Nature Neuroscience. Detailed interpretation, found that the regulation of "eating" neurons were also involved in the control of "fighting" behavior.

Habenular nucleus is an ancient brain structure, which is conservative in almost all vertebrate species. Br / > in mammals, it is composed of a pair of medial habenular nuclei (MHB) and the medial habenular nucleus (MHB).in fish and amphibians, the corresponding parts of mammalian MHB and LHB are dorsal habenular nucleus (DHB) and ventral habenular nucleus (VHb). Br / >, especially in the lateral habenular nucleus (LHB), as reflected by the rapid growth of research in the past decade.it has been reported to be involved in a variety of neurophysiological activities, such as drug addiction, reward aversion, schizophrenia, pain and depression.LHB nucleus is a "star brain area" in the field of neuroscience in recent years.aggressive behavior is a characteristic of many neuropsychiatric disorders (such as autism spectrum disorder, attention deficit hyperactivity disorder, personality disorder, etc.), which will have a variety of negative effects on patients, their families and the public.studies in humans and animals have shown that the reward circuit of the brain is related to aggression, and in individuals with aggressive behavior, the desire to dominate low social level targets is increasing.previous studies have suggested that LHB is a potential regulator of aggressive social behavior.LHB is mainly glutamatergic neurons. Whether there are GABAergic neurons in LHB has been controversial. A small number of neurons in LHBM express gad2 (glutamic acid decarboxylase 2) and GAT1 (GABA transporter 1), but whether they express VGAT (vascular GABA transporter) is controversial. Therefore, it is not clear whether these GABAergic neurons can function normally.in addition, the role of specific LHB input and LHB local microloop in aggressive behavior is still unknown.Scott J. Russo, from the Department of neuroscience of Nash family, Icahn Medical College, USA, published an article entitled orexin signaling in GABAergic lateral habenulaneurens modules aggressive behavior in male mice in nature neuroscience.this study confirmed that only a small number of neurons expressed gad2 (18%).the authors divided male CD1 mice into two groups: highly aggressive (AGG) and non aggressive (non aggressive, non aggressive). The mice were killed 30 minutes after the third day of behavior, and brain slices were taken for c-fos staining analysis. It was found that the Fos positive rate and VGLUT2 + Fos positive rate of AGG group were lower than those of non group, but gad2 + positive rate was higher than non group.identified the important role of LHB gad2 + neurons in aggressive behavior.the authors further recorded the neuronal activity through optical fiber and injected aav-flex-gcamp6 virus into the LHB of GAD2 CRE mice.it was found that the activity of gad2 + neurons increased when AGG mice began to bite C57 mice, and decreased when they stopped biting C57 mice and retreated.the opposite was observed in non mice.the authors changed the behavior paradigm to detect the difference of neuronal activity between AGG and non mice when the intruder C57 mice were present or not.it was found that when C57 mice were present, the peak activity of gad2 + neurons in AGG rats increased significantly on the third day, while that of non mice showed a downward trend.finally, the authors found that AGG mice preferred the box with paired C57 mice, and the peak activity of gad2 + neurons increased significantly when the mice were located in the paired box, while there was no significant change in non mice.through a series of behavioral experiments, the authors confirmed that the activity of gad2 + neurons in LHB was dynamic in real-time. When the attack occurred, the activity of gad2 + neurons increased, and after the attack stopped, the activity of gad2 + neurons decreased.then, the authors found that there were a large number of oxr2 (orexin receptor 2) in LHB gad2 + neurons. Through electrophysiological experiments, it was found that the discharge frequency of gad2 + neurons increased after administration of orexin-A, and returned to normal after removing orexin-A.by qPCR, we found that the expression of LHB oxr2 mRNA in AGG mice was significantly increased after the third day of invasion.confirmed that LHB oxr2 mediates the increase of gad2 + neuronal activity in aggressive behavior.finally, the authors found that activation of LH orexin + terminal activated gad2 + neurons in LHB brain area, inhibited VGLUT2 + neuron activity and decreased the activity of overall LHB brain area neurons through photogenetics and staining.the authors confirmed that there was a local inhibitory microloop in LHB. Furthermore, in the light activated behavioral experiment, it was found that light activated LH orexin + - LHB shortened the latency and increased the duration of aggression in AGG mice, and the score showed an increasing trend in conditional preference test.the authors confirmed that orexin neurons in the lateral hypothalamus (LH) activated LHB gad2 + and mediated aggressive behavior.in conclusion, this paper describes in detail that LH orexin neurons in male mice activate a small group of LHB gad2 neurons through oxr2, which promotes aggressive behavior and aggressive conditioned place preference among male mice.in addition, LHB gad2 neurons were inhibited, which inhibited the activity of LHB as a whole.these results suggest that the orexin system is important in regulating aggressive behavior between male mice and provide evidence for LHB local inhibition of microloop.inspirations and questions: 1. This paper challenges the currently accepted LHB microloop (i.e., pure excitability) model, and confirms the regulatory role of LHB gad2 as a new inhibitory neuron.clarified the role of specific LHB input and LHB local inhibition microloop in aggressive behavior, which was the first time confirmed.2. Do LHB gad2 neurons release neuropeptides or other neurotransmitters other than GABA? 3. It should be noted that we have not found any evidence that gad2 neurons stimulate excitatory currents in the major LHB neurons, but this does not exclude the possibility of the release of other information substances from these neurons.in fact, a recent single cell sequencing study of LHB neurons found that gad2 expressing cells may also express transcripts encoding precursor neuropeptides, such as pituitary adenylate cyclase activating polypeptide and enkephalin. future research should focus on the co expression of gad2 and these neuropeptide precursors. 4. Whether LHB gad2 neurons have extensive inhibitory regulation on LHB projection neurons, or whether there are projection specific connections. it is worth noting that the two main output downstream of LHB, namely DRN and VTA, have been involved in previous studies on aggressive behavior, but the role of these target brain regions in regulating aggressive motivation is still poorly understood. future research should try to map the internal and external targets of LHB gad2 neurons, which are important for regulating aggressive behavior. 5. What is the role of other inputs of LHB gad2 neurons in aggressive behavior? In addition to oxr2, LHB gad2 neurons have also been shown to express estrogen and antidiuretic hormone receptors, both of which have been involved in previous aggressive behavior. it is also possible that other areas of the brain project to LHB and participate in the regulation of aggressive behavior, such as prefrontal cortex and lateral septum, which directly target LHB gad2 neurons to regulate aggressive behavior, which should also be verified in future studies. In general, this paper is a pioneering study, which is a great reference for the research group focusing on LHB. reference: detailed explanation of the article, cell reading | Dr. Yang peiguo found that g3bp1 phase transition mediates the formation of ribonucleoprotein particles