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Intact-Brain Analyses Reveal Distinct Information Carried by SNc Dopamine Subcircuits
Open accessAbstract
Recent progress in understanding the diversity of midbrain dopamine neurons has highlighted the importance--and the challenges--of defining mammalian neuronal cell types. Although neurons may be best categorized using inclusive criteria spanning biophysical properties, wiring of inputs, wiring of outputs, and activity during behavior, linking all of these measurements to cell types within the intact brains of living mammals has been difficult. Here, using an array of intact-brain circuit interrogation tools, including CLARITY, COLM, optogenetics, viral tracing, and fiber photometry, we explore the diversity of dopamine neurons within the substantia nigra pars compacta (SNc). We identify two parallel nigrostriatal dopamine neuron subpopulations differing in biophysical properties, input wiring, output wiring to dorsomedial striatum (DMS) versus dorsolateral striatum (DLS), and natural activity patterns during free behavior. Our results reveal independently operating nigrostriatal information streams, with implications for understanding the logic of dopaminergic feedback circuits and the diversity of mammalian neuronal cell types.
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“Thus, the input-output architecture of the DR serotonin system differs from that of the locus coeruleus norepinephrine system with more homogeneous input and output (Schwarz et al., 2015), and resembles more closely those of the midbrain dopamine systems (Beier et al., 2015; Lerner et al., 2015), with biased input and segregated output.”
From Anatomically defined and functionally distinct dorsal raphe serotonin sub-systems (2018) · cites this paper as Lerner et al., 2015
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“Thus, a strong activation in response to the physical impact of an aversive stimulus in particularly sensitive neurons may supersede a depression reflecting the negative value, and this might appear as a categorical difference in aversive and motivational salience coding15,23,24,134.”
From Dopamine reward prediction-error signalling: A two-component response (2016) · cites this paper as [134]
In the citing paper
“Dopamine neurons in the lateral midbrain display greater burst activity in vivo28 and higher excitability in vitro29,30 than those in the medial midbrain, such as the ventral tegmental area (VTA), where canonical reward-processing dopamine neurons reside.”
From Dopamine dynamics as a regulatory mechanism for shifting between defensive and reward-seeking behaviors (2026) · cites this paper as [30]
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Cites
A neural substrate of prediction and reward
Schultz, W., Dayan, P., & Montague, P. R. (1997) · Science · doi:10.1126/science.275.5306.1593 · Cited by 9,388 · cited 2×
“Seminal early studies into the information encoded by midbrain DA neurons suggested that a key function of DA is to transmit reward prediction error signals (Mirenowicz and Schultz, 1996; Schultz et al., 1997; Waelti et al., 2001), a hypothesis concordant with temporal difference learning models (Montague et al.”
ResultUltrasensitive fluorescent proteins for imaging neuronal activity
Chen, T.-W., Wardill, T. J., Sun, Y., Pulver, S. R., Renninger, S. L., Baohan, A., Schreiter, E. R., Kerr, R. A., Orger, M. B., Jayaraman, V., et al. (2013) · Nature · doi:10.1038/nature12354 · Cited by 6,474 · cited 1×
“We expressed GCaMP6f (Chen et al., 2013) in DMS- or DLS-projecting SNc DA neurons by injecting CAV-cre into the DMS or the DLS, followed by injection of a cre-dependent GCaMP6f construct into the SNc.”
MethodLearning to predict by the methods of temporal differences
Sutton, R. S. (1988) · Machine Learning · doi:10.1007/bf00115009 · Cited by 5,148 · cited 2×
“…neurons suggested that a key function of DA is to transmit reward prediction error signals (Mirenowicz and Schultz, 1996; Schultz et al., 1997; Waelti et al., 2001), a hypothesis concordant with temporal difference learning models (Montague et al., 1996, 2004; Steinberg et al., 2013; Sutton, 1988).”
BackgroundDopamine in motivational control: rewarding, aversive, and alerting
Bromberg-Martin, E. S., Matsumoto, M., & Hikosaka, O. (2010) · Neuron · doi:10.1016/j.neuron.2010.11.022 · Cited by 2,396 · cited 4×
“…that the DA neurons, which increase their firing in response to these stimuli, may signal salience rather than value (Brischoux et al., 2009; Bromberg-Martin et al., 2010; Matsumoto and Hikosaka, 2009), though controversy on this point remains (Cohen et al., 2012; Fiorillo et al., 2013,…”
BackgroundInfluentialA framework for mesencephalic dopamine systems based on predictive Hebbian learning
Montague, P., Dayan, P., & Sejnowski, T. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-05-01936.1996 · Cited by 2,066 · cited 1×
“…neurons suggested that a key function of DA is to transmit reward prediction error signals (Mirenowicz and Schultz, 1996; Schultz et al., 1997; Waelti et al., 2001), a hypothesis concordant with temporal difference learning models (Montague et al., 1996, 2004; Steinberg et al., 2013; Sutton, 1988).”
Structural and molecular interrogation of intact biological systems
Chung, K., Wallace, J., Kim, S.-Y., Kalyanasundaram, S., Andalman, A. S., Davidson, T. J., Mirzabekov, J. J., Zalocusky, K. A., Mattis, J., Denisin, A. K., et al. (2013) · Nature · doi:10.1038/nature12107 · Cited by 2,008 · cited 6×
“We began by demonstrating that novel circuit-tracing and -recording methodologies can be effectively combined with whole-brain CLARITY/COLM imaging (Chung et al., 2013; Tomer et al., 2014) to provide a uniquely informative overview of richly defined cell types and their global connectivity motifs…”
BackgroundMethodInfluentialSelf-citationHaber, S. N., Fudge, J. L., & McFarland, N. R. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-06-02369.2000 · Cited by 1,610 · cited 1×
“This information notably enriches the ascending spiral model proposed by Haber et al. (2000), which could not make definitive statements about striatal inputs onto DAergic versus non-DAergic midbrain cells.”
BackgroundNatural neural projection dynamics underlying social behavior
Gunaydin, L. A., Grosenick, L., Finkelstein, J. C., Kauvar, I. V., Fenno, L. E., Adhikari, A., Lammel, S., Mirzabekov, J. J., Airan, R. D., Zalocusky, K. A., et al. (2014) · Cell · doi:10.1016/j.cell.2014.05.017 · Cited by 1,389 · cited 1×
“…monitored activity from projection-defined SNc DA neurons during behavior using fiber photometry, a method for collecting population intracellular [Ca2+] fluorescent signals from a genetically encoded Ca2+ indicator such as GCaMP through a single chronic fiber optic implant (Gunaydin et al., 2014).”
MethodTwo types of dopamine neuron distinctly convey positive and negative motivational signals
Matsumoto, M., & Hikosaka, O. (2009) · Nature · doi:10.1038/nature08028 · Cited by 1,378 · cited 5×
“Another study used recordings in awake monkeys to demonstrate a correlation between the depth at which a DA neuron was recorded along the electrode (indicating a more ventromedial location in the midbrain) and the likelihood that it would decrease rather than increase its firing in response to an aversive cue (Matsumo…”
BackgroundResultInfluentialNeuron-type-specific signals for reward and punishment in the ventral tegmental area
Cohen, J. Y., Haesler, S., Vong, L., Lowell, B. B., & Uchida, N. (2012) · Nature · doi:10.1038/nature10754 · Cited by 1,318
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Mapping neural circuits with CLARITY
Willard, A. M., & Gittis, A. H. (2015) · eLife · doi:10.7554/elife.11409 · Cited by 7
“At first it was thought that the neurons in the dopamine system were all quite similar, but over the past decade it has become clear that they exhibit a range of molecular, anatomical and functional properties (Lammel et al., 2008; Margolis et al., 2008; Lammel et al., 2011).”
BackgroundDopaminergic axons track somatic signaling in behaving micePreprint
Azcorra, M., Gaertner, Z. A., Davidson, C., Ramakrishnan, C., Fenno, L. E., Kim, Y. S., Deisseroth, K. A., Awatramani, R. B., & Dombeck, D. A. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.06.20.496872 · Cited by 7
Seiler, J. L., Zhuang, X., Nelson, A., & Lerner, T. N. (2024) · Experimental Neurology · doi:10.1016/j.expneurol.2024.114693 · Cited by 6
Stojanovic, S., Knowlton, C. J., Egger-Mackrodt, R., Mankel, J., Shin, J., Lammel, S., Canavier, C. C., & Roeper, J. (2025) · Journal of Neuroscience · doi:10.1523/jneurosci.0361-25.2025 · Cited by 6
“Lerner and colleagues found only minor intrinsic di ff erences in electrophysiological pro fi les (e.g., HCN current amplitudes) between DA SN neurons projecting to dorsomedial or dorsolateral striatum (DMS and DLS, respectively; Lerner et al., 2015).”
Carvalheiro, J., & Philiastides, M. G. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113589 · Cited by 11
Shifting GnRH Neuron Ensembles Underlie Successive Preovulatory Luteinizing Hormone Surges
Yeo, S., Han, S. Y., & Herbison, A. E. (2024) · Journal of Neuroscience · doi:10.1523/jneurosci.1383-24.2024 · Cited by 6
Broadband visual stimuli improve neuronal representation and sensory perception
Balla, E., Nabbefeld, G., Wiesbrock, C., Linde, J., Graff, S., Musall, S., & Kampa, B. M. (2025) · Nature Communications · doi:10.1038/s41467-025-58003-1 · Cited by 9
“To directly test the effect of orientation tuning and surround modulation on broadband responses of individual neurons, we performed additional experiments where we presented a set of narrow and broadband stimuli to awake 2NiellJ mice, expressing GCaMP6s in excitatory neurons (Fig.”
InfluentialOscillation/Coincidence-Detection Models of Reward-Related Timing in Corticostriatal Circuits
Yin, B., Shi, Z., Wang, Y., & Meck, W. H. (2022) · Timing & Time Perception · doi:10.1163/22134468-bja10057 · Cited by 7
Brandner, D. D., Retzlaff, C. L., Kocharian, A., Stieve, B. J., Mashal, M. A., Mermelstein, P. G., & Rothwell, P. E. (2022) · Addiction Biology · doi:10.1111/adb.13247 · Cited by 6
“The change in fluorescent signal (ΔF/F) was calculated within each session as described.(28) Each”
Adolescent neurostimulation of dopamine circuit reverses genetic deficits in frontal cortex function
Mastwal, S. S., Li, X., Stowell, R. D., Manion, M. T. C., Zhang, W., Kim, N., Yoon, K., Song, H., Ming, G., & Wang, K. H. (2023) · eLife · doi:10.7554/elife.87414 · Cited by 14
“…VTA stimulation led to prolonged frontal local field potential responses with high-frequency oscillations ( Mastwal et al., 2014 ), which is characteristic of increased dopaminergic signaling ( Gireesh and Plenz, 2008 ; Lewis and O’Donnell, 2000 ; Lohani et al., 2019 ; Wood et al., 2012 ).”
Cell type specificity for circuit output in the midbrain dopaminergic system
Blaess, S., & Krabbe, S. (2023) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2023.102811 · Cited by 6
“…studies analyzing monosynaptic inputs to mDA subtypes defined by their specific projection targets demonstrate that mDA neurons receive in general broad input from many brain areas with no clearly distinct relationship between projection target and monosynaptic input specificity [20,21,34 e 37].”
The Neuropsychology of Movement and Movement Disorders: Neuroanatomical and Cognitive Considerations
Haaland, K. Y., Dum, R. P., Mutha, P. K., Strick, P. L., & Tröster, A. I. (2017) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617717000698 · Cited by 7
Evolution of in vivo dopamine monitoring techniques
Yocky, A. G., & Covey, D. P. (2020) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2020.173078 · Cited by 8
SYNCHRONICITY: THE ROLE OF MIDBRAIN DOPAMINE IN GENERATING WHOLE BRAIN COHERENCE, A HYPOTHESISPreprint
Beeler, J. A., & Dreyer, J. K. (2018) · OSF Preprints (OSF Preprints) · doi:10.31219/osf.io/8qfp2 · Cited by 6
Campagner, D., Bhagat, J., Lopes, G., Calcaterra, L., Pouget, A., Almeida, A., Nguyen, T. T., Lo, C. H., Ryan, T. M., Cruz, B. D. O., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.07.31.664513 · Cited by 13
The Basal Ganglia and Mesencephalic Locomotor Region Connectivity Matrix
Morgenstern, N. A., & Esposito, M. S. (2023) · Current Neuropharmacology · doi:10.2174/1570159x21666230809112840 · Cited by 5
Yoshizawa, T., & Funahashi, M. (2024) · Neuroscience Research · doi:10.1016/j.neures.2024.11.002 · Cited by 5
Reddy, P., Prajapati, J. N., Chaterji, S., Varughese, A., Chaudhary, Y., Sathyamurthy, A., & Barik, A. (2024) · Pain · doi:10.1097/j.pain.0000000000003468 · Cited by 5
Altered thermal preference by preoptic estrogen receptor alpha neurons in postpartum females
Zhang, N., Yu, M., Zhao, Q., Feng, B. C., Deng, Y., Bean, J. C., Liu, Q., Eappen, B. P., He, Y., Conde, K., et al. (2025) · Molecular Metabolism · doi:10.1016/j.molmet.2025.102108 · Cited by 7
“To calculate D F/F, a least-squares linear fi t was applied to the 405 nm signal to align it to the 465 nm signal, producing a fi tted 405 nm signal that was used to normalize the 490 nm as follows: D F/F ¼ (465 nm signal (cid:5) fi tted 405 nm signal)/ fi tted 405 nm signal [108].”
A decision-space model explains context-specific decision-making
Beck, D. W., Heaton, C. N., Davila, L. D., Rakocevic, L. I., Drammis, S. M., Tyulmankov, D., Giri, A., Beck, S. U., Zhang, Q., Pokojovy, M., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-61466-x · Cited by 5
Fluorescent boost for voltage sensors
Gradinaru, V., & Flytzanis, N. C. (2016) · Nature · doi:10.1038/529469a · Cited by 5
Correcting for the hemoglobin absorption artifact in fiber photometry data
Zhang, R., & Kim, C. K. (2022) · Cell Reports Methods · doi:10.1016/j.crmeth.2022.100257 · Cited by 5
Distinct cortico-striatal compartments drive competition between adaptive and automatized behavior
Barnett, W. H., Kuznetsov, A. S., & Lapish, C. C. (2023) · PLoS ONE · doi:10.1371/journal.pone.0279841 · Cited by 6
A novel small molecule, AS1, reverses the negative hedonic valence of noxious stimuli
Esancy, K., Conceicao, L. L., Curtright, A., Tran, T., Condon, L. F., Lecamp, B., & Dhaka, A. (2023) · BMC Biology · doi:10.1186/s12915-023-01573-7 · Cited by 5
Rethinking dopamine‐guided action sequence learning
Song, M. R., & Lee, S. W. (2024) · European Journal of Neuroscience · doi:10.1111/ejn.16426 · Cited by 6
“…to the VS most closely resemble the RPE, while those projecting to the DMS or the DLS exhibit a lesser degree of similarity, with the latter showing the least resemblance to the RPE (Amo et al., 2022; Lee et al., 2019; Lerner et al., 2015; Menegas et al., 2017; Tsutsui-Kimura et al., 2020).”
BackgroundZhao, B., Liang, L., Li, J., Schaefke, B., Wang, L., & Tseng, Y.-T. (2024) · Neurobiology of Disease · doi:10.1016/j.nbd.2024.106649 · Cited by 5
“Consequently, the signal before struggling or licking may not be centered around zero (Lerner et al., 2015).”
Genetic tools to study complexity of striatal function
Ciriachi, C., Svane‐Petersen, D., & Rickhag, M. (2019) · Journal of Neuroscience Research · doi:10.1002/jnr.24479 · Cited by 5
“The authors propose that parallel projections, originating from distinct subdomains within the striatum, may con‐ vey different streams of information and be involved in different behavioral paradigms (Lerner et al., 2015).”
BackgroundInfluentialKhiarak, M. N., Sasagawa, K., Tokuda, T., et al. (2018) · IEEE International New Circuits and Systems Conference (NEWCAS) · doi:10.1109/newcas.2018.8585682 · Cited by 5
“Unlike conventional brain imaging approaches, fluorescence measurement utilizing and implantable optical fiber, a technique known as fiber photometry, gives access to single cells activity within deep brain structures [1].”
BackgroundKılıç, K. D. (2023) · Advances in computational intelligence and robotics book series · doi:10.4018/978-1-6684-9814-9.ch008 · Cited by 5
Miniaturized head-mounted device for whole cortex mesoscale imaging in freely behaving micePreprint
Rynes, M. L., Surinach, D. A., Linn, S., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.05.25.114892 · Cited by 5
Reichenbach, A., Clarke, R., Stark, R., Lockie, S. H., Méquinion, M., Reed, F. M., Rawlinson, S., Dempsey, H., Sepehrizadeh, T., DeVeer, M., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.03.22.436393 · Cited by 5
A Dynamic Affective Core to bind the Contents, Context, and Value of Conscious ExperiencePreprint
Kishida, K. T., & Sands, L. P. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.05.20.444839 · Cited by 5
“This may not be surprising given the significant heterogeneity in the molecular, cellular, and neuroanatomical characteristics that differentiate dopamine neurons (Watabe-Uchida, et al., 2012; Lammel et al., 2014; Beier et al., 2015; Lerner et al 2015; Gantz et al., 2018).”
BackgroundAvvisati, R., Kaufmann, A.-K., Young, C. J., Portlock, G. E., Cancemi, S., Costa, R. P., Magill, P. J., & Dodson, P. D. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.07.18.500429 · Cited by 5
“Given the different roles ascribed to the ventral tegmental area (VTA) and the substantia nigra pars compacta (SNc), one might expect that neurons in these regions would encode the task differently (Collins and Saunders, 2020; Cox and Witten, 2019; Lerner et al., 2021).”
BackgroundOverlapping representations of food and social stimuli in VTA dopamine neuronsPreprint
Willmore, L., Minerva, A. R., Engelhard, B., Murugan, M., McMannon, B., Oak, N., Thiberge, S. Y., Peña, C. J., & Witten, I. B. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.05.17.541104 · Cited by 5
A septo-hypothalamic-medullary circuit directs stress-induced analgesiaPreprint
Shah, D. P., Sharma, P. R., Agarwal, R., & Barik, A. (2024) · eLife · doi:10.7554/elife.96724 · Cited by 6
Dorsal hippocampus mediates light–tone associations in male micePreprint
Pinho, J., Ramon‐Duaso, C., Manzanares-Sierra, I., & Busquets-García, A. (2025) · eLife · doi:10.7554/elife.105863 · Cited by 6
“This procedure is the same as described in previous works ( Lerner et al., 2015 ).”
Sulaman, B. A., Chen, E., Crane, A. M., Lee, S.-J., Rothschild, G., & Eban-Rothschild, A. (2025) · Science Advances · doi:10.1126/sciadv.adw7427 · Cited by 4
Ocana-Santero, G., Packer, A. M., Sharp, T., et al. (2024) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.3c00725 · Cited by 4
Gao, L., Huang, S., Li, X., et al. (2024) · Advanced Materials Interfaces · doi:10.1002/admi.202400767 · Cited by 4
Bingul, A., Merlin, S., Carrive, P., Killcross, S., & Furlong, T. M. (2022) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2022.107657 · Cited by 3
Kokhan, V. S., Chaprov, K., Абаимов, Д. А., Nesterov, M. S., & Pikalov, V. A. (2024) · Life Sciences in Space Research · doi:10.1016/j.lssr.2024.08.005 · Cited by 4
Conde-Berriozabal, S., Sitjà‐Roqueta, L., García-García, E., García-Gilabert, L., Sancho‐Balsells, A., Fernández-García, S., Rodríguez-Urgellés, E., Giralt, A., Castañé, A., Rodríguez, M. J., et al. (2024) · Experimental Neurology · doi:10.1016/j.expneurol.2024.114991 · Cited by 4
“Notably, both direct and indirect pathways project to their specific output nuclei with segregated mediolateral connections (Lee et al., 2020; Lerner et al., 2015).”
Policy Complexity Suppresses Dopamine Responses
Gershman, S. J., & Lak, A. (2025) · Journal of Neuroscience · doi:10.1523/jneurosci.1756-24.2024 · Cited by 5
Striatal astrocytes modulate behavioral flexibility and whole-body metabolism in mice
Montalban, E., Ansoult, A., Chao, D. H. M., Pham, C., Franco, C., Contini, A., Castel, J., Hassouna, R., Hardonk, M. H., Petitbon, A., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-60968-y · Cited by 6
The Rostromedial Tegmental Nucleus: Connections With the Basal Ganglia
Zahm, D. S. (2016) · Handbook of behavioral neuroscience · doi:10.1016/b978-0-12-802206-1.00026-x · Cited by 4
Hyde, J., & García‐Rill, E. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-817992-5.00006-4 · Cited by 4
Sex Differences in the Role of Neurexin 3α in Zoster Associated Pain
Kramer, P. R., Umorin, M., Hornung, R. S., Benson, M. D., & Kinchington, P. R. (2022) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2022.915797 · Cited by 4
“Fluorescence Data Analysis The neuronal signal was calculated using a least-squares regression line between the 465 nm fluorescence signal (dependent variable) and the 405 nm fluorescence signal (independent variable) (Lerner et al., 2015).”
MethodBaird, T. R., Karin, K. N., Marsh, S. A., Carroll, F. I., Contreras, J. M. D. L. M., Negus, S. S., & Eltit, J. M. (2023) · Psychopharmacology · doi:10.1007/s00213-023-06340-8 · Cited by 4
“The emitted signals were recovered using two dual-analog lockin amplifiers (one per channel) (Lerner et al. 2015).”
BackgroundMethodThe Contribution of the Amygdala to Reward-Related Learning and Extinction
Chesworth, R., & Corbit, L. H. (2017) · InTech eBooks · doi:10.5772/67831 · Cited by 4
“Evidence for this comes from the demonstration that unilateral lesions of the CeA coupled with dopamine depletion in the DLS in the opposing hemisphere impairs conditioned orienting responses for food pellets, while leaving food cup approach behaviour intact [88].”
BackgroundInfluentialGong, W., Ni, J., Yu, L.-F., Wang, L., & Huang, Z. (2020) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2019.107156 · Cited by 4
Shi, R., Schroeder, G. M., & Nimarko, A. F. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.0753-16.2016 · Cited by 4
“one could investigate changes in the amplitude of a quantal response using optogenetic stimulation in the presence of strontium (Lerner et al., 2015).”
BackgroundLimbrick‐Oldfield, E. H., Leech, R., Wise, R. G., & Ungless, M. A. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.14288 · Cited by 4
“Indeed, SNC dopamine neurons in particular, sit within a largely inhibitory network of extrinsic inputs (Lerner et al., 2015; Watabe- Uchida, Zhu, Ogawa, Vamanrao, & Uchida, 2012) and receive proportionally more synaptic inhibition than excitation (Bayer & Pickel, 1991; Bolam & Smith, 1990; Henny…”
BackgroundPeters, K. Z., Young, A. M. J., & McCutcheon, J. E. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.15108 · Cited by 3
“The calcium-modulated signal was corrected for artefacts and bleaching using the isosbestic signal as a reference (Lerner et al., 2015).”
MethodThe Brain, Explained: A Comprehensive Theory of Brain FunctionPreprint
Rappoport, A. (2018) · Preprints.org · doi:10.20944/preprints201805.0137.v1 · Cited by 4
Firing patterns of serotonin neurons underlying cognitive flexibilityPreprint
Matias, S., Lottem, E., Dugué, G. P., & Mainen, Z. F. (2016) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/059758 · Cited by 5
Mesoscale microscopy for micromammals: image analysis tools for understanding the rodent brainPreprint
Tyson, A. L., & Margrie, T. W. (2021) · arXiv (Cornell University) · doi:10.48550/arxiv.2102.11812 · Cited by 5
“LSFM has been extensively applied to image whole mouse brains (Dodt et al., 2007; Lerner et al., 2015; Renier et al., 2016, 2014; Susaki et al., 2014; Tomer et al., 2014).”
MethodA role for MCH neuron firing in hippocampal plasticity and learningPreprint
Harris, J. J., Concetti, C., Peleg‐Raibstein, D., & Burdakov, D. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.12.01.518339 · Cited by 4
“To produce the plotted % ΔF/F values, the raw 405 -nm–excited signal was fitted to the 465-nm–excited signal, then the % ΔF/F time series was calculated for each session as [100*(465 signal – fitted 405 signal)/fitted 405 signal], based on Lerner et al. (2015).”
MethodHuman Substantia Nigra Neurons Encode Reward ExpectationsPreprint
Imtiaz, Z., Kato, A., Kopell, B. H., Qasim, S. E., Davis, A. N., Martinez, L. N., Heflin, M., Kulkarni, K. R., Morsi, A., Gu, X., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.10.593406 · Cited by 4
Roles of feedback and feed-forward networks of dopamine subsystems: insights fromDrosophilastudiesPreprint
Davidson, A. M., & Hige, T. (2024) · Learning & Memory · doi:10.1101/lm.053807.123 · Cited by 4
“…that broadcasts reward signals, it has become clear that they consist of functionally diverse groups, with some of them mediating aversive stimuli (Matsumoto and Hikosaka 2009; Lerner et al. 2015; Menegas et al. 2018; de Jong et al. 2019; Yuan et al. 2019).”
BackgroundGaertner, Z. A., Oram, C., Schneeweis, A. K., Schonfeld, E., Bolduc, C., Chen, C., Dombeck, D. A., Parisiadou, L., Poulin, J. F., & Awatramani, R. B. (2024) · eLife · doi:10.7554/elife.101035.1 · Cited by 5
FiPhoPHA—A Fiber Photometry Python Package for Post Hoc Analysis
Drakopoulos, V., Reichenbach, A., Stark, R., et al. (2025) · eNeuro · doi:10.1523/eneuro.0221-25.2025 · Cited by 4
“However, these approaches are inadvertently biased based on user-de fi ned time periods for analysis with potential unmet assumptions about data distribution.”
Yan, G., Amita, H., Nonomura, S., Inoue, K., Schultz, W., & Takada, M. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2426861122 · Cited by 3
“Third, diverse subsets of mid-brain DA neurons may transmit distinct signals to different striatal territories, similar to the dissociation between the DMS and the DLS in rodents ( 58 , 59 ).”
Sköld, J., Lazzarino, G. P., Nett, M., Wiskerke, J., & Engblom, D. (2025) · iScience · doi:10.1016/j.isci.2025.112456 · Cited by 3
“34,35 The raw 465nm and 405nm signals were down-sampled to 100 Hz.”
Fudge, J. L., Kelly, E. A., & Mahoui, I. (2025) · Genomic psychiatry : · doi:10.61373/gp025i.0038 · Cited by 3
Hohorst, A. A., Tanner, M. K., Han, R., Korth, K. M., Westerman, J. D., Mendoza, C. S., Dryden, M. Q., Alverez, L., Abdul, R. A., Loetz, E. C., et al. (2025) · Biology of Sex Differences · doi:10.1186/s13293-025-00722-7 · Cited by 3
“DLS-projecting SN neurons branch and project to other regions [40]; therefore, terminal mCherry immunoreactivity was quantified in regions implicated in fear extinction with densitometry in rats injected with hM4Di. mCherry expression did not vary by estrous phase at the time of extinction (F…”
Miller, C. N., Li, Y., Beier, K. T., & Aoto, J. N. (2025) · Nature Communications · doi:10.1038/s41467-025-60512-y · Cited by 4
“Fiber photometry recordings were conducted using previously described equipment 113 .”
Genetic therapies for neurological diseases
Rahim, A. A., Kurian, M. A., Zhou, H., Ferguson, R., Tabrizi, S. J., Lignani, G., Aquilina, K., & Waddington, S. N. (2025) · Pharmacological Reviews · doi:10.1016/j.pharmr.2025.100093 · Cited by 4
“These include, among many, identification of 2 distinct dopaminergic pathway circuits, 61 the mechanism by which visual perception drives adaptive threat response, 62 the integration of predatory motor function by the central nucleus of the amygdala, 63 pre-frontal cortex control of reward-seeking…”
The distinct subpopulations in parafascicular thalamic nucleus encoding innate emotional valence
Chen, P.-P., Wang, J.-G., Teng, S.-W., Yao, Z.-X., Che, Y.-Y., Chen, X.-L., Gao, S.-B., Chi, R.-F., Zhang, D., & Chen, Z.-Y. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116482 · Cited by 2
Striatum-wide dopamine encodes trajectory errors separated from value
Brown, E. H., Zi, Y., Vu, M.-A. T., Bouabid, S., Lindsey, J. W., Godfrey-Nwachukwu, C., Attarwala, A., Litwin-Kumar, A., DePasquale, B., & Howe, M. W. (2026) · Nature · doi:10.1038/s41586-025-10083-1 · Cited by 4
Neurovascular coupling in the basolateral amygdala modulates negative emotions
Ruan, J., Quan, X., Xie, H., Zhang, Y., Zhang, D., Wang, W., Zhao, B., Lu, D., Niu, Y., Diao, M., et al. (2026) · Cell Research · doi:10.1038/s41422-026-01256-2 · Cited by 3
A nigroincertal projection mediates aversion and enhances coping responses to potential threat
Ho, P., Hsiao, F. S. H., Chiu, S., et al. (2023) · The FASEB Journal · doi:10.1096/fj.202201989rr · Cited by 3
Huang, X., Wang, S., Chen, Z., Qu, W., Song, L., Hu, Z., Xi, Y., Yang, Y., Hong, W.-H., Lin, S., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115865 · Cited by 5
Christensen, M. E., Nørr, S. E., Gether, U., & Rickhag, M. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.11.035 · Cited by 3
Young, P. A., Waller, O., Ball, K., Williams, C. C., & Nashmi, R. (2024) · Neuroscience · doi:10.1016/j.neuroscience.2024.05.025 · Cited by 3
“Another explanation could be that SNc DA neurons are heterogeneous in their gene expression and function (Lerner et al., 2015; Estakhr et al., 2017; Azcorra et al., 2023) and the positioning of our fi ber optic implants stimulated a subpopulation that does not affect the vigour of the movement,…”
BackgroundLeveraging Fiber Photometry to Decipher Neural Circuits Underlying Anxiety in Mice
Abdennebi, S. R., Touihri, N. E. H., Corruble, E., David, D. J. P., & Mendez‐David, I. (2025) · Fundamental and Clinical Pharmacology · doi:10.1111/fcp.70043 · Cited by 2
“To isolate the true calcium-dependent signal, a linear regression is performed where the calcium-sensitive fluorescence trace is regressed onto the isosbestic reference [25].”
A Hitchhiker’s Guide to the Selection of Viral Vectors for Optogenetic Studies
Thompson, K. R., & Towne, C. L. (2017) · Neuromethods · doi:10.1007/978-1-4939-7417-7_1 · Cited by 4
Petese, A., Fries, F. L., Broske, B., Stumm, R. K., & Blaess, S. (2022) · eNeuro · doi:10.1523/eneuro.0052-22.2022 · Cited by 3
“Our observation that medial SNc neurons project to the DMS is consistent with the study of Lerner et al. (2015), which used retrograde viral tracing to show that DLS-projecting SNc–mDA neurons are located in the lateral SNc, and DMS-projecting ones in the medial SNc.”
BackgroundResultInfluentialAnimal Models Are Valid to Uncover Disease Mechanisms
Wurst, W. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1006013 · Cited by 3
The biological and behavioral computations that influence dopamine responses
Stauffer, W. R. (2018) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2018.02.005 · Cited by 3
Khiarak, M. N., Gagnon-Turcotte, G., Martianova, E., et al. (2018) · Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) · doi:10.1109/embc.2018.8512653 · Cited by 3
Monitoring Neural Activity During Exposure to Drugs of Abuse With In Vivo Fiber PhotometryPreprint
Rinker, J. A., Gioia, D. A., Braunscheidel, K. M., Wayman, W. N., Hoffman, M., Passarella, L. S., Calipari, E. S., Mulholland, P. J., & Woodward, J. J. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/487546 · Cited by 3
“In Vivo Fiber Photometry Imaging Data were acquired using custom-built imaging equipment based on that described by the Deisseroth lab (Lerner et al, 2015) with modifications.”
BackgroundMethodCui, L., Tang, S., Zhao, K., Pan, J., Zhang, Z., Si, B., & Xu, N.-L. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.11.16.468594 · Cited by 3
“The 410-nm reference trace was scaled to best fit the 470-nm signals using least-squares regression [14].”
BackgroundMethodKahan, A., Kassraian, P., Altermatt, M., & Gradinaru, V. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4052008 · Cited by 3
Neuron glial antigen 2 in the striatum of parkinsonian rats presenting L-DOPA induced dyskinesiaPreprint
Nascimento, G. C., Bortolanza, M., & Bel, E. D. (2021) · doi:10.22541/au.162143726.67718314/v1 · Cited by 3
What is dopamine doing in model-based reinforcement learning?Preprint
Akam, T., & Walton, M. E. (2020) · PsyArXiv (OSF Preprints) · doi:10.31234/osf.io/z2fmw · Cited by 4
Exploratory rearing is governed by hypothalamic MCH cells according to the locus coeruleusPreprint
Concetti, C., Viskaitis, P., Grujic, N., Duss, S. N., Privitera, M., Bohacek, J., Peleg‐Raibstein, D., & Burdakov, D. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.07.19.549648 · Cited by 3
A computational principle of habit formationPreprint
Lakshminarasimhan, K. J. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.12.618033 · Cited by 3
“Third, the two regions receive inputs from different sets of dopaminergic neurons in the substantia nigra that have qualitatively different response properties (Lerner et al., 2015; Tsutsui-Kimura et al., 2020).”
BackgroundSystem-wide dissociation of reward and aversive dopaminergic signalsPreprint
Bouchard, S.-J., Boutin, J., Lévesque, M., & Breton‐Provencher, V. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.27.656467 · Cited by 3
“Similarly, broad dopamine release in response to uncued reward and reward expectation has been reported in recordings across various basal ganglia subregions 18,20,22,24,28,49–51 .”
Chen, R., Xie, X., Gangal, H., Wang, X., & Wang, J. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.13.699373 · Cited by 2
Tsuruga, R., Tajika, Y., Minami, M., & Tsutsui-Kimura, I. (2026) · Communications Biology · doi:10.1038/s42003-026-10485-5 · Cited by 2
“Dopamine neurons in the lateral midbrain display greater burst activity in vivo 28 and higher excitability in vitro 29,30 than those in the medial midbrain, such as the ventral tegmental area (VTA), where canonical reward-processing dopamine neurons reside.”
Lewis, A. F., Bohnenkamp, R., Myers, M., den Ouden, D., Fritz, S. L., & Stewart, J. C. (2024) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2024.107930 · Cited by 4
Lovinger, D. M. (2025) · Alcohol · doi:10.1016/j.alcohol.2025.05.005 · Cited by 3
Sansalone, L., Twedell, E. L., Evans, R. C., Boronat-García, A., Zhang, R., & Khaliq, Z. M. (2025) · Nature Communications · doi:10.1038/s41467-025-63132-8 · Cited by 3
Cui, C., Yao, Y., Shi, Y., Lei, J., Ren, K., Wan, K., Li, T., Luo, G., Xu, Q., Li, M., et al. (2025) · PLoS Biology · doi:10.1371/journal.pbio.3003435 · Cited by 2
“Recent evidence suggested that SNc, as a part of the basal ganglia, plays a crucial role in processing and transmitting sensory information through its DA neurons [29,43].”
Cheng, Q., Liu, W., Li, Y., Xu, S., Wei, C., Zheng, Q., Wu, M., Han, J., Liu, Z., Ren, W., et al. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2509072122 · Cited by 2
“Additionally, SNc neurons, distinct from VTA neurons ( 14 , 18 ), may mediate action reinforcement in contrast to VTA’s role in reward prediction ( 19 ).”
Hernández, G., Zhao, J., Niu, Z., MacGowan, D., Capolicchio, T., Song, A., Gul, S., Moiz, A., Mahmud, A., Herrera, I., et al. (2025) · Communications Biology · doi:10.1038/s42003-025-09239-6 · Cited by 2
Sustained activity of human substantia nigra neurons reflect prior rewards
Imtiaz, Z., Kato, A., Kopell, B. H., Qasim, S. E., Davis, A. N., Martinez, L. N., Heflin, M., Kulkarni, K., Morsi, A., Charney, A. W., et al. (2026) · iScience · doi:10.1016/j.isci.2026.115458 · Cited by 2
“For example, dopaminergic neurons in rodent SN and VTA are capable of reflecting positive, negative RPEs or unsigned salience, 45–49 with differences in the representation of RPE in SN and VTA 50 ; our results show weak evidence in support of this heterogeneity in the human nigra.”
Ji, Y., Li, S., Zhang, J., Xu, X., Yin, C., Niu, M., Liu, D., Jiang, Y., 牛勇, Liu, S., et al. (2026) · Advanced Science · doi:10.1002/advs.202519913 · Cited by 2
Kim, H., Xu, C., Washington, C., Shi, C., Lowman, M., & Kebschull, J. M. (2026) · Neuron · doi:10.1016/j.neuron.2026.05.005 · Cited by 6
Pascoli, V., Python, L., Hiver, A., van Zessen, R., Chaudun, F., Hinz, J., Flakowski, J., Girard, B. J. T., Reva, M., Bellone, C., et al. (2026) · Nature Neuroscience · doi:10.1038/s41593-026-02331-y · Cited by 2
“RZ5P) to determine contributions from 470-nm and 405-nm excitation sources 75 .”
Metadata
- Authors
- Lerner, T. N., Shilyansky, C., Davidson, T. J., Evans, K. E., Beier, K. T., Zalocusky, K. A., Crow, A. K., Malenka, R. C., Luo, L., Tomer, R., & Deisseroth, K.
- Affiliations
- Stanford University (US)
- Stanford Medicine (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Deisseroth, Karl
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 162
- Issue
- 3
- Pages
- 635-647
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4790813
- OpenAlex
- W1875506666
- Cited by
- 794
- References
- 55
- Citations by year
- 2026: 52 · 2025: 90 · 2024: 87 · 2023: 77 · 2022: 85 · 2021: 77 · 2020: 70 · 2019: 71 · 2018: 70 · 2017: 51 · 2016: 51 · 2015: 13
- FWCI
- 28.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- H. L. Snyder Medical Foundation
- National Institutes of Health (5f31mh105151-02, 1f32mh105053-01)
- Defense Advanced Research Projects Agency
- National Institute of Mental Health (1F31MH105151-01, F32 MH105053, 1F32MH105053-01, P50MH086403, F31 MH105151)
- National Institute on Drug Abuse (F32DA038913, R37DA035377)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
- Keywords
- substantia nigra pars compacta, dopaminergic neurons, neuronal cell types, nigrostriatal pathway, dorsomedial striatum, dorsolateral striatum, striatal output, neuronal heterogeneity, clarity, optogenetics, viral tracing, fiber photometry
- MeSH terms
- Animals, Brain Mapping, Dopamine, Mice, Inbred C57BL, Neural Pathways, Neurons, Reward, Shock, Substantia Nigra, Mice
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