A discrete serotonergic circuit involved in the generation of tinnitus behavior
Edited by Moses V. Chao, New York University Langone Medical Center, New York, NY; received May 1, 2025; accepted February 13, 2026
Significance
Tinnitus, a prevalent hearing disorder linked to dysregulated serotonergic system, has poorly understood neural circuits. Using cutting-edge neuroscience tools, our study reveals a discrete 5-HTDRN→DCN circuit driving tinnitus in hyperserotonergic states. These findings highlight serotonin’s role in modulating sensory brain regions and identify circuit-level mechanisms of neurological disorders. Our work advances understanding of tinnitus and suggests targeted interventions.
Abstract
Although dysregulated serotonergic neurotransmission has been implicated in the pathophysiology of tinnitus, the precise neural circuit mechanisms underlying this complex sensory neurological disorder remain elusive. In the current study, we investigated whether a serotonergic input from the dorsal raphe nucleus (DRN) to the dorsal cochlear nucleus (DCN), a key auditory brain region whose hyperactivity is associated with tinnitus, modulates behaviors in mice consistent with the presence of tinnitus. Using neural tracing and viral-genetic methods, we identified an anatomically and functionally defined serotonergic subpopulation in the DRN that projects to the DCN (5-HTDRN→DCN neurons). Optogenetic activation of 5-HTDRN→DCN circuit increased spike activity in DCN fusiform cells, exhibiting characteristics consistent with tinnitus-like electrical hyperactivity. Chemogenetic activation of 5-HTDRN→DCN circuit induced tinnitus-related behaviors in mice, which was largely reversed by blocking 5-HT2A receptors. Additionally, we found that noise exposure increased 5-HT levels in the DCN and the activity of 5-HTDRN→DCN neurons in mice with noise-induced tinnitus-related behaviors. Importantly, chemogenetic inhibition of 5-HTDRN→DCN circuit ameliorated significantly noise-induced tinnitus–related behavior in mice. These results reveal that activation of 5-HTDRN→DCN circuit induces hyperactivity in the DCN sufficient for the perceptual generation and modulation of tinnitus. These findings provide direct evidence that 5-HT neurons in the DRN play an important role in tinnitus and facilitate our understanding of the circuit mechanisms of pathophysiology in sensory neurological disorders.
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Data, Materials, and Software Availability
All study data are included in the article and/or supporting information.
Acknowledgments
We thank Professor Stephen V. David for his technical assistance with extracellular single-unit recordings and Wen-Jun An and Yan-Lin Wu for their support with ABR testing. This work was supported by the Natural Science Foundation of China (Grants 32271059 and 82071061), NIH grant RO1DC004450, Anhui Province Clinical Medicine Research and Transformation Special Project (202304295107020125), Anhui Provincial Natural Science Foundation (2408085QH277), and by Natural Science Research Project of Anhui Educational Committee (2024AH050075).
Author contributions
Q.-W.W., L.O.T., and Z.-Q.T. designed research; M.-T.Y., Z.-Y.D., S.-X.W., K.-J.W., C.-H.Q., Y.-M.Z., X.-T.G., and C.-C.P. performed research; J.-Q.S., J.-W.S., W.-H.C., and Y.J. contributed new reagents/analytic tools; M.-T.Y., Z.-Y.D., S.-X.W., K.-J.W., C.-H.Q., Y.-M.Z., X.-T.G., and C.-C.P. analyzed data; and M.-T.Y., Z.-Y.D., S.-X.W., Q.-W.W., L.O.T., and Z.-Q.T. wrote the paper.
Competing interests
The authors declare no competing interest.
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References
1
A. J. Heller, Classification and epidemiology of tinnitus. Otolaryngol. Clin. North Am. 36, 239–248 (2003).
2
Y. C. Kumbul, Ü. Işik, F. Kiliç, M. E. Sivrice, V. Akin, Evaluation of anxiety sensitivity, anxiety, depression, and attention deficit hyperactivity disorder in patients with tinnitus. Noise Health 24, 13–19 (2022).
3
B. Hackenberg et al., Tinnitus and its relation to depression, anxiety, and stress-a population-based cohort study. J. Clin. Med. 12, 1169 (2023).
4
A. Henton, T. Tzounopoulos, What’s the buzz? The neuroscience and the treatment of tinnitus. Physiol. Rev. 101, 1609–1632 (2021).
5
A. Teissier et al., Activity of raphé serotonergic neurons controls emotional behaviors. Cell Rep. 13, 1965–1976 (2015).
6
J. Ren et al., Anatomically defined and functionally distinct dorsal raphe serotonin sub-systems. Cell 175, 472–487.e20 (2018).
7
C. M. Teixeira et al., Hippocampal 5-HT input regulates memory formation and Schaffer collateral excitation. Neuron 98, 992–1004.e4 (2018).
8
W.-J. Zou et al., A discrete serotonergic circuit regulates vulnerability to social stress. Nat. Commun. 11, 4218 (2020).
9
K. W. Huang et al., Molecular and anatomical organization of the dorsal raphe nucleus. Elife 8, e46464 (2019).
10
W. Zhou et al., A neural circuit for comorbid depressive symptoms in chronic pain. Nat. Neurosci. 22, 1649–1658 (2019).
11
L. Tikker et al., Inactivation of the GATA cofactor ZFPM1 results in abnormal development of dorsal raphe serotonergic neuron subtypes and increased anxiety-like behavior. J. Neurosci. 40, 8669–8682 (2020).
12
C. A. Marcinkiewcz et al., Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala. Nature 537, 97–101 (2016).
13
A. Sengupta, A. Holmes, A discrete dorsal raphe to basal amygdala 5-HT circuit calibrates aversive memory. Neuron 103, 489–505.e7 (2019).
14
Z. Liu, R. Lin, M. Luo, Reward contributions to serotonergic functions. Annu. Rev. Neurosci. 43, 141–162 (2020).
15
C. Morel et al., Midbrain projection to the basolateral amygdala encodes anxiety-like but not depression-like behaviors. Nat. Commun. 13, 1532 (2022).
16
R. Ogelman et al., Serotonin modulates excitatory synapse maturation in the developing prefrontal cortex. Nat. Commun. 15, 1368 (2024).
17
J. J. Simpson, W. E. Davies, A review of evidence in support of a role for 5-HT in the perception of tinnitus. Hear. Res. 145, 1–7 (2000).
18
F. Salvinelli, M. Casale, F. Paparo, A. M. Persico, C. Zini, Subjective tinnitus, temporomandibular joint dysfunction, and serotonin modulation of neural plasticity: Causal or casual triad? Med. Hypotheses 61, 446–448 (2003).
19
K. K. Caperton, A. M. Thompson, Activation of serotonergic neurons during salicylate-induced tinnitus. Otol. Neurotol. 32, 301–307 (2011).
20
P. Baldo, C. Doree, P. Molin, D. McFerran, S. Cecco, Antidepressants for patients with tinnitus. Cochrane Database Syst. Rev. 2012, CD003853 (2012).
21
J. Magagnoli, T. H. Cummings, J. W. Hardin, S. S. Sutton, J. Ambati, Fluoxetine, fluvoxamine, and hearing loss or tinnitus after cisplatin treatment: A retrospective cohort study. J. Investig. 72, 579–586 (2024).
22
C. W. T. Miller, Development of tinnitus at a low dose of sertraline: Clinical course and proposed mechanisms. Case Rep. Psychiatry 2016, 1790692 (2016).
23
A. P. Wand, Transient citalopram-induced auditory hallucinations in a patient with Parkinson’s disease and depression. Aust. N. Z. J. Psychiatry 46, 178 (2012).
24
H. Ağır, F. Coşkun, Citalopram associated with the development of tinnitus in an adolescent girl: A case report. J. Clin. Psychopharmacol. 45, 57–58 (2025).
25
H. Cransac, J. M. Cottet-Emard, S. Hellström, L. Peyrin, Specific sound-induced noradrenergic and serotonergic activation in central auditory structures. Hear. Res. 118, 151–156 (1998).
26
L.-Q. Cheng, F.-Q. Shu, M. Zhang, Y.-Z. Kai, Z.-Q. Tang, Resveratrol prevents hearing loss and a subregion specific- reduction of serotonin reuptake transporter induced by noise exposure in the central auditory system. Front. Neurosci. 17, 1134153 (2023).
27
T. J. Brozoski, C. A. Bauer, D. M. Caspary, Elevated fusiform cell activity in the dorsal cochlear nucleus of chinchillas with psychophysical evidence of tinnitus. J. Neurosci. 22, 2383–2390 (2002).
28
J. W. Middleton et al., Mice with behavioral evidence of tinnitus exhibit dorsal cochlear nucleus hyperactivity because of decreased GABAergic inhibition. Proc. Natl. Acad. Sci. U.S.A. 108, 7601–7606 (2011).
29
S. Dehmel, S. Pradhan, S. Koehler, S. Bledsoe, S. Shore, Noise overexposure alters long-term somatosensory-auditory processing in the dorsal cochlear nucleus–possible basis for tinnitus-related hyperactivity? J. Neurosci. 32, 1660–1671 (2012).
30
S. D. Koehler, S. E. Shore, Stimulus timing-dependent plasticity in dorsal cochlear nucleus is altered in tinnitus. J. Neurosci. 33, 19647–19656 (2013).
31
S. Li, V. Choi, T. Tzounopoulos, Pathogenic plasticity of Kv7.2/3 channel activity is essential for the induction of tinnitus. Proc. Natl. Acad. Sci. U.S.A. 110, 9980–9985 (2013).
32
S. Li, B. I. Kalappa, T. Tzounopoulos, Noise-induced plasticity of KCNQ2/3 and HCN channels underlies vulnerability and resilience to tinnitus. Elife 4, e07242 (2015).
33
C. Wu, D. T. Martel, S. E. Shore, Increased synchrony and bursting of dorsal cochlear nucleus fusiform cells correlate with tinnitus. J. Neurosci. 36, 2068–2073 (2016).
34
F. H. Willard, R. H. Ho, G. F. Martin, The neuronal types and the distribution of 5-hydroxytryptamine and enkephalin-like immunoreactive fibers in the dorsal cochlear nucleus of the North American opossum. Brain Res. Bull. 12, 253–266 (1984).
35
A. Klepper, H. Herbert, Distribution and origin of noradrenergic and serotonergic fibers in the cochlear nucleus and inferior colliculus of the rat. Brain Res. 557, 190–201 (1991).
36
G. C. Thompson, A. M. Thompson, K. M. Garrett, B. H. Britton, Serotonin and serotonin receptors in the central auditory system. Otolaryngol. Head Neck Surg. 110, 93–102 (1994).
37
A. M. Thompson, K. R. Moore, G. C. Thompson, Distribution and origin of serotoninergic afferents to guinea pig cochlear nucleus. J. Comp. Neurol. 351, 104–116 (1995).
38
T. Am, T. Gc, Serotonin projection patterns to the cochlear nucleus. Brain Res. 907, 195–207 (2001).
39
L. M. Hurley, A. M. Thompson, Serotonergic innervation of the auditory brainstem of the Mexican free-tailed bat, Tadarida brasiliensis. J. Comp. Neurol. 435, 78–88 (2001).
40
Z.-Q. Tang, L. O. Trussell, Serotonergic regulation of excitability of principal cells of the dorsal cochlear nucleus. J. Neurosci. 35, 4540–4551 (2015).
41
Z.-Q. Tang, L. O. Trussell, Serotonergic modulation of sensory representation in a central multisensory circuit is pathway specific. Cell Rep. 20, 1844–1854 (2017).
42
H. W. Steinbusch, Distribution of serotonin-immunoreactivity in the central nervous system of the rat-cell bodies and terminals. Neuroscience 6, 557–618 (1981).
43
M. M. Scott, K. C. Krueger, E. S. Deneris, A differentially autoregulated Pet-1 enhancer region is a critical target of the transcriptional cascade that governs serotonin neuron development. J. Neurosci. 25, 2628–2636 (2005).
44
D. Oertel, S. H. Wu, Morphology and physiology of cells in slice preparations of the dorsal cochlear nucleus of mice. J. Comp. Neurol. 283, 228–247 (1989).
45
B. N. Armbruster, X. Li, M. H. Pausch, S. Herlitze, B. L. Roth, Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand. Proc. Natl. Acad. Sci. U.S.A. 104, 5163–5168 (2007).
46
V. C. Torres Irizarry et al., Estrogen signaling in the dorsal raphe regulates binge-like drinking in mice. Transl. Psychiatry 14, 122 (2024).
47
S. Masri et al., Chemogenetic activation of cortical parvalbumin-positive interneurons reverses noise-induced impairments in gap detection. J. Neurosci. 41, 8848–8857 (2021).
48
M. Rezapour, M. Farrahizadeh, M. Akbari, Effectiveness of transcutaneous vagus nerve stimulation (tVNS) on salicylate-induced tinnitus. Neurosci. Lett. 822, 137639 (2024).
49
W. Wang et al., Neuroinflammation mediates noise-induced synaptic imbalance and tinnitus in rodent models. PLoS Biol. 17, e3000307 (2019).
50
F. Deng et al., Improved green and red GRAB sensors for monitoring spatiotemporal serotonin release in vivo. Nat. Methods 21, 692–702 (2024).
51
T.-W. Chen et al., Ultrasensitive fluorescent proteins for imaging neuronal activity. Nature 499, 295–300 (2013).
52
W. E. Allen et al., Thirst-associated preoptic neurons encode an aversive motivational drive. Science 357, 1149–1155 (2017).
53
L. Li et al., Dorsal raphe nucleus to anterior cingulate cortex 5-HTergic neural circuit modulates consolation and sociability. Elife 10, e67638 (2021).
54
A. Belmer, R. Depoortere, K. Beecher, A. Newman-Tancredi, S. E. Bartlett, Neural serotonergic circuits for controlling long-term voluntary alcohol consumption in mice. Mol. Psychiatry 27, 4599–4610 (2022).
55
M. A. Muniak, D. K. Ryugo, Tonotopic organization of vertical cells in the dorsal cochlear nucleus of the CBA/J mouse. J. Comp. Neurol. 522, 937–949 (2014).
56
J. Wan et al., A genetically encoded sensor for measuring serotonin dynamics. Nat. Neurosci. 24, 746–752 (2021).
57
J. Liu et al., Effects of salicylate on serotoninergic activities in rat inferior colliculus and auditory cortex. Hear. Res. 175, 45–53 (2003).
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Copyright © 2026 the Author(s). Published by PNAS. This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
Data, Materials, and Software Availability
All study data are included in the article and/or supporting information.
Submission history
Received: May 1, 2025
Accepted: February 13, 2026
Published online: April 20, 2026
Published in issue: April 28, 2026
Keywords
Acknowledgments
We thank Professor Stephen V. David for his technical assistance with extracellular single-unit recordings and Wen-Jun An and Yan-Lin Wu for their support with ABR testing. This work was supported by the Natural Science Foundation of China (Grants 32271059 and 82071061), NIH grant RO1DC004450, Anhui Province Clinical Medicine Research and Transformation Special Project (202304295107020125), Anhui Provincial Natural Science Foundation (2408085QH277), and by Natural Science Research Project of Anhui Educational Committee (2024AH050075).
Author contributions
Q.-W.W., L.O.T., and Z.-Q.T. designed research; M.-T.Y., Z.-Y.D., S.-X.W., K.-J.W., C.-H.Q., Y.-M.Z., X.-T.G., and C.-C.P. performed research; J.-Q.S., J.-W.S., W.-H.C., and Y.J. contributed new reagents/analytic tools; M.-T.Y., Z.-Y.D., S.-X.W., K.-J.W., C.-H.Q., Y.-M.Z., X.-T.G., and C.-C.P. analyzed data; and M.-T.Y., Z.-Y.D., S.-X.W., Q.-W.W., L.O.T., and Z.-Q.T. wrote the paper.
Competing interests
The authors declare no competing interest.
Notes
This article is a PNAS Direct Submission.
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A discrete serotonergic circuit involved in the generation of tinnitus behavior, Proc. Natl. Acad. Sci. U.S.A.
123 (17) e2509692123,
https://doi.org/10.1073/pnas.2509692123
(2026).
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References
References
References
1
A. J. Heller, Classification and epidemiology of tinnitus. Otolaryngol. Clin. North Am. 36, 239–248 (2003).
2
Y. C. Kumbul, Ü. Işik, F. Kiliç, M. E. Sivrice, V. Akin, Evaluation of anxiety sensitivity, anxiety, depression, and attention deficit hyperactivity disorder in patients with tinnitus. Noise Health 24, 13–19 (2022).
3
B. Hackenberg et al., Tinnitus and its relation to depression, anxiety, and stress-a population-based cohort study. J. Clin. Med. 12, 1169 (2023).
4
A. Henton, T. Tzounopoulos, What’s the buzz? The neuroscience and the treatment of tinnitus. Physiol. Rev. 101, 1609–1632 (2021).
5
A. Teissier et al., Activity of raphé serotonergic neurons controls emotional behaviors. Cell Rep. 13, 1965–1976 (2015).
6
J. Ren et al., Anatomically defined and functionally distinct dorsal raphe serotonin sub-systems. Cell 175, 472–487.e20 (2018).
7
C. M. Teixeira et al., Hippocampal 5-HT input regulates memory formation and Schaffer collateral excitation. Neuron 98, 992–1004.e4 (2018).
8
W.-J. Zou et al., A discrete serotonergic circuit regulates vulnerability to social stress. Nat. Commun. 11, 4218 (2020).
9
K. W. Huang et al., Molecular and anatomical organization of the dorsal raphe nucleus. Elife 8, e46464 (2019).
10
W. Zhou et al., A neural circuit for comorbid depressive symptoms in chronic pain. Nat. Neurosci. 22, 1649–1658 (2019).
11
L. Tikker et al., Inactivation of the GATA cofactor ZFPM1 results in abnormal development of dorsal raphe serotonergic neuron subtypes and increased anxiety-like behavior. J. Neurosci. 40, 8669–8682 (2020).
12
C. A. Marcinkiewcz et al., Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala. Nature 537, 97–101 (2016).
13
A. Sengupta, A. Holmes, A discrete dorsal raphe to basal amygdala 5-HT circuit calibrates aversive memory. Neuron 103, 489–505.e7 (2019).
14
Z. Liu, R. Lin, M. Luo, Reward contributions to serotonergic functions. Annu. Rev. Neurosci. 43, 141–162 (2020).
15
C. Morel et al., Midbrain projection to the basolateral amygdala encodes anxiety-like but not depression-like behaviors. Nat. Commun. 13, 1532 (2022).
16
R. Ogelman et al., Serotonin modulates excitatory synapse maturation in the developing prefrontal cortex. Nat. Commun. 15, 1368 (2024).
17
J. J. Simpson, W. E. Davies, A review of evidence in support of a role for 5-HT in the perception of tinnitus. Hear. Res. 145, 1–7 (2000).
18
F. Salvinelli, M. Casale, F. Paparo, A. M. Persico, C. Zini, Subjective tinnitus, temporomandibular joint dysfunction, and serotonin modulation of neural plasticity: Causal or casual triad? Med. Hypotheses 61, 446–448 (2003).
19
K. K. Caperton, A. M. Thompson, Activation of serotonergic neurons during salicylate-induced tinnitus. Otol. Neurotol. 32, 301–307 (2011).
20
P. Baldo, C. Doree, P. Molin, D. McFerran, S. Cecco, Antidepressants for patients with tinnitus. Cochrane Database Syst. Rev. 2012, CD003853 (2012).
21
J. Magagnoli, T. H. Cummings, J. W. Hardin, S. S. Sutton, J. Ambati, Fluoxetine, fluvoxamine, and hearing loss or tinnitus after cisplatin treatment: A retrospective cohort study. J. Investig. 72, 579–586 (2024).
22
C. W. T. Miller, Development of tinnitus at a low dose of sertraline: Clinical course and proposed mechanisms. Case Rep. Psychiatry 2016, 1790692 (2016).
23
A. P. Wand, Transient citalopram-induced auditory hallucinations in a patient with Parkinson’s disease and depression. Aust. N. Z. J. Psychiatry 46, 178 (2012).
24
H. Ağır, F. Coşkun, Citalopram associated with the development of tinnitus in an adolescent girl: A case report. J. Clin. Psychopharmacol. 45, 57–58 (2025).
25
H. Cransac, J. M. Cottet-Emard, S. Hellström, L. Peyrin, Specific sound-induced noradrenergic and serotonergic activation in central auditory structures. Hear. Res. 118, 151–156 (1998).
26
L.-Q. Cheng, F.-Q. Shu, M. Zhang, Y.-Z. Kai, Z.-Q. Tang, Resveratrol prevents hearing loss and a subregion specific- reduction of serotonin reuptake transporter induced by noise exposure in the central auditory system. Front. Neurosci. 17, 1134153 (2023).
27
T. J. Brozoski, C. A. Bauer, D. M. Caspary, Elevated fusiform cell activity in the dorsal cochlear nucleus of chinchillas with psychophysical evidence of tinnitus. J. Neurosci. 22, 2383–2390 (2002).
28
J. W. Middleton et al., Mice with behavioral evidence of tinnitus exhibit dorsal cochlear nucleus hyperactivity because of decreased GABAergic inhibition. Proc. Natl. Acad. Sci. U.S.A. 108, 7601–7606 (2011).
29
S. Dehmel, S. Pradhan, S. Koehler, S. Bledsoe, S. Shore, Noise overexposure alters long-term somatosensory-auditory processing in the dorsal cochlear nucleus–possible basis for tinnitus-related hyperactivity? J. Neurosci. 32, 1660–1671 (2012).
30
S. D. Koehler, S. E. Shore, Stimulus timing-dependent plasticity in dorsal cochlear nucleus is altered in tinnitus. J. Neurosci. 33, 19647–19656 (2013).
31
S. Li, V. Choi, T. Tzounopoulos, Pathogenic plasticity of Kv7.2/3 channel activity is essential for the induction of tinnitus. Proc. Natl. Acad. Sci. U.S.A. 110, 9980–9985 (2013).
32
S. Li, B. I. Kalappa, T. Tzounopoulos, Noise-induced plasticity of KCNQ2/3 and HCN channels underlies vulnerability and resilience to tinnitus. Elife 4, e07242 (2015).
33
C. Wu, D. T. Martel, S. E. Shore, Increased synchrony and bursting of dorsal cochlear nucleus fusiform cells correlate with tinnitus. J. Neurosci. 36, 2068–2073 (2016).
34
F. H. Willard, R. H. Ho, G. F. Martin, The neuronal types and the distribution of 5-hydroxytryptamine and enkephalin-like immunoreactive fibers in the dorsal cochlear nucleus of the North American opossum. Brain Res. Bull. 12, 253–266 (1984).
35
A. Klepper, H. Herbert, Distribution and origin of noradrenergic and serotonergic fibers in the cochlear nucleus and inferior colliculus of the rat. Brain Res. 557, 190–201 (1991).
36
G. C. Thompson, A. M. Thompson, K. M. Garrett, B. H. Britton, Serotonin and serotonin receptors in the central auditory system. Otolaryngol. Head Neck Surg. 110, 93–102 (1994).
37
A. M. Thompson, K. R. Moore, G. C. Thompson, Distribution and origin of serotoninergic afferents to guinea pig cochlear nucleus. J. Comp. Neurol. 351, 104–116 (1995).
38
T. Am, T. Gc, Serotonin projection patterns to the cochlear nucleus. Brain Res. 907, 195–207 (2001).
39
L. M. Hurley, A. M. Thompson, Serotonergic innervation of the auditory brainstem of the Mexican free-tailed bat, Tadarida brasiliensis. J. Comp. Neurol. 435, 78–88 (2001).
40
Z.-Q. Tang, L. O. Trussell, Serotonergic regulation of excitability of principal cells of the dorsal cochlear nucleus. J. Neurosci. 35, 4540–4551 (2015).
41
Z.-Q. Tang, L. O. Trussell, Serotonergic modulation of sensory representation in a central multisensory circuit is pathway specific. Cell Rep. 20, 1844–1854 (2017).
42
H. W. Steinbusch, Distribution of serotonin-immunoreactivity in the central nervous system of the rat-cell bodies and terminals. Neuroscience 6, 557–618 (1981).
43
M. M. Scott, K. C. Krueger, E. S. Deneris, A differentially autoregulated Pet-1 enhancer region is a critical target of the transcriptional cascade that governs serotonin neuron development. J. Neurosci. 25, 2628–2636 (2005).
44
D. Oertel, S. H. Wu, Morphology and physiology of cells in slice preparations of the dorsal cochlear nucleus of mice. J. Comp. Neurol. 283, 228–247 (1989).
45
B. N. Armbruster, X. Li, M. H. Pausch, S. Herlitze, B. L. Roth, Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand. Proc. Natl. Acad. Sci. U.S.A. 104, 5163–5168 (2007).
46
V. C. Torres Irizarry et al., Estrogen signaling in the dorsal raphe regulates binge-like drinking in mice. Transl. Psychiatry 14, 122 (2024).
47
S. Masri et al., Chemogenetic activation of cortical parvalbumin-positive interneurons reverses noise-induced impairments in gap detection. J. Neurosci. 41, 8848–8857 (2021).
48
M. Rezapour, M. Farrahizadeh, M. Akbari, Effectiveness of transcutaneous vagus nerve stimulation (tVNS) on salicylate-induced tinnitus. Neurosci. Lett. 822, 137639 (2024).
49
W. Wang et al., Neuroinflammation mediates noise-induced synaptic imbalance and tinnitus in rodent models. PLoS Biol. 17, e3000307 (2019).
50
F. Deng et al., Improved green and red GRAB sensors for monitoring spatiotemporal serotonin release in vivo. Nat. Methods 21, 692–702 (2024).
51
T.-W. Chen et al., Ultrasensitive fluorescent proteins for imaging neuronal activity. Nature 499, 295–300 (2013).
52
W. E. Allen et al., Thirst-associated preoptic neurons encode an aversive motivational drive. Science 357, 1149–1155 (2017).
53
L. Li et al., Dorsal raphe nucleus to anterior cingulate cortex 5-HTergic neural circuit modulates consolation and sociability. Elife 10, e67638 (2021).
54
A. Belmer, R. Depoortere, K. Beecher, A. Newman-Tancredi, S. E. Bartlett, Neural serotonergic circuits for controlling long-term voluntary alcohol consumption in mice. Mol. Psychiatry 27, 4599–4610 (2022).
55
M. A. Muniak, D. K. Ryugo, Tonotopic organization of vertical cells in the dorsal cochlear nucleus of the CBA/J mouse. J. Comp. Neurol. 522, 937–949 (2014).
56
J. Wan et al., A genetically encoded sensor for measuring serotonin dynamics. Nat. Neurosci. 24, 746–752 (2021).
57
J. Liu et al., Effects of salicylate on serotoninergic activities in rat inferior colliculus and auditory cortex. Hear. Res. 175, 45–53 (2003).
