turn to attack, bite (Figure 2 HK, Figure 3 OP)
.
Figure 3 Activation of beta neurons triggers female aggressive behavior and inhibits sexual behavior (Source: Liu M.
et al.
, Neuron, 2021) 3.
In social interaction, alpha and beta neurons encode male sexual contact and self-aggression, respectively How do these two types of neurons dynamically change their responses during a complete social interaction? Next, the authors applied calcium imaging (photometry) to observe changes in the activity of alpha and beta neuronal populations during social interactions
.
The results showed that, in females, sex-related alpha neurons had strong selective responses to heterosexual odor information, such as urine, but very low responses to same-sex or abiotic odors (Fig.
4)
.
In addition to odor information, alpha neurons have a high-intensity response to heterosexual contact (mount) (Fig.
5)
.
Figure 4 Selective responses of female alpha neurons to male odor information (Source: Liu M.
et al.
, Neuron, 2021) Figure 5 Female alpha neurons responding to male sexual contact (Source: Liu M.
et al.
, Neuron, 2021) Correspondingly, aggressive behavior-related beta neurons remain low-responsive during sexual intercourse, or non-aggressive socializing
.
However, in high-aggressive mothers, both the smell of social objects (sniff) or aggressive behavior were accompanied by high-intensity responses from beta neurons (Fig.
6)
.
Figure 6 Female beta neurons encode aggression (Source: Liu M.
et al.
, Neuron, 2021) 4.
Aggression-related beta neurons show a lactation-dependent response to social object information The authors further explored female Social behavior in different lactation states depends on which neuronal activity changes
.
To this end, the authors tracked the responses of alpha and beta neurons of the same female to the same male odorant signals during virgin, lactation, and post-weaning physiological states
.
The results showed that the response of aggression-related beta neurons to male signals exhibited reversible lactation-state-dependent changes: low responses in virginity and post-weaning, but high responses during lactation
.
Sexual behavior-related alpha neurons did not exhibit lactation-state-dependent changes in responses (Fig.
7)
.
Figure 7 The response of female beta neurons to male information varies with lactation (Source: Liu M.
et al.
, Neuron, 2021) Conclusion and discussion, inspiration and prospect A neuron subtype that specifically regulates female "erotic desire and anger" -- sexual receptivity and aggression
.
These two types of neurons flexibly adjust the relative response strength to male signals dynamically according to the individual's breastfeeding state, thereby changing the female individual's emotional and behavioral responses to social objects
.
Sexual behavior and aggressive behavior are both innate social behaviors, which animals possess without learning, and play a key role in the survival of species
.
Therefore, the neural circuits that control this behavior are evolutionarily conserved and fixed
.
However, on the other hand, the variable physiological state still requires the organism to have the flexibility to adjust the stereotyped behavior
.
In this study, at the level of cellular subtypes, we have found the hub that coordinates this contradiction - beta neurons
.
However, how the physiological state modulates the activity of beta neurons was not addressed in this study
.
Changes in physiological state are accompanied by changes in hormones or other neuromodulators
.
Beta neurons express multiple hormone receptors, such as the estrogen receptor (Esr1)
.
What factors are involved in the regulation? And how does it work? This covers possible changes in the activatability of beta neurons themselves, as well as other cell-type signaling upstream of the circuit
.
The neural substrate revealed in this study provides a platform and foundation for research in this direction
.
Link to the original text: https://doi.
org/10.
1016/j.
neuron.
2021.
12.
002 Liu Mengyu (left), David J.
Anderson (right) (photo courtesy of Anderson's lab) Academician of the National Academy of Sciences from Caltech, HHMI Researcher, Professor David J.
Anderson, the corresponding author of the article
.
PhD student Mengyu Liu is the first author of the study
.
Selected Previous Articles【1】Nat Neurosci︱Jingjing Liu et al reveal the regulatory effect of hypothalamic melanin-clustering hormone on the activity of the hippocampal-dorsolateral septal loop【2】J Neurosci︱Merlin Lab reveals the mechanism of producing sharp ripples and spatial working memory Necessary signaling pathway: NRG1/ErbB4【3】Autophagy︱Li Xiaojiang’s team found new progress in the clearance of TDP-43 cytoplasmic aggregation by SQSTM1 in a non-human primate model【4】Nat Neurosci︱Cao Peng’s lab found that pain is a function of species Important functions in the struggle for survival between humans 【5】Neurosci Bull︱Tong Li’s research group revealed that dopaminergic neurons in the VTA-PrL neural pathway play a role in promoting wakefulness in rats under general anesthesia with sevoflurane 【6】Nat Aging︱Alzhai New discovery of mutated disease: a regulatory mechanism of bone marrow-derived macrophages independent of TREM2 pathway【7】Sci Transl Med︱New evidence of delayed onset of monoaminergic antidepressants: hippocampal cAMP regulates HCN channel function and thus affects small Mouse behavior and memory【8】Nat Methods︱Peng Hanchuan’s research group developed cross-modal brain registration technology, which provides important support for brain atlas construction and single-cell accurate whole-brain mapping research【9】Nat Commun︱Astrocytes inhibit non- Infiltration of peripheral macrophages in human primate cerebral ischemic injury【10】Cereb Cortex | Commonly used experimental paradigms for control and executive function [2] Symposium on Single-Cell Sequencing and Spatial Transcriptomics Data Analysis Lectures/Conferences/Seminars [1] Neuroscience Bulletin Online Academic Symposium Takes you to parse the nervous system development references (swipe up and down to view ) [1] OJ Bosch, “Maternal aggression in rodents: Brain oxytocin and vasopressin mediate pup defence,” Philosophical Transactions of the Royal Society B: Biological Sciences, vol.
368, no.
1631.
05-Jan-2013.
[2] K.
Hashikawa et al.
,“Esr1+ cells in the ventromedial hypothalamus control female aggression,” Nat.
Neurosci.
, vol.
20, no.
11, pp.
1580–1590, 2017.
Edition by Wang Sizhen
.
There is a very common phenomenon in the social interaction activities of human beings and even the entire mammalian world: the same female individual will have different psychological feelings when encountering social objects of the opposite sex, or receiving sexual contact of the opposite sex— "Like" or "reject", thereby showing the exact opposite behavioral response - "sexual receptivity" or "aggression"
.
One of the key factors in regulating "erotic desire and anger" is the current physiological state of the woman, such as breastfeeding
.
For non-lactating women, male social partners are potential mates
.
In this physiological state, female individuals show a higher degree of receptivity to male sexual contact
.
However, when the female becomes a mother and enters lactation, the same male loses her sexual attraction and becomes a threat to the survival of her offspring
.
Therefore, nursing mothers will reject male sexual contact, and even attack and bite them
.
What's more interesting is that this extreme change in "love and anger" is reversible
.
When lactating mothers are weaned, their aggression subsides and they show high sexual receptivity towards male subjects
.
This phenomenon is evolutionarily conserved and has been documented in a variety of mammals[1]
.
The physiological state of breastfeeding allows the same female to completely overturn her perception of the same social stimuli, resulting in completely opposite social responses
.
However, the neural mechanism of this phenomenon is still unclear
.
On January 3, 2022, David J.
Anderson's laboratory at the California Institute of Technology published an article titled "Make war not love: The neural substrate underlying a state-dependent switch in female social behavior" in Neuron.
The group level revealed the neural mechanism of female social behaviors with changes in lactation status
.
In this study, Mengyu Liu (first author) and others found that in the ventrolateral subdivision of ventromedial hypothalamus (VMHvl), two distinct neuronal subtypes specifically regulate female eroticism and anger - sexual acceptance and aggression
.
These two types of neurons can flexibly change the relative intensity of responses to male odor signals according to the individual's lactation state, enabling female individuals to make appropriate behavioral decisions
.
1.
Female sexual behavior and aggressive behavior activate different neuronal subtypes.
A small area of the hypothalamus, VMHvl, in female mice, shows a higher response to male social objects in both sexual receptive and aggressive states [2] ]
.
But whether the same neuronal population responded in the two different contexts was not known (Fig.
1B)
.
Therefore, first, the authors applied neuronal activity-dependent single-cell sequencing technology (activity dependent-scRNAseq) to explore the types of neurons that are activated in sexually receptive and aggressive states, respectively
.
The results showed that two distinct neuronal subtypes (alpha, beta) were activated in non-lactating females, which displayed high sexual receptivity, and lactating females, which displayed high aggression (Fig.
1EH)
.
Figure 1 Female sexual behavior and aggressive behavior activate different neuron subtypes (Source: Liu M.
et al.
, Neuron, 2021) Second, alpha and beta neurons control female sexual receptivity and aggression, respectively.
In order to further explore this The regulatory role of two neuronal subtypes on sexual and aggressive behavior.
The authors specifically express light-sensitive proteins on the surface of alpha and beta neurons in female mice, inhibit or activate specific subtypes during social interaction, and observe the effect on behavior.
influence
.
The results showed that specifically activating alpha neurons greatly improved sexual receptivity in female mice
.
In the activated state, non-estrus females, who were avoiding and screaming to male sexual contact, gradually slowed down and calmed down, and changed their body posture (lordosis) to cater to the male's courtship behavior and induce mating (intromission, ejaculation).
Conversely, the specific activation of beta neurons will immediately trigger a fierce attack on social objects in females, and can even overcome the limitations of the physiological state of lactation, in docile and non-aggressive conditions elicited aggressive biting in non-lactating females (Figure 3)
.
Figure 2 Activation of alpha neurons increases female sexual receptivity and inhibits aggressive behavior (Source: Liu M.
et al.
, Neuron, 2021) More interestingly, these two types of neurons have positive effects on their corresponding social behaviors.
In addition to the control effect, it has a curb effect on another social behavior
.
Activation of the alpha neuron subtype associated with sexual desire can make the aggressive mother immediately stop fighting; while activation of the aggression-related neuron subtype beta can cause female mice enjoying mating to immediately show rejection of male subjects , turn to attack, bite (Figure 2 HK, Figure 3 OP)
.
Figure 3 Activation of beta neurons triggers female aggressive behavior and inhibits sexual behavior (Source: Liu M.
et al.
, Neuron, 2021) 3.
In social interaction, alpha and beta neurons encode male sexual contact and self-aggression, respectively How do these two types of neurons dynamically change their responses during a complete social interaction? Next, the authors applied calcium imaging (photometry) to observe changes in the activity of alpha and beta neuronal populations during social interactions
.
The results showed that, in females, sex-related alpha neurons had strong selective responses to heterosexual odor information, such as urine, but very low responses to same-sex or abiotic odors (Fig.
4)
.
In addition to odor information, alpha neurons have a high-intensity response to heterosexual contact (mount) (Fig.
5)
.
Figure 4 Selective responses of female alpha neurons to male odor information (Source: Liu M.
et al.
, Neuron, 2021) Figure 5 Female alpha neurons responding to male sexual contact (Source: Liu M.
et al.
, Neuron, 2021) Correspondingly, aggressive behavior-related beta neurons remain low-responsive during sexual intercourse, or non-aggressive socializing
.
However, in high-aggressive mothers, both the smell of social objects (sniff) or aggressive behavior were accompanied by high-intensity responses from beta neurons (Fig.
6)
.
Figure 6 Female beta neurons encode aggression (Source: Liu M.
et al.
, Neuron, 2021) 4.
Aggression-related beta neurons show a lactation-dependent response to social object information The authors further explored female Social behavior in different lactation states depends on which neuronal activity changes
.
To this end, the authors tracked the responses of alpha and beta neurons of the same female to the same male odorant signals during virgin, lactation, and post-weaning physiological states
.
The results showed that the response of aggression-related beta neurons to male signals exhibited reversible lactation-state-dependent changes: low responses in virginity and post-weaning, but high responses during lactation
.
Sexual behavior-related alpha neurons did not exhibit lactation-state-dependent changes in responses (Fig.
7)
.
Figure 7 The response of female beta neurons to male information varies with lactation (Source: Liu M.
et al.
, Neuron, 2021) Conclusion and discussion, inspiration and prospect A neuron subtype that specifically regulates female "erotic desire and anger" -- sexual receptivity and aggression
.
These two types of neurons flexibly adjust the relative response strength to male signals dynamically according to the individual's breastfeeding state, thereby changing the female individual's emotional and behavioral responses to social objects
.
Sexual behavior and aggressive behavior are both innate social behaviors, which animals possess without learning, and play a key role in the survival of species
.
Therefore, the neural circuits that control this behavior are evolutionarily conserved and fixed
.
However, on the other hand, the variable physiological state still requires the organism to have the flexibility to adjust the stereotyped behavior
.
In this study, at the level of cellular subtypes, we have found the hub that coordinates this contradiction - beta neurons
.
However, how the physiological state modulates the activity of beta neurons was not addressed in this study
.
Changes in physiological state are accompanied by changes in hormones or other neuromodulators
.
Beta neurons express multiple hormone receptors, such as the estrogen receptor (Esr1)
.
What factors are involved in the regulation? And how does it work? This covers possible changes in the activatability of beta neurons themselves, as well as other cell-type signaling upstream of the circuit
.
The neural substrate revealed in this study provides a platform and foundation for research in this direction
.
Link to the original text: https://doi.
org/10.
1016/j.
neuron.
2021.
12.
002 Liu Mengyu (left), David J.
Anderson (right) (photo courtesy of Anderson's lab) Academician of the National Academy of Sciences from Caltech, HHMI Researcher, Professor David J.
Anderson, the corresponding author of the article
.
PhD student Mengyu Liu is the first author of the study
.
Selected Previous Articles【1】Nat Neurosci︱Jingjing Liu et al reveal the regulatory effect of hypothalamic melanin-clustering hormone on the activity of the hippocampal-dorsolateral septal loop【2】J Neurosci︱Merlin Lab reveals the mechanism of producing sharp ripples and spatial working memory Necessary signaling pathway: NRG1/ErbB4【3】Autophagy︱Li Xiaojiang’s team found new progress in the clearance of TDP-43 cytoplasmic aggregation by SQSTM1 in a non-human primate model【4】Nat Neurosci︱Cao Peng’s lab found that pain is a function of species Important functions in the struggle for survival between humans 【5】Neurosci Bull︱Tong Li’s research group revealed that dopaminergic neurons in the VTA-PrL neural pathway play a role in promoting wakefulness in rats under general anesthesia with sevoflurane 【6】Nat Aging︱Alzhai New discovery of mutated disease: a regulatory mechanism of bone marrow-derived macrophages independent of TREM2 pathway【7】Sci Transl Med︱New evidence of delayed onset of monoaminergic antidepressants: hippocampal cAMP regulates HCN channel function and thus affects small Mouse behavior and memory【8】Nat Methods︱Peng Hanchuan’s research group developed cross-modal brain registration technology, which provides important support for brain atlas construction and single-cell accurate whole-brain mapping research【9】Nat Commun︱Astrocytes inhibit non- Infiltration of peripheral macrophages in human primate cerebral ischemic injury【10】Cereb Cortex | Commonly used experimental paradigms for control and executive function [2] Symposium on Single-Cell Sequencing and Spatial Transcriptomics Data Analysis Lectures/Conferences/Seminars [1] Neuroscience Bulletin Online Academic Symposium Takes you to parse the nervous system development references (swipe up and down to view ) [1] OJ Bosch, “Maternal aggression in rodents: Brain oxytocin and vasopressin mediate pup defence,” Philosophical Transactions of the Royal Society B: Biological Sciences, vol.
368, no.
1631.
05-Jan-2013.
[2] K.
Hashikawa et al.
,“Esr1+ cells in the ventromedial hypothalamus control female aggression,” Nat.
Neurosci.
, vol.
20, no.
11, pp.
1580–1590, 2017.
Edition by Wang Sizhen
