Risold, P. Y. & Swanson, L. W. Connections of the rat lateral septal complex. Brain Res. Rev. 24, 115–195 (1997).
Besnard, A. & Leroy, F. Top-down regulation of motivated behaviors via lateral septum sub-circuits. Mol. Psychiatry 27, 3119–3128 (2022).
Risold, P. Y. & Swanson, L. W. Chemoarchitecture of the rat lateral septal nucleus1Published on the World Wide Web on 2 June 1997.1. Brain Res. Rev. 24, 91–113 (1997).
Franklin, T. B., Saab, B. J. & Mansuy, I. M. Neural mechanisms of stress resilience and vulnerability. Neuron 75, 747–761 (2012).
Henckens, M. J. A. G., Deussing, J. M. & Chen, A. Region-specific roles of the corticotropin-releasing factor–urocortin system in stress. Nat. Rev. Neurosci. 17, 636–651 (2016).
Anthony, T. E. et al. Control of stress-induced persistent anxiety by an extra-amygdala septohypothalamic circuit. Cell 156, 522–536 (2014).
Hashimoto, M. et al. Lateral septum modulates cortical state to tune responsivity to threat stimuli. Cell Rep. 41, 111521 (2022).
Sheehan, T. P., Chambers, R. A. & Russell, D. S. Regulation of affect by the lateral septum: implications for neuropsychiatry. Brain Res. Rev. 46, 71–117 (2004).
Albert, D. J. & Chew, G. L. The septal forebrain and the inhibitory modulation of attack and defense in the rat. A review. Behav. Neur. Biol. 30, 357–388 (1980).
Wirtshafter, H. S. & Wilson, M. A. Lateral septum as a nexus for mood, motivation, and movement. Neurosci. Biobehav. Rev. 126, 544–559 (2021).
Dai, B. et al. Experience-dependent dopamine modulation of male aggression. Nature 639, 430–437 (2025).
Reyes, N. S. et al. Corticotropin-releasing hormone signaling from prefrontal cortex to lateral septum suppresses interaction with familiar mice. Cell 186, 4152–4171 (2023).
Li, L. et al. Social trauma engages lateral septum circuitry to occlude social reward. Nature 613, 696–703 (2023).
Chen, G. et al. Cellular and circuit architecture of the lateral septum for reward processing. Neuron 112, 2783–2798 (2024).
Goode, T. D. et al. A dorsal hippocampus-prodynorphinergic dorsolateral septum-to-lateral hypothalamus circuit mediates contextual gating of feeding. Neuron https://doi.org/10.1016/j.neuron.2026.01.025 (2026).
Besnard, A. et al. Dorsolateral septum somatostatin interneurons gate mobility to calibrate context-specific behavioral fear responses. Nat. Neurosci. 22, 436–446 (2019).
Brady, J. V. & Nauta, W. J. H. Subcortical mechanisms in emotional behavior: affective changes following septal forebrain lesions in the albino rat. J. Comp. Physiol. Psych. 46, 339–346 (1953).
Albert, D. J. & Wong, R. C. Hyperreactivity, muricide, and intraspecific aggression in the rat produced by infusion of local anesthetic into the lateral septum or surrounding areas. J. Comp. Physiol. Psych. 92, 1062–1073 (1978).
Ramirez, J. M., Salas, C. & Portavella, M. Offense and defense after lateral septal lesions in Columba Livia. Int. J. Neurosci. 41, 241–250 (1988).
Paxinos, G. The septum: neural systems involved in eating, drinking, irritability, muricide, copulation, and activity in rats. J. Comp. Physiol. Psych. 89, 1154–1168 (1975).
Reis, D. G., Scopinho, A. A., Guimarães, F. S., Corrêa, F. M. A. & Resstel, L. B. M. Involvement of the lateral septal area in the expression of fear conditioning to context. Learn. Mem. 17, 134–138 (2010).
Calandreau, L., Desgranges, B., Jaffard, R. & Desmedt, A. Switching from contextual to tone fear conditioning and vice versa: The key role of the glutamatergic hippocampal-lateral septal neurotransmission. Learn. Mem. 17, 440–443 (2010).
Radulovic, J., Rühmann, A., Liepold, T. & Spiess, J. Modulation of learning and anxiety by corticotropin-releasing factor (CRF) and stress: differential roles of CRF receptors 1 and 2. J. Neurosci. 19, 5016–5025 (1999).
Henry, B., Vale, W. & Markou, A. The effect of lateral septum corticotropin-releasing factor receptor 2 activation on anxiety is modulated by stress. J. Neurosci. 26, 9142–9152 (2006).
Todorovic, C. et al. Differential activation of CRF receptor subtypes removes stress-induced memory deficit and anxiety. Eur. J. Neurosci. 25, 3385–3397 (2007).
Turner, V. S., O’Sullivan, R. O. & Kheirbek, M. A. Linking external stimuli with internal drives: A role for the ventral hippocampus. Curr. Opin. Neurobiol. 76, 102590 (2022).
Biane, J. S. et al. Neural dynamics underlying associative learning in the dorsal and ventral hippocampus. Nat. Neurosci. 26, 798–809 (2023).
Sternson, S. M. Hypothalamic survival circuits: blueprints for purposive behaviors. Neuron 77, 810–824 (2013).
Jercog, D. et al. Dynamical prefrontal population coding during defensive behaviours. Nature 595, 690–694 (2021).
Mahn, M. et al. High-efficiency optogenetic silencing with soma-targeted anion-conducting channelrhodopsins. Nat. Commun. 9, 4125 (2018).
Heekeren, H. R., Marrett, S. & Ungerleider, L. G. The neural systems that mediate human perceptual decision making. Nat. Rev. Neurosci. 9, 467–479 (2008).
Evans, D. A., Stempel, A. V., Vale, R. & Branco, T. Cognitive control of escape behaviour. Trends Cogn. Sci. 23, 334–348 (2019).
Bentz, D. & Schiller, D. Threat processing: models and mechanisms. Wiley Interdiscip. Rev. Cogn. Sci. 6, 427–439 (2015).
Lee, J. & Sabatini, B. L. Striatal indirect pathway mediates exploration via collicular competition. Nature 599, 645–649 (2021).
Gray, J. A. & McNaughton, N. Comparison between the behavioural effects of septal and hippocampal lesions: A review. Neurosci. Biobehav. Rev. 7, 119–188 (1983).
Sibole, W., Miller, J. J. & Mogenson, G. J. Effects of septal stimulation on drinking elicited by electrical stimulation of the lateral hypothalamus. Exp. Neurol. 32, 466–477 (1971).
Azevedo, E. P. et al. A limbic circuit selectively links active escape to food suppression. eLife 9, e58894 (2020).
Shin, S. et al. Drd3 signaling in the lateral septum mediates early life stress-induced social dysfunction. Neuron 97, 195–208 (2018).
Rodriguez, L. A. et al. TrkB-dependent regulation of molecular signaling across septal cell types. Transl. Psychiatry 14, 52 (2024).
Simon, R. C. et al. Opioid-driven disruption of the septal complex reveals a role for neurotensin-expressing neurons in withdrawal. Neuron 113, 2325–2343.e9 (2025).
Reid, C. M. et al. Multimodal classification of neurons in the lateral septum. Preprint at bioRxiv https://doi.org/10.1101/2024.02.15.580381 (2024).
Hughes, A. C. et al. A single-vector intersectional AAV strategy for interrogating cellular diversity and brain function. Nat. Neurosci. 27, 1400–1410 (2024).
Kepecs, A. & Fishell, G. Interneuron cell types are fit to function. Nature 505, 318–326 (2014).
Luo, A. H., Tahsili-Fahadan, P., Wise, R. A., Lupica, C. R. & Aston-Jones, G. Linking context with reward: a functional circuit from hippocampal CA3 to ventral tegmental area. Science 333, 353–357 (2011).
Goode, T. et al. 141. Calibration of context-evoked feeding by a genetically defined lateral septum to lateral hypothalamus circuit. Biol. Psychiatry 93, S151 (2023).
Tingley, D. & Buzsáki, G. Transformation of a spatial map across the hippocampal-lateral septal circuit. Neuron 98, 1229–1242 (2018).
Tingley, D. & Buzsáki, G. Routing of hippocampal ripples to subcortical structures via the lateral septum. Neuron 105, 138–149 (2020).
Mogg, K. & Bradley, B. P. Anxiety and threat-related attention: cognitive-motivational framework and treatment. Trends Cogn. Sci. 22, 225–240 (2018).
Sussman, T. J., Jin, J. & Mohanty, A. Top-down and bottom-up factors in threat-related perception and attention in anxiety. Biol. Psychol. 121, 160–172 (2016).
Bishop, S. J. Neural mechanisms underlying selective attention to threat. Ann. N. Y. Acad. Sci. 1129, 141–152 (2008).
Rauss, K. & Pourtois, G. What is bottom-up and what is top-down in predictive coding? Front. Psychol. 4, 276 (2013).
Reardon, T. R. et al. Rabies virus CVS-N2cΔG strain enhances retrograde synaptic transfer and neuronal viability. Neuron 89, 711–724 (2016).
Sumser, A., Joesch, M., Jonas, P. & Ben-Simon, Y. Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. eLife 11, e79848 (2022).
Zhang, X. et al. Genetically identified amygdala–striatal circuits for valence-specific behaviors. Nat. Neurosci. 24, 1586–1600 (2021).
Ma, J. et al. Divergent projections of the paraventricular nucleus of the thalamus mediate the selection of passive and active defensive behaviors. Nat. Neurosci. 24, 1429–1440 (2021).
Xiao, X. et al. A genetically defined compartmentalized striatal direct pathway for negative reinforcement. Cell 183, 211–227 (2020).
LeDuke, D. O., Borio, M., Miranda, R. & Tye, K. M. Anxiety and depression: A top-down, bottom-up model of circuit function. Ann. N. Y. Acad. Sci. 1525, 70–87 (2023).
Wong, L. C. et al. Effective modulation of male aggression through lateral septum to medial hypothalamus projection. Curr. Biol. 26, 593–604 (2016).
Leroy, F. et al. A circuit from hippocampal CA2 to lateral septum disinhibits social aggression. Nature 564, 213–218 (2018).
Prescott, S. L., Umans, B. D., Williams, E. K., Brust, R. D. & Liberles, S. D. An airway protection program revealed by sweeping genetic control of vagal afferents. Cell 181, 574–589 (2020).
Matho, K. S. et al. Genetic dissection of the glutamatergic neuron system in cerebral cortex. Nature 598, 182–187 (2021).
Rossi, J. et al. Melanocortin-4 receptors expressed by cholinergic neurons regulate energy balance and glucose homeostasis. Cell Metab. 13, 195–204 (2011).
Williams, E. K. et al. Sensory neurons that detect stretch and nutrients in the digestive system. Cell 166, 209–221 (2016).
Pan, W. et al. Essential role for hypothalamic calcitonin receptor-expressing neurons in the control of food intake by leptin. Endocrinology 159, 1860–1872 (2018).
Rousso, D. L. et al. Two pairs of ON and OFF retinal ganglion cells are defined by intersectional patterns of transcription factor expression. Cell Rep. 15, 1930–1944 (2016).
Trusel, M. et al. Punishment-predictive cues guide avoidance through potentiation of hypothalamus-to-habenula synapses. Neuron 102, 120–127 (2019).
Weinreb, C. et al. Keypoint-MoSeq: parsing behavior by linking point tracking to pose dynamics. Nat. Methods 21, 1329–1339 (2024).
Arch, V. S. & Narins, P. M. ‘Silent’ signals: selective forces acting on ultrasonic communication systems in terrestrial vertebrates. Animal Behaviour 76, 1423–1428 (2008).
Kennedy, A. et al. Stimulus-specific hypothalamic encoding of a persistent defensive state. Nature 586, 730–734 (2020).
Hersman, S., Allen, D., Hashimoto, M., Brito, S. I. & Anthony, T. E. Stimulus salience determines defensive behaviors elicited by aversively conditioned serial compound auditory stimuli. eLife 9, e53803 (2020).
Dinç, F. et al. Fast, scalable, and statistically robust cell extraction from large-scale neural calcium imaging datasets. Preprint at bioRxiv https://doi.org/10.1101/2021.03.24.436279 (2024).
Pachitariu, M. et al. Suite2p: beyond 10,000 neurons with standard two-photon microscopy. Preprint at bioRxiv https://doi.org/10.1101/061507 (2017).
Burgess, C. R. et al. Hunger-dependent enhancement of food cue responses in mouse postrhinal cortex and lateral amygdala. Neuron 91, 1154–1169 (2016).

