Skip to main content

Modeling Serotonin’s Contributions to Basal Ganglia Dynamics

  • Chapter
  • First Online:
Computational Neuroscience Models of the Basal Ganglia

Abstract

In addition to dopaminergic input, serotonergic (5-HT) fibers also widely arborize through the basal ganglia circuits and strongly control their dynamics. Although empirical studies show that 5-HT plays many functional roles in risk-based decision making, reward, and punishment learning, prior computational models mostly focus on its role in behavioral inhibition or timescale of prediction. This chapter presents an extended reinforcement learning (RL)-based model of DA and 5-HT function in the BG, which reconciles some of the diverse roles of 5-HT. The model uses the concept of utility function—a weighted sum of the traditional value function expressing the expected sum of the rewards, and a risk function expressing the variance observed in reward outcomes. Serotonin is represented by a weight parameter, used in this combination of value and risk functions, while the neuromodulator dopamine (DA) is represented as reward prediction error as in the classical models. Consistent with this abstract model, a network model is also presented in which medium spiny neurons (MSN) co-expressing both D1 and D2 receptors (D1R–D2R) is suggested to compute risk, while those expressing only D1 receptors are suggested to compute value. This BG model includes nuclei such as striatum, Globus Pallidus externa, Globus Pallidus interna, and subthalamic nuclei. DA and 5-HT are modeled to affect both the direct pathway (DP) and the indirect pathway (IP) composing of D1R, D2R, D1R–D2R projections differentially. Both abstract and network models are applied to data from different experimental paradigms used to study the role of 5-HT: (1) risk-sensitive decision making, where 5-HT controls the risk sensitivity; (2) temporal reward prediction, where 5-HT controls timescale of reward prediction, and (3) reward–punishment sensitivity, where punishment prediction error depends on 5-HT levels. Both the extended RL model (Balasubramani, Chakravarthy, Ravindran, & Moustafa, in Front Comput Neurosci 8:47, 2014; Balasubramani, Ravindran, & Chakravarthy, in Understanding the role of serotonin in basal ganglia through a unified model, 2012) along with their network correlates (Balasubramani, Chakravarthy, Ravindran, & Moustafa, in Front Comput Neurosci 9:76, 2015; Balasubramani, Chakravarthy, Ali, Ravindran, & Moustafa, in PLoS ONE 10(6):e0127542, 2015) successfully explain the three diverse roles of 5-HT in a single framework.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abbott, P. D. a. L. F. (2001). Theoretical neuroscience: Computational and mathematical modeling of neural systems. Cambridge, Massachusetts, London, England: The MIT Press.

    Google Scholar 

  • Aghajanian, G. K., & Marek, G. J. (2000). Serotonin model of schizophrenia: Emerging role of glutamate mechanisms. Brain Research Reviews, 31(2), 302–312.

    Article  Google Scholar 

  • Albin, R. L. (1998). Fuch’s corneal dystrophy in a patient with mitochondrial DNA mutations. Journal of Medical Genetics, 35(3), 258–259.

    Article  Google Scholar 

  • Albin, R. L., Young, A. B., & Penney, J. B. (1989). The functional anatomy of basal ganglia disorders. Trends in Neurosciences, 12(10), 366–375.

    Article  Google Scholar 

  • Alex, K. D., & Pehek, E. A. (2007). Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission. Pharmacology & Therapeutics, 113(2), 296–320. https://doi.org/10.1016/j.pharmthera.2006.08.004.

    Article  Google Scholar 

  • Allen, A. T., Maher, K. N., Wani, K. A., Betts, K. E., & Chase, D. L. (2011). Coexpressed D1-and D2-like dopamine receptors antagonistically modulate acetylcholine release in Caenorhabditis elegans. Genetics, 188(3), 579–590.

    Article  Google Scholar 

  • Amemori, K., Gibb, L. G., & Graybiel, A. M. (2011). Shifting responsibly: The importance of striatal modularity to reinforcement learning in uncertain environments. Frontiers in Human Neuroscience, 5, 47. https://doi.org/10.3389/fnhum.2011.00047.

    Article  Google Scholar 

  • Angiolillo, P. J., & Vanderkooi, J. M. (1996). Hydrogen atoms are produced when tryptophan within a protein is irradiated with ultraviolet light. Photochemistry and Photobiology, 64(3), 492–495.

    Article  Google Scholar 

  • Araki, K. Y., Sims, J. R., & Bhide, P. G. (2007). Dopamine receptor mRNA and protein expression in the mouse corpus striatum and cerebral cortex during pre-and postnatal development. Brain Research, 1156, 31–45.

    Article  Google Scholar 

  • Ashby, F. G., Turner, B. O., & Horvitz, J. C. (2010). Cortical and basal ganglia contributions to habit learning and automaticity. Trends in Cognitive Sciences, 14(5), 208–215.

    Article  Google Scholar 

  • Aston-Jones, G., & Cohen, J. D. (2005). An integrative theory of locus coeruleus-norepinephrine function: Adaptive gain and optimal performance. Annual Review of Neuroscience, 28, 403–450.

    Article  Google Scholar 

  • Azmitia, E. C. (1999). Serotonin neurons, neuroplasticity, and homeostasis of neural tissue. Neuropsychopharmacology, 21(2 Suppl), 33S–45S. https://doi.org/10.1016/S0893-133X(99)00022-6.

    Article  Google Scholar 

  • Azmitia, E. C. (2001). Modern views on an ancient chemical: Serotonin effects on cell proliferation, maturation, and apoptosis. Brain Research Bulletin, 56(5), 413–424.

    Article  Google Scholar 

  • Balasubramani, P. P., Chakravarthy, S., Ravindran, B., & Moustafa, A. A. (2014). An extended reinforcement learning model of basal ganglia to understand the contributions of serotonin and dopamine in risk-based decision making, reward prediction, and punishment learning. Frontiers in Computational Neuroscience, 8, 47.

    Article  Google Scholar 

  • Balasubramani, P. P., Chakravarthy, S., Ravindran, B., & Moustafa, A. A. (2015a). A network model of basal ganglia for understanding the roles of dopamine and serotonin in reward-punishment-risk based decision making. Name. Frontiers in Computational Neuroscience, 9, 76.

    Google Scholar 

  • Balasubramani, P. P., Chakravarthy, V. S., Ali, M., Ravindran, B., & Moustafa, A. A. (2015b). Identifying the Basal Ganglia network model markers for medication-induced impulsivity in Parkinson’s Disease patients. PLoS ONE, 10(6), e0127542.

    Article  Google Scholar 

  • Balasubramani, P. P., Ravindran, B., & Chakravarthy, S. (2012). Understanding the role of serotonin in basal ganglia through a unified model. Paper presented at the International Conference on Artificial Neural Networks, Lausanne, Switzerland.

    Google Scholar 

  • Bar-Gad, I., & Bergman, H. (2001). Stepping out of the box: Information processing in the neural networks of the basal ganglia. Current Opinion in Neurobiology, 11(6), 689–695.

    Article  Google Scholar 

  • Bell, C. (2001). Tryptophan depletion and its implications for psychiatry. The British Journal of Psychiatry, 178(5), 399–405. https://doi.org/10.1192/bjp.178.5.399.

    Article  Google Scholar 

  • Bell, D. E. (1995). Risk, return and utility. Management Science, 41, 23–30.

    Article  MATH  Google Scholar 

  • Belujon, P., Bezard, E., Taupignon, A., Bioulac, B., & Benazzouz, A. (2007). Noradrenergic modulation of subthalamic nucleus activity: Behavioral and electrophysiological evidence in intact and 6-hydroxydopamine-lesioned rats. The Journal of Neuroscience, 27(36), 9595–9606.

    Article  Google Scholar 

  • Bertler, A., & Rosengren, E. (1966). Possible role of brain dopamine. Pharmacological Reviews, 18(1), 769–773.

    Google Scholar 

  • Bertran-Gonzalez, J., Bosch, C., Maroteaux, M., Matamales, M., Herve, D., Valjent, E., et al. (2008). Opposing patterns of signaling activation in dopamine D1 and D2 receptor-expressing striatal neurons in response to cocaine and haloperidol. Journal of Neuroscience, 28(22), 5671–5685. https://doi.org/10.1523/JNEUROSCI.1039-08.2008.

    Article  Google Scholar 

  • Bertran-Gonzalez, J., Hervé, D., Girault, J.-A., & Valjent, E. (2010). What is the degree of segregation between striatonigral and striatopallidal projections? Front Neuroanat, 4.

    Google Scholar 

  • Boureau, Y. L., & Dayan, P. (2011). Opponency revisited: Competition and cooperation between dopamine and serotonin. Neuropsychopharmacology, 36(1), 74–97. https://doi.org/10.1038/npp.2010.151.

    Article  Google Scholar 

  • Buhot, M.-C. (1997). Serotonin receptors in cognitive behaviors. Current Opinion in Neurobiology, 7(2), 243–254.

    Article  Google Scholar 

  • Calabresi, P., Maj, R., Pisani, A., Mercuri, N. B., & Bernardi, G. (1992). Long-term synaptic depression in the striatum: Physiological and pharmacological characterization. Journal of Neuroscience, 12(11), 4224–4233.

    Google Scholar 

  • Calabresi, P., Picconi, B., Tozzi, A., Ghiglieri, V., & Di Filippo, M. (2014). Direct and indirect pathways of basal ganglia: A critical reappraisal. Nature Neuroscience, 17(8), 1022–1030.

    Article  Google Scholar 

  • Chakravarthy, V. S., & Balasubramani, P. P. (2013). Basal Ganglia System as an engine for exploration. In J. R. Jaeger D. (Ed.), Encyclopedia of Computational Neuroscience. Berlin Heidelberg: SpringerReference (http://www.springerreference.com/). Springer-Verlag.

  • Chakravarthy, V. S., & Balasubramani, P. P. (2014). Basal Ganglia System as an engine for exploration. Berlin Heidelberg: SpringerReference (http://www.springerreference.com/). Springer-Verlag.

  • Chakravarthy, V. S., Joseph, D., & Bapi, R. S. (2010). What do the basal ganglia do? A modeling perspective. Biological Cybernetics, 103(3), 237–253. https://doi.org/10.1007/s00422-010-0401-y.

    Article  MathSciNet  MATH  Google Scholar 

  • Chao, M. Y., Komatsu, H., Fukuto, H. S., Dionne, H. M., & Hart, A. C. (2004). Feeding status and serotonin rapidly and reversibly modulate a Caenorhabditis elegans chemosensory circuit. Proceedings of the National Academy of Science U S A, 101(43), 15512–15517. https://doi.org/10.1073/pnas.0403369101.

    Article  Google Scholar 

  • Cohen, J. D., McClure, S. M., & Angela, J. Y. (2007). Should I stay or should I go? How the human brain manages the trade-off between exploitation and exploration. Philosophical Transactions of the Royal Society B: Biological Sciences, 362(1481), 933–942.

    Article  Google Scholar 

  • Cools, R., Nakamura, K., & Daw, N. D. (2011). Serotonin and dopamine: Unifying affective, activational, and decision functions. Neuropsychopharmacology, 36(1), 98–113. https://doi.org/10.1038/npp.2010.121.

    Article  Google Scholar 

  • Cools, R., Robinson, O. J., & Sahakian, B. (2008). Acute tryptophan depletion in healthy volunteers enhances punishment prediction but does not affect reward prediction. Neuropsychopharmacology, 33(9), 2291–2299. https://doi.org/10.1038/sj.npp.1301598.

    Article  Google Scholar 

  • d’Acremont, M., Lu, Z. L., Li, X., Van der Linden, M., & Bechara, A. (2009). Neural correlates of risk prediction error during reinforcement learning in humans. Neuroimage, 47(4), 1929–1939. https://doi.org/10.1016/j.neuroimage.2009.04.096.

    Article  Google Scholar 

  • Dalley, J. W., Everitt, B. J., & Robbins, T. W. (2011). Impulsivity, compulsivity, and top-down cognitive control. Neuron, 69(4), 680–694.

    Article  Google Scholar 

  • Daw, N. D., Kakade, S., & Dayan, P. (2002). Opponent interactions between serotonin and dopamine. Neural Network, 15(4–6), 603–616.

    Article  Google Scholar 

  • Daw, N. D., O’Doherty, J. P., Dayan, P., Seymour, B., & Dolan, R. J. (2006). Cortical substrates for exploratory decisions in humans. Nature, 441(7095), 876–879. https://doi.org/10.1038/nature04766.

    Article  Google Scholar 

  • Dayan, P., & Huys, Q. (2015). Serotonin’s many meanings elude simple theories. Elife, 4.

    Google Scholar 

  • Dayan, P., & Huys, Q. J. (2008). Serotonin, inhibition, and negative mood. PLoS Computational Biology, 4(2), e4.

    Article  Google Scholar 

  • Dayan, P., & Yu, A. J. (2006). Phasic norepinephrine: A neural interrupt signal for unexpected events. Network: Computation in Neural Systems, 17(4), 335–350.

    Article  Google Scholar 

  • Delaville, C., Zapata, J., Cardoit, L., & Benazzouz, A. (2012). Activation of subthalamic alpha 2 noradrenergic receptors induces motor deficits as a consequence of neuronal burst firing. Neurobiology of Diseases, 47(3), 322–330.

    Article  Google Scholar 

  • DeLong, M. R. (1990). Primate models of movement disorders of basal ganglia origin. Trends in Neurosciences, 13(7), 281–285.

    Article  Google Scholar 

  • Di Giovanni, G., Di Matteo, V., Pierucci, M., & Esposito, E. (2008). Serotonin–dopamine interaction: Electrophysiological evidence. Progress in Brain Research, 172, 45–71.

    Article  Google Scholar 

  • Di Mascio, M., Di Giovanni, G., Di Matteo, V., Prisco, S., & Esposito, E. (1998). Selective serotonin reuptake inhibitors reduce the spontaneous activity of dopaminergic neurons in the ventral tegmental area. Brain Research Bulletin, 46(6), 547–554.

    Article  Google Scholar 

  • Di Matteo, V., Di Giovanni, G., Pierucci, M., & Esposito, E. (2008a). Serotonin control of central dopaminergic function: Focus on in vivo microdialysis studies. Progress in Brain Research, 172, 7–44.

    Article  Google Scholar 

  • Di Matteo, V., Pierucci, M., Esposito, E., Crescimanno, G., Benigno, A., & Di Giovanni, G. (2008b). Serotonin modulation of the basal ganglia circuitry: Therapeutic implication for Parkinson’s disease and other motor disorders. Progress in Brain Research, 172, 423–463.

    Article  Google Scholar 

  • Ding, Y., Won, L., Britt, J. P., Lim, S. A. O., McGehee, D. S., & Kang, U. J. (2011). Enhanced striatal cholinergic neuronal activity mediates l-DOPA–induced dyskinesia in parkinsonian mice. Proceedings of the National Academy of Sciences, 108(2), 840–845.

    Article  Google Scholar 

  • Divac, I., Fonnum, F., & Storm-Mathisen, J. (1977). High affinity uptake of glutamate in terminals of corticostriatal axons. Nature, 266(5600), 377–378.

    Article  Google Scholar 

  • Doya, K. (2002). Metalearning and neuromodulation. Neural Network, 15(4–6), 495–506.

    Article  Google Scholar 

  • Eberle-Wang, K., Mikeladze, Z., Uryu, K., & Chesselet, M. F. (1997). Pattern of expression of the serotonin2C receptor messenger RNA in the basal ganglia of adult rats. Journal of Comparative Neurology, 384(2), 233–247.

    Article  Google Scholar 

  • Economidou, D., Theobald, D. E., Robbins, T. W., Everitt, B. J., & Dalley, J. W. (2012). Norepinephrine and dopamine modulate impulsivity on the five-choice serial reaction time task through opponent actions in the shell and core sub-regions of the nucleus accumbens. Neuropsychopharmacology, 37(9), 2057–2066.

    Article  Google Scholar 

  • Ferre, S., Cortes, R., & Artigas, F. (1994). Dopaminergic regulation of the serotonergic raphe-striatal pathway: Microdialysis studies in freely moving rats. Journal of Neuroscience, 14(8), 4839–4846.

    Google Scholar 

  • Fox, S. H., Chuang, R., & Brotchie, J. M. (2009). Serotonin and Parkinson’s disease: On movement, mood, and madness. Movement Disorders, 24(9), 1255–1266. https://doi.org/10.1002/mds.22473.

    Article  Google Scholar 

  • Frank, M. J. (2005). Dynamic dopamine modulation in the basal ganglia: A neurocomputational account of cognitive deficits in medicated and nonmedicated Parkinsonism. Journal of Cognitive Neuroscience, 17(1), 51–72. https://doi.org/10.1162/0898929052880093.

    Article  Google Scholar 

  • Frank, M. J., Doll, B. B., Oas-Terpstra, J., & Moreno, F. (2009). Prefrontal and striatal dopaminergic genes predict individual differences in exploration and exploitation. Nature Neuroscience, 12(8), 1062–1068.

    Article  Google Scholar 

  • Frank, M. J., Samanta, J., Moustafa, A. A., & Sherman, S. J. (2007a). Hold your horses: Impulsivity, deep brain stimulation, and medication in parkinsonism. Science, 318(5854), 1309–1312.

    Article  Google Scholar 

  • Frank, M. J., Seeberger, L. C., & O’Reilly R, C. (2004). By carrot or by stick: Cognitive reinforcement learning in Parkinsonism. Science, 306(5703), 1940–1943. https://doi.org/10.1126/science.1102941.

  • Gerfen, C. R., Engber, T. M., Mahan, L. C., Susel, Z., Chase, T. N., Monsma, F., et al. (1990). D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science, 250(4986), 1429–1432.

    Article  Google Scholar 

  • Gerfen, C. R., & Wilson, C. J. (1996). Chapter II The basal ganglia. Handbook of Chemical Neuroanatomy, 12, 371–468.

    Google Scholar 

  • Gervais, J., & Rouillard, C. (2000). Dorsal raphe stimulation differentially modulates dopaminergic neurons in the ventral tegmental area and substantia nigra. Synapse, 35(4), 281–291. https://doi.org/10.1002/(sici)1098-2396(20000315)35: 4 < 281::aid-syn6 > 3.0.co;2-a.

  • Gillette, R. (2006). Evolution and function in serotonergic systems. Integrative and Comparative Biology, 46(6), 838–846. https://doi.org/10.1093/icb/icl024.

    Article  Google Scholar 

  • Halford, J. C., Harrold, J. A., Lawton, C. L., & Blundell, J. E. (2005). Serotonin (5-HT) drugs: Effects on appetite expression and use for the treatment of obesity. Current Drug Targets, 6(2), 201–213.

    Article  Google Scholar 

  • Hasbi, A., Fan, T., Alijaniaram, M., Nguyen, T., Perreault, M. L., O’Dowd, B. F., et al. (2009). Calcium signaling cascade links dopamine D1-D2 receptor heteromer to striatal BDNF production and neuronal growth. Proceedings of the National Academy of Science U S A, 106(50), 21377–21382. https://doi.org/10.1073/pnas.0903676106.

    Article  Google Scholar 

  • Hasbi, A., O’Dowd, B. F., & George, S. R. (2010). Heteromerization of dopamine D2 receptors with dopamine D1 or D5 receptors generates intracellular calcium signaling by different mechanisms. Current Opinion in Pharmacology, 10(1), 93–99. https://doi.org/10.1016/j.coph.2009.09.011.

    Article  Google Scholar 

  • Hasbi, A., O’Dowd, B. F., & George, S. R. (2011). Dopamine D1-D2 receptor heteromer signaling pathway in the brain: Emerging physiological relevance. Molecular Brain, 4, 26. https://doi.org/10.1186/1756-6606-4-26.

    Article  Google Scholar 

  • He, Q., Xue, G., Chen, C., Lu, Z., Dong, Q., Lei, X., … Chen, C. (2010). Serotonin transporter gene-linked polymorphic region (5-HTTLPR) influences decision making under ambiguity and risk in a large Chinese sample. Neuropharmacology, 59(6), 518–526.

    Google Scholar 

  • Heiman, M., Schaefer, A., Gong, S., Peterson, J. D., Day, M., Ramsey, K. E., … Surmeier, D. J. (2008). A translational profiling approach for the molecular characterization of CNS cell types. Cell, 135(4), 738–748.

    Google Scholar 

  • Hernandez-Echeagaray, E., Starling, A. J., Cepeda, C., & Levine, M. S. (2004). Modulation of AMPA currents by D2 dopamine receptors in striatal medium-sized spiny neurons: Are dendrites necessary? European Journal of Neuroscience, 19(9), 2455–2463. https://doi.org/10.1111/j.0953-816X.2004.03344.x.

    Article  Google Scholar 

  • Houk, J. C., Bastianen, C., Fansler, D., Fishbach, A., Fraser, D., Reber, P. J., … Simo, L. S. (2007). Action selection and refinement in subcortical loops through basal ganglia and cerebellum. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 362(1485), 1573–1583. https://doi.org/10.1098/rstb.2007.2063.

  • Humphries, M. D., & Prescott, T. J. (2010). The ventral basal ganglia, a selection mechanism at the crossroads of space, strategy, and reward. Progress in Neurobiology, 90(4), 385–417. https://doi.org/10.1016/j.pneurobio.2009.11.003.

    Article  Google Scholar 

  • Jiang, L. H., Ashby, C. R., Jr., Kasser, R. J., & Wang, R. Y. (1990). The effect of intraventricular administration of the 5-HT <sub> 3 </sub> receptor agonist 2-methylserotonin on the release of dopamine in the nucleus accumbens: An in vivo chronocoulometric study. Brain Research, 513(1), 156–160.

    Article  Google Scholar 

  • Jung, A. B., & Bennett, J. P. (1996). Development of striatal dopaminergic function. I. Pre-and postnatal development of mRNAs and binding sites for striatal D1 (D1a) and D2 (D2a) receptors. Developmental Brain Research, 94(2), 109–120.

    Article  Google Scholar 

  • Kahneman, D., & Tversky, A. (1979). Prospect theory: An analysis of decision under risk. Econometrica, 47, 263–292.

    Article  MATH  Google Scholar 

  • Kalva, S. K., Rengaswamy, M., Chakravarthy, V. S., & Gupte, N. (2012). On the neural substrates for exploratory dynamics in basal ganglia: A model. Neural Netw, 32, 65–73. https://doi.org/10.1016/j.neunet.2012.02.031.

    Article  Google Scholar 

  • Kawaguchi, Y., Wilson, C. J., & Emson, P. C. (1990). Projection subtypes of rat neostriatal matrix cells revealed by intracellular injection of biocytin. The Journal of Neuroscience, 10(10), 3421–3438.

    Google Scholar 

  • Kötter, R., & Wickens, J. (1998). Striatal mechanisms in Parkinson’s disease: New insights from computer modeling. Artificial Intelligence in Medicine, 13(1), 37–55.

    Article  Google Scholar 

  • Kravitz, E. A. (2000). Serotonin and aggression: Insights gained from a lobster model system and speculations on the role of amine neurons in a complex behavior. Journal of Comparative Physiology. A, Sensory, Neural, and Behavioral Physiology, 186(3), 221–238.

    Article  Google Scholar 

  • Krishnan, R., Ratnadurai, S., Subramanian, D., Chakravarthy, V. S., & Rengaswamy, M. (2011). Modeling the role of basal ganglia in saccade generation: Is the indirect pathway the explorer? Neural Network, 24(8), 801–813. https://doi.org/10.1016/j.neunet.2011.06.002.

    Article  Google Scholar 

  • Kuhnen, C. M., Samanez-Larkin, G. R., & Knutson, B. (2013). Serotonergic genotypes, neuroticism, and financial choices. PLoS ONE, 8(1), e54632.

    Article  Google Scholar 

  • Lak, A., Stauffer, W. R., & Schultz, W. (2014). Dopamine prediction error responses integrate subjective value from different reward dimensions. Proceedings of the National Academy of Sciences, 111(6), 2343–2348.

    Article  Google Scholar 

  • Le Moine, C., & Bloch, B. (1995). D1 and D2 dopamine receptor gene expression in the rat striatum: Sensitive cRNA probes demonstrate prominent segregation of D1 and D2 mRNAs in distinct neuronal populations of the dorsal and ventral striatum. Journal of Comparative Neurology, 355(3), 418–426.

    Article  Google Scholar 

  • Le Moine, C., Normand, E., & Bloch, B. (1991). Phenotypical characterization of the rat striatal neurons expressing the D1 dopamine receptor gene. Proceedings of the National Academy of Sciences, 88(10), 4205–4209.

    Article  Google Scholar 

  • Lee, S. P., So, C. H., Rashid, A. J., Varghese, G., Cheng, R., Lanca, A. J., . . . George, S. R. (2004). Dopamine D1 and D2 receptor Co-activation generates a novel phospholipase C-mediated calcium signal. Journal of Biological Chemistry, 279(34), 35671–35678. https://doi.org/10.1074/jbc.m401923200.

  • Lobo, M. K., Karsten, S. L., Gray, M., Geschwind, D. H., & Yang, X. W. (2006). FACS-array profiling of striatal projection neuron subtypes in juvenile and adult mouse brains. Nature Neuroscience, 9(3), 443–452.

    Article  Google Scholar 

  • Long, A. B., Kuhn, C. M., & Platt, M. L. (2009). Serotonin shapes risky decision making in monkeys. Social Cognitive Affective Neuroscience, 4(4), 346–356. https://doi.org/10.1093/scan/nsp020.

    Article  Google Scholar 

  • Lopez-Ibor, J. (1992). Serotonin and psychiatric disorders. International Clinical Psychopharmacology.

    Google Scholar 

  • Markowitz, H. (1952). Portfolio selection. The Journal of Finance, 7(1), 77–91. https://doi.org/10.2307/2975974.

    Google Scholar 

  • Matamales, M., Bertran-Gonzalez, J., Salomon, L., Degos, B., Deniau, J.-M., Valjent, E., . . . Girault, J.-A. (2009). Striatal medium-sized spiny neurons: identification by nuclear staining and study of neuronal subpopulations in BAC transgenic mice. PLoS One, 4(3), e4770.

    Google Scholar 

  • Matsuda, W., Furuta, T., Nakamura, K. C., Hioki, H., Fujiyama, F., Arai, R., et al. (2009). Single nigrostriatal dopaminergic neurons form widely spread and highly dense axonal arborizations in the neostriatum. The Journal of Neuroscience, 29(2), 444–453.

    Article  Google Scholar 

  • McGeorge, A. J., & Faull, R. L. (1989). The organization of the projection from the cerebral cortex to the striatum in the rat. Neuroscience, 29(3), 503–537.

    Article  Google Scholar 

  • Mink, J. W. (1996). The basal ganglia: Focused selection and inhibition of competing motor programs. Progress in Neurobiology, 50(4), 381.

    Article  Google Scholar 

  • Morita, K., Morishima, M., Sakai, K., & Kawaguchi, Y. (2012). Reinforcement learning: Computing the temporal difference of values via distinct corticostriatal pathways. Trends in Neurosciences, 35(8), 457–467.

    Article  Google Scholar 

  • Moyer, J. T., Wolf, J. A., & Finkel, L. H. (2007). Effects of dopaminergic modulation on the integrative properties of the ventral striatal medium spiny neuron. Journal of Neurophysiology, 98(6), 3731–3748. https://doi.org/10.1152/jn.00335.2007.

    Article  Google Scholar 

  • Murphy, S. E., Longhitano, C., Ayres, R. E., Cowen, P. J., Harmer, C. J., & Rogers, R. D. (2009). The role of serotonin in nonnormative risky choice: The effects of tryptophan supplements on the “reflection effect” in healthy adult volunteers. Journal of Cognitive Neuroscience, 21(9), 1709–1719. https://doi.org/10.1162/jocn.2009.21122.

    Article  Google Scholar 

  • Nadjar, A., Brotchie, J. M., Guigoni, C., Li, Q., Zhou, S.-B., Wang, G.-J., … Bezard, E. (2006). Phenotype of striatofugal medium spiny neurons in parkinsonian and dyskinetic nonhuman primates: a call for a reappraisal of the functional organization of the basal ganglia. The Journal of Neuroscience, 26(34), 8653–8661.

    Google Scholar 

  • Nakamura, K. (2013). The role of the dorsal raphé nucleus in reward-seeking behavior. Frontiers in Integrative Neuroscience, 7.

    Google Scholar 

  • Parent, A., & Hazrati, L.-N. (1995). Functional anatomy of the basal ganglia. II. The place of subthalamic nucleus and external pallidium in basal ganglia circuitry. Brain Research Reviews, 20(1), 128–154.

    Article  Google Scholar 

  • Perreault, M. L., Fan, T., Alijaniaram, M., O’Dowd, B. F., & George, S. R. (2012). Dopamine D1-D2 receptor heteromer in dual phenotype GABA/glutamate-coexpressing striatal medium spiny neurons: Regulation of BDNF, GAD67 and VGLUT1/2. PLoS ONE, 7(3), e33348. https://doi.org/10.1371/journal.pone.0033348.

    Article  Google Scholar 

  • Perreault, M. L., Hasbi, A., Alijaniaram, M., Fan, T., Varghese, G., Fletcher, P. J., . . . George, S. R. (2010). The dopamine D1-D2 receptor heteromer localizes in dynorphin/enkephalin neurons: increased high affinity state following amphetamine and in schizophrenia. Journal of Biological Chemistry, 285(47), 36625–36634. https://doi.org/10.1074/jbc.m110.159954.

  • Perreault, M. L., Hasbi, A., O’Dowd, B. F., & George, S. R. (2011). The dopamine d1-d2 receptor heteromer in striatal medium spiny neurons: Evidence for a third distinct neuronal pathway in Basal Ganglia. Frontiers in Neuroanatomy, 5, 31. https://doi.org/10.3389/fnana.2011.00031.

    Article  Google Scholar 

  • Preuschoff, K., Bossaerts, P., & Quartz, S. R. (2006). Neural differentiation of expected reward and risk in human subcortical structures. Neuron, 51(3), 381–390. https://doi.org/10.1016/j.neuron.2006.06.024.

    Article  Google Scholar 

  • Rashid, A. J., O’Dowd, B. F., Verma, V., & George, S. R. (2007). Neuronal Gq/11-coupled dopamine receptors: An uncharted role for dopamine. Trends in Pharmacological Sciences, 28(11), 551–555.

    Article  Google Scholar 

  • Reynolds, J. N., Hyland, B. I., & Wickens, J. R. (2001). A cellular mechanism of reward-related learning. Nature, 413(6851), 67–70.

    Article  Google Scholar 

  • Reynolds, J. N., & Wickens, J. R. (2002). Dopamine-dependent plasticity of corticostriatal synapses. Neural Network, 15(4–6), 507–521.

    Article  Google Scholar 

  • Robinson, O. J., Cools, R., & Sahakian, B. J. (2012). Tryptophan depletion disinhibits punishment but not reward prediction: Implications for resilience. Psychopharmacology (Berl), 219(2), 599–605. https://doi.org/10.1007/s00213-011-2410-5.

    Article  Google Scholar 

  • Rogers, R. D. (2011). The roles of dopamine and serotonin in decision making: Evidence from pharmacological experiments in humans. Neuropsychopharmacology, 36(1), 114–132. https://doi.org/10.1038/npp.2010.165.

    Article  Google Scholar 

  • Schultz, W. (1998). Predictive reward signal of dopamine neurons. Journal of Neurophysiology, 80(1), 1–27.

    Article  MathSciNet  Google Scholar 

  • Schultz, W. (2013). Updating dopamine reward signals. Current Opinion in Neurobiology, 23(2), 229–238.

    Article  Google Scholar 

  • Seymour, B., Daw, N. D., Roiser, J. P., Dayan, P., & Dolan, R. (2012). Serotonin selectively modulates reward value in human decision-making. Journal of Neuroscience, 32(17), 5833–5842. https://doi.org/10.1523/JNEUROSCI.0053-12.2012.

    Article  Google Scholar 

  • Shuen, J. A., Chen, M., Gloss, B., & Calakos, N. (2008). Drd1a-tdTomato BAC transgenic mice for simultaneous visualization of medium spiny neurons in the direct and indirect pathways of the basal ganglia. The Journal of Neuroscience, 28(11), 2681–2685.

    Article  Google Scholar 

  • So, C. H., Verma, V., Alijaniaram, M., Cheng, R., Rashid, A. J., O’Dowd, B. F., et al. (2009). Calcium signaling by dopamine D5 receptor and D5-D2 receptor hetero-oligomers occurs by a mechanism distinct from that for dopamine D1-D2 receptor hetero-oligomers. Molecular Pharmacology, 75(4), 843–854. https://doi.org/10.1124/mol.108.051805.

    Article  Google Scholar 

  • Spehlmann, R., & Stahl, S. (1976). Dopamine acetylcholine imbalance in Parkinson’s disease: Possible regenerative overgrowth of cholinergic axon terminals. The Lancet, 307(7962), 724–726.

    Article  Google Scholar 

  • Stauffer, W. R., Lak, A., & Schultz, W. (2014). Dopamine reward prediction error responses reflect marginal utility. Current Biology, 24(21), 2491–2500.

    Article  Google Scholar 

  • Stopper, C. M., & Floresco, S. B. (2011). Contributions of the nucleus accumbens and its subregions to different aspects of risk-based decision making. Cognitive Affective Behavioral Neuroscience, 11(1), 97–112. https://doi.org/10.3758/s13415-010-0015-9.

    Article  Google Scholar 

  • Stringer, S., Rolls, E., Trappenberg, T., & De Araujo, I. (2002). Self-organizing continuous attractor networks and path integration: Two-dimensional models of place cells. Network: Computation in Neural Systems, 13(4), 429–446.

    Article  MATH  Google Scholar 

  • Surmeier, D., & Kitai, S. (1993). D 1 and D 2 dopamine receptor modulation of sodium and potassium currents in rat neostriatal neurons. Progress in Brain Research, 99, 309–324.

    Article  Google Scholar 

  • Surmeier, D. J., Ding, J., Day, M., Wang, Z., & Shen, W. (2007). D1 and D2 dopamine-receptor modulation of striatal glutamatergic signaling in striatal medium spiny neurons. Trends in Neurosciences, 30(5), 228–235. https://doi.org/10.1016/j.tins.2007.03.008.

    Article  Google Scholar 

  • Sutton, R. S., & Barto, A. G. (1998). Reinforcement learning: An introduction. Adaptive computations and machine learning. Bradford: MIT Press.

    Google Scholar 

  • Suzuki, M., Hurd, Y. L., Sokoloff, P., Schwartz, J. C., & Sedvall, G. (1998). D3 dopamine receptor mRNA is widely expressed in the human brain. Brain Research, 779(1–2), 58–74.

    Article  Google Scholar 

  • Swann, A. C., Lijffijt, M., Lane, S. D., Cox, B., Steinberg, J. L., & Moeller, F. G. (2013). Norepinephrine and impulsivity: Effects of acute yohimbine. Psychopharmacology (Berl), 229(1), 83–94.

    Article  Google Scholar 

  • Tai, L.-H., Lee, A. M., Benavidez, N., Bonci, A., & Wilbrecht, L. (2012). Transient stimulation of distinct subpopulations of striatal neurons mimics changes in action value. Nature Neuroscience, 15(9), 1281–1289.

    Article  Google Scholar 

  • Tanaka, S. C., Schweighofer, N., Asahi, S., Shishida, K., Okamoto, Y., Yamawaki, S., et al. (2007). Serotonin differentially regulates short- and long-term prediction of rewards in the ventral and dorsal striatum. PLoS ONE, 2(12), e1333. https://doi.org/10.1371/journal.pone.0001333.

    Article  Google Scholar 

  • Tanaka, S. C., Shishida, K., Schweighofer, N., Okamoto, Y., Yamawaki, S., & Doya, K. (2009). Serotonin affects association of aversive outcomes to past actions. Journal of Neuroscience, 29(50), 15669–15674. https://doi.org/10.1523/JNEUROSCI.2799-09.2009.

    Article  Google Scholar 

  • Tops, M., Russo, S., Boksem, M. A., & Tucker, D. M. (2009). Serotonin: Modulator of a drive to withdraw. Brain and Cognition, 71(3), 427–436. https://doi.org/10.1016/j.bandc.2009.03.009.

    Article  Google Scholar 

  • Valjent, E., Bertran-Gonzalez, J., Hervé, D., Fisone, G., & Girault, J.-A. (2009). Looking BAC at striatal signaling: Cell-specific analysis in new transgenic mice. Trends in Neurosciences, 32(10), 538–547.

    Article  Google Scholar 

  • Wang, R., Macmillan, L., Fremeau, R., Jr., Magnuson, M., Lindner, J., & Limbird, L. (1996). Expression of α2-adrenergic receptor subtypes in the mouse brain: Evaluation of spatial and temporal information imparted by 3 kb of 5′ regulatory sequence for the α2A AR-receptor gene in transgenic animals. Neuroscience, 74(1), 199–218.

    Article  Google Scholar 

  • Ward, R. P., & Dorsa, D. M. (1996). Colocalization of serotonin receptor subtypes 5-HT2A, 5-HT2C, and 5-HT6 with neuropeptides in rat striatum. Journal of Comparative Neurology, 370(3), 405–414.

    Article  Google Scholar 

  • Zhong, S., Israel, S., Xue, H., Ebstein, R. P., & Chew, S. H. (2009a). Monoamine oxidase A gene (MAOA) associated with attitude towards longshot risks. PLoS ONE, 4(12), e8516.

    Article  Google Scholar 

  • Zhong, S., Israel, S., Xue, H., Sham, P. C., Ebstein, R. P., & Chew, S. H. (2009b). A neurochemical approach to valuation sensitivity over gains and losses. Proceedings of the Royal Society B: Biological Sciences, 276(1676), 4181–4188.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to V. Srinivasa Chakravarthy .

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Balasubramani, P.P., Srinivasa Chakravarthy, V., Ravindran, B., Moustafa, A.A. (2018). Modeling Serotonin’s Contributions to Basal Ganglia Dynamics. In: Computational Neuroscience Models of the Basal Ganglia. Cognitive Science and Technology. Springer, Singapore. https://doi.org/10.1007/978-981-10-8494-2_12

Download citation

  • DOI: https://doi.org/10.1007/978-981-10-8494-2_12

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-10-8493-5

  • Online ISBN: 978-981-10-8494-2

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics