1.
Nieh, E. H. et al. Inhibitory input from the lateral hypothalamus to
the ventral tegmental area disinhibits dopamine neurons and
promotes behavioral activation. Neuron 90, 1286–1298 (2016).
18
A Self-archived copy in
Kyoto University Research Information Repository
https://repository.kulib.kyoto-u.ac.jp
Article
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
Xiao, C. et al. Cholinergic mesopontine signals govern locomotion
and reward through dissociable midbrain pathways. Neuron 90,
333–347 (2016).
Li, Y. et al. Rostral and caudal ventral tegmental area GABAergic
inputs to different dorsal raphe neurons participate in opioid
dependence. Neuron 101, 748–761.e5 (2019).
Tan, K. R. et al. GABA neurons of the VTA drive conditioned place
aversion. Neuron 73, 1173–1183 (2012).
LeGates, T. A. et al. Reward behaviour is regulated by the strength
of hippocampus–nucleus accumbens synapses. Nature 564,
258–262 (2018).
Golden, S. A. et al. Basal forebrain projections to the lateral
habenula modulate aggression reward. Nature 534,
688–692 (2016).
Kim, J. et al. Rapid, biphasic CRF neuronal responses encode
positive and negative valence. Nat. Neurosci. 22,
576–585 (2019).
Matsumoto, M. & Hikosaka, O. Two types of dopamine neuron
distinctly convey positive and negative motivational signals. Nature 459, 837–841 (2009).
Paton, J. J., Belova, M. A., Morrison, S. E. & Salzman, C. D. The
primate amygdala represents the positive and negative value of
visual stimuli during learning. Nature 439, 865–870 (2006).
Hayashi, K., Nakao, K. & Nakamura, K. Appetitive and aversive
information coding in the primate dorsal raphé nucleus. J. Neurosci. 35, 6195–6208 (2015).
Volkow, N. D. & Morales, M. The brain on drugs: from reward to
addiction. Cell 162, 712–725 (2015).
Hu, H. Reward and aversion. Annu. Rev. Neurosci. 39,
297–324 (2016).
Kranz, G. S., Kasper, S. & Lanzenberger, R. Reward and the serotonergic system. Neuroscience 166, 1023–1035 (2010).
Liu, Z. et al. Dorsal raphe neurons signal reward through 5-HT and
glutamate. Neuron 81, 1360–1374 (2014).
Nagai, Y. et al. The role of dorsal raphe serotonin neurons in the
balance between reward and aversion. Int. J. Mol. Sci. 21,
2160 (2020).
Li, Y. et al. Serotonin neurons in the dorsal raphe nucleus encode
reward signals. Nat. Commun. 7, 10503 (2016).
Zhong, W., Li, Y., Feng, Q. & Luo, M. Learning and stress shape the
reward response patterns of serotonin neurons. J. Neurosci. 37,
8863–8875 (2017).
Inaba, K. et al. Neurons in monkey dorsal raphe nucleus code
beginning and progress of step-by-step schedule, reward
expectation, and amount of reward outcome in the reward schedule task. J. Neurosci. 33, 3477–3491 (2013).
Cohen, J. Y., Amoroso, M. W. & Uchida, N. Serotonergic neurons
signal reward and punishment on multiple timescales. eLife 4,
e06346 (2015).
Nakamura, K., Matsumoto, M. & Hikosaka, O. Reward-dependent
modulation of neuronal activity in the primate dorsal raphe
nucleus. J. Neurosci. 28, 5331–5343 (2008).
Bromberg-Martin, E. S., Hikosaka, O. & Nakamura, K. Coding of
task reward value in the dorsal raphe nucleus. J. Neurosci. 30,
6262–6272 (2010).
Risinger, F. O. Fluoxetine’s effects on ethanol’s rewarding, aversive and stimulus properties. Life Sci. 61, PL 235–PL 242 (1997).
Subhan, F., Deslandes, P. N., Pache, D. M. & Sewell, R. D. E. Do
antidepressants affect motivation in conditioned place preference? Eur. J. Pharmacol. 408, 257–263 (2000).
Hiranita, T., Soto, P. L., Newman, A. H. & Katz, J. L. Assessment of reinforcing effects of benztropine analogs and their
effects on cocaine self-administration in rats: comparisons
with monoamine uptake inhibitors. J. Pharmacol. Exp. Ther.
329, 677–686 (2009).
Nature Communications | (2022)13:7708
https://doi.org/10.1038/s41467-022-35346-7
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
Nutt, D. et al. The other face of depression, reduced positive
affect: the role of catecholamines in causation and cure. J. Psychopharmacol. 21, 461–471 (2007).
Bosker, F. J., Klompmakers, A. A. & Westenberg, H. G. M. Effects of
single and repeated oral administration of fluvoxamine on extracellular serotonin in the median raphe nucleus and dorsal hippocampus of the rat. Neuropharmacology 34, 501–508 (1995).
Romero, L., Bel, N., Artigas, F., de Montigny, C. & Blier, P. Effect of
pindolol on the function of pre- and postsynaptic 5-HT1A receptors: in vivo microdialysis and electrophysiological studies in the
rat brain. Neuropsychopharmacology 15, 349–360 (1996).
McQuade, R. & Sharp, T. Functional mapping of dorsal and median
raphe 5-hydroxytryptamine pathways in forebrain of the rat using
microdialysis. J. Neurochem. 69, 791–796 (1997).
Fletcher, P. J., Ming, Z. H. & Higgins, G. A. Conditioned place
preference induced by microinjection of 8-OH-DPAT into the
dorsal or median raphe nucleus. Psychopharmacology 113,
31–36 (1993).
Dzung Lê, A. et al. Intra-median raphe nucleus (MRN) infusions of
muscimol, a GABA-A receptor agonist, reinstate alcohol seeking in
rats: role of impulsivity and reward. Psychopharmacology 195,
605–615 (2008).
Graeff, F. G. & Silveira Filho, N. G. Behavioral inhibition induced by
electrical stimulation of the median raphe nucleus of the rat.
Physiol. Behav. 21, 477–484 (1978).
Szőnyi, A. et al. Median raphe controls acquisition of negative
experience in the mouse. Science 366, eaay8746 (2019).
Chen, T. W. et al. Ultrasensitive fluorescent proteins for imaging
neuronal activity. Nature 499, 295–300 (2013).
Nagai, T. et al. A variant of yellow fluorescent protein with fast and
efficient maturation for cell-biological applications. Nat. Biotechnol. 20, 87–90 (2002).
Nishitani, N. et al. Manipulation of dorsal raphe serotonergic
neurons modulates active coping to inescapable stress and
anxiety-related behaviors in mice and rats. Neuropsychopharmacology 44, 721–732 (2019).
Tzschentke, T. M. Measuring reward with the conditioned place
preference paradigm: a comprehensive review of drug effects,
recent progress and new issues. Prog. Neurobiol. 56,
613–672 (1998).
Mattis, J. et al. Principles for applying optogenetic tools derived
from direct comparative analysis of microbial opsins. Nat. Methods 9, 159–172 (2012).
Curzon, P., Rustay, N. R. & Browman, K. E. Cued and contextual
fear conditioning for rodents. In: Methods of Behavior Analysis in
Neuroscience 2nd edn (CRC Press, 2009)
Hochbaum, D. R. et al. All-optical electrophysiology in mammalian
neurons using engineered microbial rhodopsins. Nat. Methods 11,
825–833 (2014).
Tanaka, K. F. et al. Expanding the repertoire of optogenetically
targeted cells with an enhanced gene expression system. Cell
Rep. 2, 397–406 (2012).
Ohmura, Y., Tanaka, K. F., Tsunematsu, T., Yamanaka, A. & Yoshioka, M. Optogenetic activation of serotonergic neurons enhances
anxiety-like behaviour in mice. Int. J. Neuropsychopharmacol. 17,
1777–1783 (2014).
Berridge, K. C. Measuring hedonic impact in animals and infants:
microstructure of affective taste reactivity patterns. Neurosci.
Biobehav. Rev. 24, 173–198 (2000).
Dolensek, N., Gehrlach, D. A., Klein, A. S. & Gogolla, N. Facial
expressions of emotion states and their neuronal correlates in
mice. Science 368, 89–94 (2020).
Ables, J. L. et al. Retrograde inhibition by a specific subset of
interpeduncular α5 nicotinic neurons regulates nicotine preference. Proc. Natl Acad. Sci. USA 114, 13012–13017 (2017).
19
A Self-archived copy in
Kyoto University Research Information Repository
https://repository.kulib.kyoto-u.ac.jp
Article
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
57.
58.
59.
60.
61.
62.
63.
64.
Wolfman, S. L. et al. Nicotine aversion is mediated by GABAergic
interpeduncular nucleus inputs to laterodorsal tegmentum. Nat.
Commun. 9, 2710 (2018).
Muzerelle, A., Scotto-Lomassese, S., Bernard, J. F., Soiza-Reilly, M.
& Gaspar, P. Conditional anterograde tracing reveals distinct targeting of individual serotonin cell groups (B5–B9) to the forebrain
and brainstem. Brain Struct. Funct. 221, 535–561 (2016).
Fowler, C. D., Lu, Q., Johnson, P. M., Marks, M. J. & Kenny, P. J.
Habenular α5 nicotinic receptor subunit signalling controls nicotine intake. Nature 471, 597–601 (2011).
Glick, S. D., Ramirez, R. L., Livi, J. M. & Maisonneuve, I. M. 18Methoxycoronaridine acts in the medial habenula and/or interpeduncular nucleus to decrease morphine self-administration in
rats. Eur. J. Pharmacol. 537, 94–98 (2006).
Boulos, L. J. et al. Mu opioid receptors in the medial habenula
contribute to naloxone aversion. Neuropsychopharmacology 45,
247–255 (2020).
Pentkowski, N. S., Blanchard, D. C., Lever, C., Litvin, Y. & Blanchard, R. J. Effects of lesions to the dorsal and ventral hippocampus on defensive behaviors in rats. Eur. J. Neurosci. 23,
2185–2196 (2006).
Schumacher, A., Vlassov, E. & Ito, R. The ventral hippocampus, but
not the dorsal hippocampus is critical for learned approachavoidance decision making. Hippocampus 26, 530–542 (2016).
Broussard, G. J. et al. In vivo measurement of afferent activity with
axon-specific calcium imaging. Nat. Neurosci. 21,
1272–1280 (2018).
Sengupta, A. & Holmes, A. A discrete dorsal raphe to basal
amygdala 5-HT circuit calibrates aversive memory. Neuron 103,
489–505.e7 (2019).
Hagsäter, S. M. et al. A complex impact of systemically administered 5-HT2A receptor ligands on conditioned fear. Int. J. Neuropsychopharmacol. 24, 749–757 (2021).
Macedo, C. E., Martinez, R. C. R., Albrechet-Souza, L., Molina, V. A.
& Brandão, M. L. 5-HT2- and D1-mechanisms of the basolateral
nucleus of the amygdala enhance conditioned fear and impair
unconditioned fear. Behav. Brain Res. 177, 100–108 (2007).
Olivier, B. Serotonin: a never-ending story. Eur. J. Pharmacol. 753,
2–18 (2015).
Fernandez, S. P. et al. Constitutive and acquired serotonin deficiency alters memory and hippocampal synaptic plasticity. Neuropsychopharmacology 42, 512–523 (2017).
Matsumoto, M. & Hikosaka, O. Lateral habenula as a source of
negative reward signals in dopamine neurons. Nature 447,
1111–1115 (2007).
Zhu, Y., Wienecke, C. F. R., Nachtrab, G. & Chen, X. A thalamic
input to the nucleus accumbens mediates opiate dependence.
Nature 530, 219–222 (2016).
Zhao-Shea, R., Liu, L., Pang, X., Gardner, P. D. & Tapper, A. R.
Activation of GABAergic neurons in the interpeduncular nucleus
triggers physical nicotine withdrawal symptoms. Curr. Biol. 23,
2327–2335 (2013).
Zaniewska, M., McCreary, A. C., Wydra, K. & Filip, M. Effects of
serotonin (5-HT)2 receptor ligands on depression-like behavior
during nicotine withdrawal. Neuropharmacology 58,
1140–1146 (2010).
Malin, D. et al. Inverse agonists of the 5-HT2A receptor reduce
nicotine withdrawal signs in rats. Neurosci. Lett. 713, 134524 (2019).
Chalmers, D. T. & Watson, S. J. Comparative anatomical distribution of 5-HT1A receptor mRNA and 5-HT1A binding in rat brain—a
combined in situ hybridisation/in vitro receptor autoradiographic
study. Brain Res. 561, 51–60 (1991).
Bruinvels, A. T. et al. Localization of 5-HT1B, 5-HT1Dα, 5-HT1E and
5-HT1F receptor messenger RNA in rodent and primate brain.
Neuropharmacology 33, 367–386 (1994).
Nature Communications | (2022)13:7708
https://doi.org/10.1038/s41467-022-35346-7
65.
66.
67.
68.
69.
70.
71.
72.
73.
74.
75.
76.
77.
78.
79.
80.
81.
82.
83.
84.
Jakeman, L. B., To, Z. P., Eglen, R. M., Wong, E. H. & Bonhaus, D. W.
Quantitative autoradiography of 5-HT4 receptors in brains of three
species using two structurally distinct radioligands, [3H]GR113808
and [3H]BIMU-1. Neuropharmacology 33, 1027–1038 (1994).
Nishitani, N. et al. CRISPR/Cas9-mediated in vivo gene editing
reveals that neuronal 5-HT1A receptors in the dorsal raphe nucleus
contribute to body temperature regulation in mice. Brain Res.
1719, 243–252 (2019).
Lima, L. B. et al. Afferent and efferent connections of the interpeduncular nucleus with special reference to circuits involving the
habenula and raphe nuclei. J. Comp. Neurol. 525, 2411–2442 (2017).
Lammel, S. et al. Input-specific control of reward and aversion in
the ventral tegmental area. Nature 491, 212–217 (2012).
de Jong, J. W. et al. A neural circuit mechanism for encoding
aversive stimuli in the mesolimbic dopamine system. Neuron 101,
133–151.e7 (2019).
Wang, H. L. et al. Dorsal raphe dual serotonin-glutamate neurons
drive reward by establishing excitatory synapses on VTA
mesoaccumbens dopamine neurons. Cell Rep. 26,
1128–1142.e7 (2019).
Okaty, B. W. et al. Multi-scale molecular deconstruction of the
serotonin neuron system. Neuron 88, 774–791 (2015).
Ren, J. et al. Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe
nuclei. eLife 8, e49424 (2019).
Graeff, F. G., Quintero, S. & Gray, J. A. Median raphe stimulation,
hippocampal theta rhythm and threat-induced behavioral inhibition. Physiol. Behav. 25, 253–261 (1980).
Vertes, R. P., Kinney, G. G., Kocsis, B. & Fortin, W. J. Pharmacological suppression of the median raphe nucleus with serotonin1A
agonists, 8-OH-DPAT and buspirone, produces hippocampal theta
rhythm in the rat. Neuroscience 60, 441–451 (1994).
Kusljic, S., Copolov, D. L. & van den Buuse, M. Differential role of
serotonergic projections arising from the dorsal and median raphe
nuclei in locomotor hyperactivity and prepulse inhibition. Neuropsychopharmacology 28, 2138–2147 (2003).
Kocsis, B., Varga, V., Dahan, L. & Sik, A. Serotonergic neuron
diversity: identification of raphe neurons with discharges timelocked to the hippocampal theta rhythm. Proc. Natl Acad. Sci. USA
103, 1059–1064 (2006).
Huang, W., Ikemoto, S. & Wang, D. V. Median raphe nonserotonergic neurons modulate hippocampal theta oscillations. J.
Neurosci. 42, 1987–1998 (2022).
Ohmura, Y. et al. The serotonergic projection from the median
raphe nucleus to the ventral hippocampus is involved in the
retrieval of fear memory through the corticotropin-releasing factor type 2 receptor. Neuropsychopharmacology 35,
1271–1278 (2010).
Ohmura, Y. et al. Different roles of distinct serotonergic pathways
in anxiety-like behavior, antidepressant-like, and anti-impulsive
effects. Neuropharmacology 167, 107703 (2020).
Yoshida, K., Drew, M. R., Mimura, M. & Tanaka, K. F. Serotoninmediated inhibition of ventral hippocampus is required for sustained goal-directed behavior. Nat. Neurosci. 22, 770–777 (2019).
Ohmura, Y. et al. Serotonin 5-HT7 receptor in the ventral hippocampus modulates the retrieval of fear memory and stressinduced defecation. Int. J. Neuropsychopharmacol. 19, 1–12 (2016).
Luchetti, A. et al. Two functionally distinct serotonergic projections into hippocampus. J. Neurosci. 40, 4936–4944 (2020).
Kobayashi, Y. et al. Genetic dissection of medial habenulainterpeduncular nucleus pathway function in mice. Front. Behav.
Neurosci. 7, 17 (2013).
Xu, C. et al. Medial habenula-interpeduncular nucleus circuit
contributes to anhedonia-like behavior in a rat model of depression. Front. Behav. Neurosci. 12, 238 (2018).
20
A Self-archived copy in
Kyoto University Research Information Repository
https://repository.kulib.kyoto-u.ac.jp
Article
85.
86.
87.
88.
89.
90.
91.
92.
93.
94.
95.
96.
97.
98.
99.
100.
101.
102.
103.
104.
Shih, P. Y. et al. Differential expression and function of nicotinic
acetylcholine receptors in subdivisions of medial habenula. J.
Neurosci. 34, 9789–9802 (2014).
McCallum, S. E., Cowe, M. A., Lewis, S. W. & Glick, S. D. α3β4
nicotinic acetylcholine receptors in the medial habenula modulate the mesolimbic dopaminergic response to acute nicotine
in vivo. Neuropharmacology 63, 434–440 (2012).
Salas, R., Sturm, R., Boulter, J. & De Biasi, M. Nicotinic receptors in
the habenulo-interpeduncular system are necessary for nicotine
withdrawal in mice. J. Neurosci. 29, 3014–3018 (2009).
Saleeba, C., Dempsey, B., Le, S., Goodchild, A. & McMullan, S. A
student’s guide to neural circuit tracing. Front. Neurosci. 13,
897 (2019).
Franklin, K. B. J. & Paxinos, G. The Mouse Brain in Stereotaxic
Coordinates 3rd edn (Academic Press, 2007).
Yang, H. et al. Nucleus accumbens subnuclei regulate motivated
behavior via direct inhibition and disinhibition of VTA dopamine
subpopulations. Neuron 97, 434–449.e4 (2018).
Yang, H. et al. Pain modulates dopamine neurons via a
spinal–parabrachial–mesencephalic circuit. Nat. Neurosci. 24,
1402–1413 (2021).
Shikanai, H. et al. Distinct neurochemical and functional properties of GAD67-containing 5-HT neurons in the rat dorsal raphe
nucleus. J. Neurosci. 32, 14415–14426 (2012).
Nakamura, K., Sato, T., Ohashi, A., Tsurui, H. & Hasegawa, H. Role
of a serotonin precursor in development of gut microvilli. Am. J.
Pathol. 172, 333–344 (2008).
Gunaydin, L. A. et al. Natural neural projection dynamics underlying social behavior. Cell 157, 1535–1551 (2014).
Kim, C. K. et al. Simultaneous fast measurement of circuit
dynamics at multiple sites across the mammalian brain. Nat.
Methods 13, 325–328 (2016).
Edelstein, A. D. et al. Advanced methods of microscope control
using μManager software. J. Biol. Methods 1, e10 (2014).
Zhang, T. et al. Activation of GABAergic neurons in the nucleus
accumbens mediates the expression of cocaine-associated
memory. Biol. Pharm. Bull. 41, 1084–1088 (2018).
Zhang, T. et al. Glutamatergic neurons in the medial prefrontal
cortex mediate the formation and retrieval of cocaine-associated
memories in mice. Addict. Biol. 25, e12723 (2020).
Fletcher, P. J., Grottick, A. J. & Higgins, G. A. Differential effects
of the 5-HT2A receptor antagonist M100,907 and the 5-HT2C
receptor antagonist SB242,084 on cocaine-induced locomotor
activity, cocaine self-administration and cocaine-induced
reinstatement of responding. Neuropsychopharmacology 27,
576–586 (2002).
Boutrel, B., Monaca, C., Hen, R., Hamon, M. & Adrien, J. Involvement of 5-HT1A receptors in homeostatic and stress-induced
adaptive regulations of paradoxical sleep: studies in 5-HT1A knockout mice. J. Neurosci. 22, 4686–4692 (2002).
Smith, R. L., Barrett, R. J. & Sanders-Bush, E. Discriminative stimulus properties of 1-(2,5-dimethoxy-4-iodophenyl)−2-aminopropane [(±)DOI] in C57BL/6J mice. Psychopharmacology 166,
61–68 (2003).
Taylor, S. R. et al. GABAergic and glutamatergic efferents of the
mouse ventral tegmental area. J. Comp. Neurol. 522,
3308–3334 (2014).
Nunes-de-Souza, R. L., Canto-de-Souza, A. & Rodgers, R. J. Effects
of intra-hippocampal infusion of WAY-100635 on plus-maze
behavior in mice: influence of site of injection and prior test
experience. Brain Res. 927, 87–96 (2002).
Canto-de-Souza, A., Nunes-de-Souza, R. L. & Rodgers, R. J.
Anxiolytic-like effect of way-100635 microinfusions into the
median (but not dorsal) raphe nucleus in mice exposed to the
Nature Communications | (2022)13:7708
https://doi.org/10.1038/s41467-022-35346-7
105.
106.
107.
108.
109.
plus-maze: influence of prior test experience. Brain Res. 928,
50–59 (2002).
Nair, S. G. et al. Role of dorsal medial prefrontal cortex dopamine
D1-family receptors in relapse to high-fat food seeking induced by
the anxiogenic drug yohimbine. Neuropsychopharmacology 36,
497–510 (2011).
Toda, K. et al. Nigrotectal stimulation stops interval timing in mice.
Curr. Biol. 27, 3763–3770.e3 (2017).
Kirihara, Y., Takechi, M., Kurosaki, K., Kobayashi, Y. & Kurosawa,
T. Anesthetic effects of a mixture of medetomidine, midazolam
and butorphanol in two strains of mice. Exp. Anim. 62,
173–180 (2013).
Grill, H. J. & Berridge, K. C. Taste reactivity measure of neural
palatability. In Progress in Psychobiology and Physiological Psychology. 11, 1–61 (Academic Press, 1985).
Berndt, A., Yizhar, O., Gunaydin, L. A., Hegemann, P. & Deisseroth,
K. Bi-stable neural state switches. Nat. Neurosci. 12,
229–234 (2009).
Acknowledgements
We would like to thank Dr. Hiroyuki Hasegawa for kindly gifting us antitryptophan hydroxylase 2 antibodies. We would like to thank Drs. Akihiro
Yamanaka and Kenji F. Tanaka for kindly providing us with Tph2-tTA and
TetO-ChR2(C128S) mice. We would like to thank Dr. Hitomi Sasamori for
her help in the breeding of transgenic mice. We would like to thank Drs.
Mike Robinson and Kent Berridge for telling us how to conduct the surgery
of oral infusion. We would like to thank Hitoshi Saito for his help in programming. We would like to thank Dr. Masaaki Sato for kindly lending us
an infusion pump. We would like to thank Drs. Katsuyuki Kaneda and
Satoshi Deyama for help on the CPP/CPA tests. We would like to thank Drs.
Atsushi Miyawaki (pCSII-EF-Venus), Adam Cohen (CheRiff; addgene
#51694), Karl Deisseroth (eArchT; addgene #35513), Douglas Kim and
GENIE Project (GCaMP6s; addgene #40753), and Lin Tian (axon-GCaMP6s;
addgene #112008) for providing us the constructs. This work was supported by Grants-in-Aid for Scientific Research from JSPS (to K.Nagayasu
(JP20H04774, JP20K07064), to S.K. (JP18H04616, JP20H00491), to Y.O.
(21K07473), to M.Y. (21H02668), to M.Kondo (JP22K11498), Grant-in-Aid
for Nagai Memorial Research Scholarship from the Pharmaceutical
Society of Japan (to H.K. (N-184403)), Grants-in-Aid for JSPS Fellows
(to H.K. (JP20J12341), Y.N. (JP21J14215), and C.A. (JP21J21091)), AMED (to
S.K. (JP20ak0101088h0003, JP21ak0101153h0001), to M.Kondo
(JP21wm0525026, JP20lm0203007)), Smoking Research Foundation (to
Y.O.), The Shimizu Foundation for Immunology and Neuroscience Grant
(to K.Nagayasu), The Uehara Memorial Foundation (to K.Nagayasu), The
Lotte Foundation (to K.Nagayasu), Takeda Science Foundation (to
M.Kondo), SENSHIN Medical Research Foundation (M.Kondo).
Author contributions
H.K., Y.B., K.Nagayasu, Y.O., and S.K. designed the study. H.K. and Y.B.
contributed equally to this work. H.K. performed fiber photometry
experiments, optogenetic experiments, pharmacological experiments, behavioral experiments, AAV production, histochemical analyses, and data analyses with the help of M.Koda, H.M., C.A., M.H., H.S.,
and M.Kondo. Y.B., K.T., and Y.O. jointly constructed the head-fixed
behavioral setup, and Y.B. and Y.O. performed an optogenetic
intervention on licking behaviors and histochemical analyses. N.N.,
K.Niitani, S.I., and K.K. performed electrophysiological experiments.
N.N., Y.N., M.Koda, C.A., and K.Nagayasu constructed and produced
AAVs. H.K. wrote the paper draft. Y.B., K.Nagayasu, Y.O., and S.K.
jointly edited the paper. K.Nagayasu, Y.O., M.Y., and S.K. jointly
supervised the project.
Competing interests
The authors declare no competing interests.
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Additional information
Supplementary information The online version contains
supplementary material available at
https://doi.org/10.1038/s41467-022-35346-7.
Correspondence and requests for materials should be addressed to
Kazuki Nagayasu, Yu Ohmura or Shuji Kaneko.
Peer review information Nature Communications thanks Minmin Luo
and Katsuhiko Miyazaki for their contribution to the peer review of this
work. Peer reviewer reports are available.
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Nature Communications | (2022)13:7708
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