Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter April 9, 2014

Serotonin regulation of subthalamic neurons

Shengyuan Ding and Fu-Ming Zhou


The subthalamic nucleus (STN) is a key component of the basal ganglia. As the only basal ganglia nucleus comprised of mostly glutamatergic neurons, STN neurons provide a key driving force to their target neurons. Thus, regulation of STN neuron activity is important. One STN regulator is the serotonin (5-HT) system. The STN receives a dense 5-HT innervation. 5-HT1A, 5-HT1B, 5-HT2C, and 5-HT4 receptors are expressed in the STN. 5-HT may regulate the STN via several mechanisms. First, 5-HT may affect STN neuron excitability directly by either inhibiting a subpopulation of STN neurons via activation of 5-HT1A receptors or exciting STN neurons through activation of 5-HT2C and 5-HT4 receptors. Second, 5-HT may affect synaptic inputs to the STN. Via activation of 5-HT1B receptors on the afferent terminals, 5-HT inhibits glutamatergic input to the STN, but the inhibitory effect on GABAergic input is smaller. Third, 5-HT may regulate the STN glutamatergic output by activating presynaptic 5-HT1B receptors, thus reducing burst firing in target neurons. Last, 5-HT may affect glutamate release at the intra-STN axon collaterals and regulate the recurrent excitation. These mechanisms may work in concert to fine-tune the intensity and pattern of STN activity and reduce STN output bursts.

Corresponding author: Fu-Ming Zhou, Department of Pharmacology, University of Tennessee College of Medicine, Memphis, TN 38163, USA, e-mail:


This work was supported by NIH grants R01NS058850 and R03NS076960.


Afsharpour, S. (1985). Topographical projections of the cerebral cortex to the subthalamic nucleus. J. Comp. Neurol. 236, 14–28.10.1002/cne.902360103Search in Google Scholar

Ammari, R., Lopez, C., Bioulac, B., Garcia, L., and Hammond, C. (2010). Subthalamic nucleus evokes similar long lasting glutamatergic excitations in pallidal, entopeduncular and nigral neurons in the basal ganglia slice. Neuroscience 166, 808–818.10.1016/j.neuroscience.2010.01.011Search in Google Scholar

Aristieta, A., Morera-Herreras, T., Ruiz-Ortega, J.A., Miguelez, C., Vidaurrazaga, I., Arrue, A., Zumarraga, M., and Ugedo, L. (2013). Modulation of the subthalamic nucleus activity by serotonergic agents and fluoxetine administration. Psychopharmacology (Berl.) 2013 Nov 24. Epub ahead of print.Search in Google Scholar

Atherton, J.F. and Bevan, M.D. (2005). Ionic mechanisms underlying autonomous action potential generation in the somata and dendrites of GABAergic substantia nigra pars reticulata neurons in vitro. J. Neurosci. 25, 8272–8281.10.1523/JNEUROSCI.1475-05.2005Search in Google Scholar

Azmitia, E.C. and Nixon, R. (2008). Dystrophic serotonergic axons in Neurodegenerative diseases. Brain Res. 1217, 185–194.10.1016/j.brainres.2008.03.060Search in Google Scholar

Barnes, N.M. and Sharp, T. (1999). A review of central 5-HT receptors and their function. Neuropharmacology 38, 1083–1152.10.1016/S0028-3908(99)00010-6Search in Google Scholar

Barwick, V.S., Jones, D.H., Richter, J.T., Hicks, P.B., and Young, K.A. (2000). Subthalamic nucleus microinjections of 5-HT2 receptor antagonists suppress stereotypy in rats. Neuroreport 11, 267–270.10.1097/00001756-200002070-00009Search in Google Scholar PubMed

Baumgarten, H.G. and Grozdanovic, Z. (1997) Anatomy of the central serotoninergic projection systems. Serotoninergic neurons and 5-HT receptors in the CNS. H.G. Baumgarten and M. Gothert, eds. (Berlin: Springer-Verlag), pp. 41–89.Search in Google Scholar

Baunez, C., Yelnik, J., and Mallet, L. (2011). Six questions on the subthalamic nucleus: lessons from animal models and from stimulated patients. Neuroscience 198, 193–204.10.1016/j.neuroscience.2011.09.059Search in Google Scholar PubMed

Belforte, J.E. and Pazo, J.H. (2004). Turning behaviour induced by stimulation of the 5-HT receptors in the subthalamic nucleus. Eur. J. Neurosci. 19, 346–355.10.1111/j.0953-816X.2003.03125.xSearch in Google Scholar PubMed

Ben-Daniel, R., Deuther-Conrad, W., Scheunemann, M., Steinbach, J., Brust, P., and Mishani, E. (2008). Carbon-11 labeled indolylpropylamine analog as a new potential PET agent for imaging of the serotonin transporter. Bioorg. Med. Chem. 16, 6364–6370.10.1016/j.bmc.2008.05.006Search in Google Scholar PubMed

Benedetti, F., Lanotte, M., Colloca, L., Ducati, A., Zibetti, M., and Lopiano, L. (2009). Electrophysiological properties of thalamic, subthalamic and nigral neurons during the anti-parkinsonian placebo response. J. Physiol. 587, 3869–3883.10.1113/jphysiol.2009.169425Search in Google Scholar PubMed PubMed Central

Bergman, H., Wichmann, T., Karmon, B., and DeLong, M.R. (1994). The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism. J Neurophysiol. 72, 507–520.10.1152/jn.1994.72.2.507Search in Google Scholar

Beurrier, C., Bioulac, B., and Hammond, C. (2000). Slowly inactivating sodium current (I(NaP)) underlies single-spike activity in rat subthalamic neurons. J. Neurophysiol. 83, 1951–197.10.1152/jn.2000.83.4.1951Search in Google Scholar

Bevan, M.D. and Wilson, C.J. (1999) Mechanisms underlying spontaneous oscillation and rhythmic firing in rat subthalamic neurons. J. Neurosci. 19, 76177628.10.1523/JNEUROSCI.19-17-07617.1999Search in Google Scholar

Bevan, M.D., Magill, P.J., Hallworth, N.E., Bolam, J.P., and Wilson, C.J. (2002a). Regulation of the timing and pattern of action potential generation in rat subthalamic neurons in vitro by GABA-A IPSPs. J. Neurophysiol. 87, 1348–1362.10.1152/jn.00582.2001Search in Google Scholar

Bevan, M.D., Magill, P.J., Terman, D., Bolam, J.P., and Wilson, C.J. (2002b). Move to the rhythm: oscillations in the subthalamic nucleus-external globus pallidus network. Trends Neurosci. 25, 525–531.10.1016/S0166-2236(02)02235-XSearch in Google Scholar

Bevan, M.D., Hallworth, N.E., and Baufreton, J. (2007). GABAergic control of the subthalamic nucleus. Prog. Brain. Res. 160, 173–188.10.1016/S0079-6123(06)60010-1Search in Google Scholar

Boschert, U., Amara, D.A., Segu, L., and Hen, R. (1994). The mouse 5-hydroxytryptamine1B receptor is localized predominantly on axon terminals. Neuroscience 58, 167–182.10.1016/0306-4522(94)90164-3Search in Google Scholar

Bockaert, J., Claeysen, S., Bécamel, C., Dumuis, A., and Marin, P. (2006). Neuronal 5-HT metabotropic receptors: fine-tuning of their structure, signaling, and roles in synaptic modulation. Cell Tissue Res. 326, 553–572.10.1007/s00441-006-0286-1Search in Google Scholar PubMed

Braak, H., Ghebremedhin, E., Rüb, U., Bratzke, H., and Del Tredici, K. (2004). Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res. 318, 121–134.10.1007/s00441-004-0956-9Search in Google Scholar PubMed

Bruinvels, A.T., Palacios, J.M., and Hoyer, D. (1993). Autoradiographic characterisation and localisation of 5-HT1D compared to 5-HT1B binding sites in rat brain. Naunyn Schmiedebergs Arch. Pharmacol. 347, 569–582.Search in Google Scholar

Charpier, S., Burrier, C., and Paz, J.T. (2010). The subthalamic nucleus: from in vitro to in vivo mechanisms. Handbook of Basal Ganglia Structure and Function. H. Steiner and K.Y. Tseng, eds. (Waltham, MA: Academic Press), pp. 259–273.10.1016/B978-0-12-374767-9.00015-9Search in Google Scholar

Clemett, D.A., Punhani, T., Duxon, M.S., Blackburn, T.P., and Fone, K.C. (2000). Immunohistochemical localisation of the 5-HT2C receptor protein in the rat CNS. Neuropharmacology 39, 123–132.10.1016/S0028-3908(99)00086-6Search in Google Scholar

Compan, V., Daszuta, A., Salin, P., Sebben, M., Bockaert, J., and Dumuis, A. (1996). Lesion study of the distribution of serotonin 5-HT4 receptors in rat basal ganglia and hippocampus. Eur. J. Neurosci. 8, 2591–2598.10.1111/j.1460-9568.1996.tb01553.xSearch in Google Scholar

Creed, M.C., Hamani, C., Bridgman, A., Fletcher, P.J., and Nobrega, J.N. (2010). Contribution of decreased serotonin release to the antidyskinetic effects of deep brain stimulation in a rodent model of tardive dyskinesia: comparison of the subthalamic and entopeduncular nuclei. J. Neurosci. 32, 9574–9581.10.1523/JNEUROSCI.1196-12.2012Search in Google Scholar

Degos, B., Deniau, J.M., Le Cam, J., Mailly, P., and Maurice, N. (2008). Evidence for a direct subthalamo-cortical loop circuit in the rat. Eur. J. Neurosci. 27, 2599–2610.10.1111/j.1460-9568.2008.06229.xSearch in Google Scholar

Delaville, C., Chetrit, J., Abdallah, K., Morin, S., Cardoit, L., De Deurwaerdère, P., and Benazzouz, A. (2012a). Emerging dysfunctions consequent to combined monoaminergic depletions in Parkinsonism. Neurobiol. Dis. 45, 763–773.10.1016/j.nbd.2011.10.023Search in Google Scholar

Delaville, C., Navailles, S., and Benazzouz, A. (2012b). Effects of noradrenaline and serotonin depletions on the neuronal activity of globus pallidus and substantia nigra pars reticulata in experimental parkinsonism. Neuroscience 202, 424–433.10.1016/j.neuroscience.2011.11.024Search in Google Scholar

Ding, S., Li, L., and Zhou, F.M. (2013). Presynaptic serotonergic gating of the subthalamonigral glutamatergic projection. J. Neurosci. 33, 4875–4885.10.1523/JNEUROSCI.4111-12.2013Search in Google Scholar

Ding, S., Matta, S.G., and Zhou, F.M. (2011a). Kv3-like potassium channels are required for sustained high-frequency firing in basal ganglia output neurons. J. Neurophysiol. 105, 554–570.10.1152/jn.00707.2010Search in Google Scholar

Ding, S., Wei, W., and Zhou, F.M. (2011b). Molecular and functional differences in voltage-activated sodium currents between GABA projection neurons and dopamine neurons in the substantia nigra. J. Neurophysiol. 106, 3019–3034.10.1152/jn.00305.2011Search in Google Scholar

Eberle-Wang, K., Lucki, I., and Chesselet, M.F. (1996). A role for the subthalamic nucleus in 5-HT2C-induced oral dyskinesia. Neuroscience 72, 117–28.10.1016/0306-4522(95)00548-XSearch in Google Scholar

Eberle-Wang, K., Mikeladze, Z., Uryu, K., and Chesselet, M.F. (1997). Pattern of expression of the serotonin2C receptor messenger RNA in the basal ganglia of adult rats. J Comp Neurol. 384, 233–247.10.1002/(SICI)1096-9861(19970728)384:2<233::AID-CNE5>3.0.CO;2-2Search in Google Scholar

Flores, G., Rosales, M.G., Hernández, S., Sierra, A., and Aceves, J. (1995). 5-Hydroxytryptamine increases spontaneous activity of subthalamic neurons in the rat. Neurosci. Lett. 192, 17–20.10.1016/0304-3940(95)11597-PSearch in Google Scholar

Follett, K.A., Weaver, F.M., Stern, M., Hur, K., Harris, C.L., Luo, P., Marks, W.J. Jr, Rothlind, J., Sagher, O., Moy, C., et al. CSP 468 Study Group. (2010). Pallidal versus subthalamic deep-brain stimulation for Parkinson’s disease. N. Engl. J. Med. 362, 2077–2091.10.1056/NEJMoa0907083Search in Google Scholar

Fujimoto, K. and Kita, H. (1993). Response characteristics of subthalamic neurons to the stimulation of the sensorimotor cortex in the rat. Brain Res. 609, 185–192.10.1016/0006-8993(93)90872-KSearch in Google Scholar

Gerfen, C.R. and Bolam, J.P. (2010). The neuroanatomical organization of the basal ganglia. Handbook of basal ganglia structure and function. H. Steiner and K.Y. Tseng, eds. (Waltham, MA: Academic Press), pp. 3–28.10.1016/B978-0-12-374767-9.00001-9Search in Google Scholar

Hallworth, N.E. and Bevan, M.D. (2005). Globus pallidus neurons dynamically regulate the activity pattern of subthalamic nucleus neurons through the frequency-dependent activation of postsynaptic GABAA and GABAB receptors. J. Neurosci. 25, 6304–6315.10.1523/JNEUROSCI.0450-05.2005Search in Google Scholar

Hallworth, N.E., Wilson, C.J., and Bevan, M.D. (2003). Apamin-sensitive small conductance calcium-activated potassium channels, through their selective coupling to voltage-gated calcium channels, are critical determinants of the precision, pace, and pattern of action potential generation in rat subthalamic nucleus neurons in vitro. J. Neurosci. 23, 7525–7542.10.1523/JNEUROSCI.23-20-07525.2003Search in Google Scholar

Hammond, C. and Yelnik, J. (1983). Intracellular labelling of rat subthalamic neurones with horseradish peroxidase: computer analysis of dendrites and characterization of axon arborization. Neuroscience 8, 781–790.10.1016/0306-4522(83)90009-XSearch in Google Scholar

Hannon, J. and Hoyer, D. (2008). Molecular biology of 5-HT receptors. Behav. Brain Res. 195, 198–213.10.1016/j.bbr.2008.03.020Search in Google Scholar

Hashemi, P., Dankoski, E.C., Wood, K.M., Ambrose, R.E., and Wightman, R.M. (2011). In vivo electrochemical evidence for simultaneous 5-HT and histamine release in the rat substantia nigra pars reticulata following medial forebrain bundle stimulation. J. Neurochem. 118, 749–759.10.1111/j.1471-4159.2011.07352.xSearch in Google Scholar

Hashemi, P., Dankoski, E.C., Lama, R., Wood, K.M., Takmakov, P., and Wightman, R.M. (2012) Brain dopamine and serotonin differ in regulation and its consequences. Proc. Natl. Acad. Sci. USA. 109, 11510–11515.10.1073/pnas.1201547109Search in Google Scholar

Haynes, W.I. and Haber, S.N. (2013). The organization of prefrontal-subthalamic inputs in primates provides an anatomical substrate for both functional specificity and integration: implications for Basal Ganglia models and deep brain stimulation. J. Neurosci. 33, 4804–4814.10.1523/JNEUROSCI.4674-12.2013Search in Google Scholar

Hikosaka, O., Takikawa, Y., and Kawagoe, R. (2000). Role of the basal ganglia in the control of purposive saccadic eye movements. Physiol. Rev. 80, 953–978.10.1152/physrev.2000.80.3.953Search in Google Scholar

Honda, T. and Semba, K. (1995). An ultrastructural study of cholinergic and non-cholinergic neurons in the laterodorsal and pedunculopontine tegmental nuclei in the rat. Neuroscience 68, 837–853.10.1016/0306-4522(95)00177-KSearch in Google Scholar

Huot, P., Fox, S.H., and Brotchie, J.M. (2011). The serotonergic system in Parkinson’s disease. Prog. Neurobiol. 95, 163–212.10.1016/j.pneurobio.2011.08.004Search in Google Scholar PubMed

Isoda, M. and Hikosaka, O. (2008). Role for subthalamic nucleus neurons in switching from automatic to controlled eye movement. J. Neurosci. 28, 7209–7218.10.1523/JNEUROSCI.0487-08.2008Search in Google Scholar PubMed PubMed Central

Jacobs, B.L. and Azmitia, E.C. (1992). Structure and function of the brain serotonin system. Physiol. Rev. 72, 165–229.10.1152/physrev.1992.72.1.165Search in Google Scholar PubMed

Jaunarajs, K.L., Dupre, K.B., Steiniger, A., Klioueva, A., Moore, A., Kelly, C., and Bishop, C. (2009). Serotonin 1B receptor stimulation reduces D1 receptor agonist-induced dyskinesia. Neuroreport 20, 1265–1269.10.1097/WNR.0b013e3283300fd7Search in Google Scholar PubMed

Kish, S.J., Tong, J., Hornykiewicz, O., Rajput, A., Chang, L.J, Guttman, M., and Furukawa, Y. (2008). Preferential loss of serotonin markers in caudate versus putamen in Parkinson’s disease. Brain 131, 120–131.Search in Google Scholar

Kita, H. and Kitai, S.T. (1987). Efferent projections of the subthalamic nucleus in the rat: light and electron microscopic analysis with the PHA-L method. J. Comp. Neurol. 260, 435–452.10.1002/cne.902600309Search in Google Scholar PubMed

Kita, H. and Kita, T. (2011) Cortical stimulation evokes abnormal responses in the dopamine-depleted rat basal ganglia. J. Neurosci. 31, 10311–10322.10.1523/JNEUROSCI.0915-11.2011Search in Google Scholar PubMed PubMed Central

Kita, T. and Kita, H. (2012). The subthalamic nucleus is one of multiple innervation sites for long-range corticofugal axons: a single-axon tracing study in the rat. J. Neurosci. 32, 5990–5999.10.1523/JNEUROSCI.5717-11.2012Search in Google Scholar PubMed PubMed Central

Kita, H., Chang, H.T., and Kitai, S.T. (1983). The morphology of intracellularly labeled rat subthalamic neurons: a light microscopic analysis. J. Comp. Neurol. 215, 245–257.10.1002/cne.902150302Search in Google Scholar PubMed

Kitai, S.T. and Kita, H. (1987). Anatomy and physiology of the subthalamic nucleus: a driving force of the basal ganglia. The basal ganglia, Vol. II. M.B. Carpenter and A. Jayaraman, eds. (New York: Plenum), pp. 357–373.10.1007/978-1-4684-5347-8_25Search in Google Scholar

Koshimizu, Y., Fujiyama, F., Nakamura, K.C., Furuta, T., and Kaneko, T. (2013). Quantitative analysis of axon bouton distribution of subthalamic nucleus neurons in the rat by single neuron visualization with a viral vector. J. Comp. Neurol. 521, 2125–2146.10.1002/cne.23277Search in Google Scholar PubMed

Kravitz, A.V., Freeze, B.S., Parker, P.R., Kay, K., Thwin, M.T., Deisseroth, K., and Kreitzer, A.C. (2010). Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry. Nature 466, 622–626.10.1038/nature09159Search in Google Scholar PubMed PubMed Central

Kreiss, D.S., Mastropietro, C.W., Rawji, S.S., and Walters, J.R. (1997). The response of subthalamic nucleus neurons to dopamine receptor stimulation in a rodent model of Parkinson’s disease. J. Neurosci. 17, 6807–6819.10.1523/JNEUROSCI.17-17-06807.1997Search in Google Scholar

Lévesque, J.C. and Parent, A. (2005). GABAergic interneurons in human subthalamic nucleus. Mov. Disord. 20, 574–584.10.1002/mds.20374Search in Google Scholar PubMed

Li, Y.W. and Bayliss, D.A. (1998). Presynaptic inhibition by 5-HT1B receptors of glutamatergic synaptic inputs onto serotonergic caudal raphe neurones in rat. J. Physiol. 510, 121–134.10.1111/j.1469-7793.1998.121bz.xSearch in Google Scholar PubMed PubMed Central

Liu, J., Chu, Y.X., Zhang, Q.J., Wang, S., Feng, J., and Li, Q. (2007). 5,7-dihydroxytryptamine lesion of the dorsal raphe nucleus alters neuronal activity of the subthalamic nucleus in normal and 6-hydroxydopamine-lesioned rats. Brain Res. 1149, 216–222.10.1016/j.brainres.2007.02.052Search in Google Scholar PubMed

Magill, P.J., Sharott, A., Bevan, M.D., Brown, P., and Bolam, J.P. (2004). Synchronous unit activity and local field potentials evoked in the subthalamic nucleus by cortical stimulation. J. Neurophysiol. 92, 700–714.10.1152/jn.00134.2004Search in Google Scholar PubMed

Maroteaux, L., Saudou, F., Amlaiky, N., Boschert, U., Plassat, J.L., and Hen, R. (1992). Mouse 5HT1B serotonin receptor: cloning, functional expression, and localization in motor control centers. Proc. Natl. Acad. Sci. USA. 89, 3020–3024.10.1073/pnas.89.7.3020Search in Google Scholar

Martinez-Price, D.L., and Geyer, M.A. (2002). Subthalamic 5-HT(1A) and 5-HT(1B) receptor modulation of RU 24969-induced behavioral profile in rats. Pharmacol. Biochem. Behav. 71, 569–580.10.1016/S0091-3057(01)00704-3Search in Google Scholar

Maurice, N., Deniau, J.M., Glowinski, J., and Thierry, A.M. (1998). Relationships between the prefrontal cortex and the basal ganglia in the rat: physiology of the corticosubthalamic circuits. J. Neurosci. 18, 9539–9546.10.1523/JNEUROSCI.18-22-09539.1998Search in Google Scholar

Millan, M.J., Marin, P., Bockaert, J., and Mannoury la Cour, C. (2008). Signaling at G-protein-coupled serotonin receptors: recent advances and future research directions. Trends Pharmacol. Sci. 29, 454–464.10.1016/ in Google Scholar

Mizutani, H., Hori, T., and Takahashi, T. (2006). 5-HT1B receptor-mediated presynaptic inhibition at the calyx of Held of immature rats. Eur. J. Neurosci. 24, 1946–1954.10.1111/j.1460-9568.2006.05063.xSearch in Google Scholar

Moukhles, H., Bosler, O., Bolam, J.P., Vallee, A., Umbriaco, D., Geffard, M., and Doucet, G. (1997). Quantitative and morphometric data indicate precise cellular interactions between serotonin terminals and postsynaptic targets in rat substantia nigra. Neuroscience 76, 1159–1171.10.1016/S0306-4522(96)00452-6Search in Google Scholar

Mrakic-Sposta, S., Marceglia, S., Egidi, M., Carrabba, G., Rampini, P., Locatelli, M., Foffani, G., Accolla, E., Cogiamanian, F., Tamma, F., et al. (2008). Extracellular spike microrecordings from the subthalamic area in Parkinson’s disease. J. Clin. Neurosci. 15, 559–567.10.1016/j.jocn.2007.02.091Search in Google Scholar

Nakanishi, H., Kita, H., and Kitai, S.T. (1987). Electrical membrane properties of rat subthalamic neurons in an in vitro slice preparation. Brain Res. 437, 35–44.10.1016/0006-8993(87)91524-1Search in Google Scholar

Nambu, A., Tokuno, H., and Takada, M. (2002). Functional significance of the cortico-subthalamo-pallidal “hyperdirect” pathway. Neurosci. Res. 43, 111–117.10.1016/S0168-0102(02)00027-5Search in Google Scholar

Odekerken, V.J., van Laar, T., Staal, M.J., Mosch, A., Hoffmann, C.F., Nijssen, P.C., Beute, G.N., van Vugt, J.P., Lenders, M.W., Contarino, M.F., et al. (2013) Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for advanced Parkinson’s disease (NSTAPS study): a randomised controlled trial. Lancet Neurol. 12, 37–44.10.1016/S1474-4422(12)70264-8Search in Google Scholar

Parent, A. and Hazrati, L.N. (1995). Functional anatomy of the basal ganglia. II. The place of subthalamic nucleus and external pallidum in basal ganglia circuitry. Brain Res. Brain Res. Rev. 20, 128–154.10.1016/0165-0173(94)00008-DSearch in Google Scholar

Parent, M., Wallman, M.J., and Descarries, L. (2010). Distribution and ultrastructural features of the serotonin innervation in rat and squirrel monkey subthalamic nucleus. Eur. J. Neurosci. 31, 1233–1242.10.1111/j.1460-9568.2010.07143.xSearch in Google Scholar

Parent, M., Wallman, M.J., Gagnon, D., and Parent. A. (2011). Serotonin innervation of basal ganglia in monkeys and humans. J. Chem. Neuroanat. 41, 256–265.10.1016/j.jchemneu.2011.04.005Search in Google Scholar

Perlmutter, J.S. and Mink, J.W. (2006). Deep brain stimulation. Annu. Rev. Neurosci. 29, 229–257.10.1146/annurev.neuro.29.051605.112824Search in Google Scholar

Pompeiano, M., Palacios, J.M., and Mengod, G. (1994). Distribution of the serotonin 5-HT2 receptor family mRNAs: comparison between 5-HT2A and 5-HT2C receptors. Brain Res. Mol. Brain Res. 23, 163–178.10.1016/0169-328X(94)90223-2Search in Google Scholar

Riad, M., Garcia, S., Watkins, K.C., Jodoin, N., Doucet, E., Langlois, X., el Mestikawy, S., Hamon, M., and Descarries, L. (2000). Somatodendritic localization of 5-HT1A and preterminal axonal localization of 5-HT1B serotonin receptors in adult rat brain. J. Comp. Neurol. 417, 181–194.10.1002/(SICI)1096-9861(20000207)417:2<181::AID-CNE4>3.0.CO;2-ASearch in Google Scholar

Sano, H., Chiken, S., Hikida, T., Kobayashi, K., and Nambu, A. (2013). Signals through the striatopallidal indirect pathway stop movements by phasic excitation in the substantia nigra. J. Neurosci. 33, 7583–7594.10.1523/JNEUROSCI.4932-12.2013Search in Google Scholar

Sari, Y. (2004). Serotonin1B receptors: from protein to physiological function and behavior. Neurosci. Biobehav. Rev. 28, 565–582.10.1016/j.neubiorev.2004.08.008Search in Google Scholar

Sari, Y., Miquel, M.C., Brisorgueil, M.J., Ruiz, G., Doucet, E., Hamon, M., and Vergé, D. (1999). Cellular and subcellular localization of 5-hydroxytryptamine1B receptors in the rat central nervous system: immunocytochemical, autoradiographic and lesion studies. Neuroscience 88, 899–915.10.1016/S0306-4522(98)00256-5Search in Google Scholar

Sato, F., Parent, M., Levesque, M., and Parent, A. (2000). Axonal branching pattern of neurons of the subthalamic nucleus in primates. J. Comp. Neurol. 424, 142–152.10.1002/1096-9861(20000814)424:1<142::AID-CNE10>3.0.CO;2-8Search in Google Scholar

Setola, V., Hufeisen, S.J., Grande-Allen, K.J., Vesely, I., Glennon, R.A., Blough, B., Rothman, R.B., and Roth, B.L. (2003). 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitro. Mol. Pharmacol. 63, 1223–1229.10.1124/mol.63.6.1223Search in Google Scholar

Shen, K.Z. and Johnson, S.W. (2006). Subthalamic stimulation evokes complex EPSCs in the rat substantia nigra pars reticulata in vitro. J. Physiol. 573, 697–709.10.1113/jphysiol.2006.110031Search in Google Scholar

Shen, K.Z. and Johnson, S.W. (2008). 5-HT inhibits synaptic transmission in rat subthalamic nucleus neurons in vitro. Neuroscience 151, 1029–1033.10.1016/j.neuroscience.2007.12.001Search in Google Scholar

Shen, K.Z., Kozell, L.B., and Johnson, S.W. (2007) Multiple conductances are modulated by 5-HT receptor subtypes in rat subthalamic nucleus neurons. Neuroscience 148, 996–1003.10.1016/j.neuroscience.2007.07.012Search in Google Scholar

Smith, Y. and Parent, A. (1988). Neurons of the subthalamic nucleus in primates display glutamate but not GABA immunoreactivity. Brain Res. 453, 353–356.10.1016/0006-8993(88)90177-1Search in Google Scholar

Stanford, I.M. and Lacey, M.G. (1996). Differential actions of serotonin, mediated by 5-HT1B and 5-HT2C receptors, on GABA-mediated synaptic input to rat substantia nigra pars reticulata neurons in vitro. J. Neurosci. 16, 7566–7573.10.1523/JNEUROSCI.16-23-07566.1996Search in Google Scholar

Stanford, I.M., Kantaria, M.A., Chahal, H.S., Loucif, K.C., and Wilson, C.L. (2005). 5-Hydroxytryptamine induced excitation and inhibition in the subthalamic nucleus: action at 5-HT(2C), 5-HT(4) and 5-HT(1A) receptors. Neuropharmacology 49, 1228–1234.10.1016/j.neuropharm.2005.09.003Search in Google Scholar

Steigerwald, F., Pötter, M., Herzog, J., Pinsker, M., Kopper, F., Mehdorn, H., Deuschl, G., and Volkmann, J. (2008). Neuronal activity of the human subthalamic nucleus in the parkinsonian and nonparkinsonian state. J. Neurophysiol. 100, 2515–2524.10.1152/jn.90574.2008Search in Google Scholar

Steinbusch, H.W. (1981). Distribution of serotonin-immunoreactivity in the central nervous system of the rat-cell bodies and terminals. Neuroscience 6, 557–618.10.1016/0306-4522(81)90146-9Search in Google Scholar

Steininger, T.L., Wainer, B.H., Blakely, R.D., and Rye, D.B. (1997). Serotonergic dorsal raphe nucleus projections to the cholinergic and noncholinergic neurons of the pedunculopontine tegmental region: a light and electron microscopic anterograde tracing and immunohistochemical study. J. Comp. Neurol. 382, 302–322.10.1002/(SICI)1096-9861(19970609)382:3<302::AID-CNE2>3.0.CO;2-7Search in Google Scholar

Tan, S.K., Hartung, H., Visser-Vandewalle, V., Steinbusch, H.W., Temel, Y., and Sharp, T. (2012). A combined in vivo neurochemical and electrophysiological analysis of the effect of high-frequency stimulation of the subthalamic nucleus on 5-HT transmission. Exp. Neurol. 233, 145–153.10.1016/j.expneurol.2011.08.027Search in Google Scholar

Temel, Y., Boothman, L.J., Blokland, A., Magill, P.J., Steinbusch, H.W., Visser-Vandewalle, V., and Sharp, T. (2007). Inhibition of 5-HT neuron activity and induction of depressive-like behavior by high-frequency stimulation of the subthalamic nucleus. Proc. Natl. Acad. Sci. USA 104, 17087–17092.10.1073/pnas.0704144104Search in Google Scholar

Torres, G.E., Gainetdinov, R.R., and Caron, M.G. (2003). Plasma membrane monoamine transporters: structure, regulation and function. Nat. Rev. Neurosci. 4, 13–25.10.1038/nrn1008Search in Google Scholar

Urbain, N., Rentéro, N., Gervasoni, D., Renaud, B., and Chouvet, G. The switch of subthalamic neurons from an irregular to a bursting pattern does not solely depend on their GABAergic inputs in the anesthetic-free rat. J. Neurosci. 22, 8665–8675.10.1523/JNEUROSCI.22-19-08665.2002Search in Google Scholar

Van Bockstaele, E.J., Cestari, D.M., and Pickel V.M. (1994). Synaptic structure and connectivity of serotonin terminals in the ventral tegmental area: potential sites for modulation of mesolimbic dopamine neurons. Brain Res. 647, 307–322.10.1016/0006-8993(94)91330-7Search in Google Scholar

Van Bockstaele, E.J., Chan, J., and Pickel, V.M. (1996). Pre- and postsynaptic sites for serotonin modulation of GABA-containing neurons in the shell region of the rat nucleus accumbens. J. Comp. Neurol. 371, 116–128.10.1002/(SICI)1096-9861(19960715)371:1<116::AID-CNE7>3.0.CO;2-6Search in Google Scholar

Vilaró, M.T., Cortés, R., and Mengod, G. (2005). Serotonin 5-HT4 receptors and their mRNAs in rat and guinea pig brain: distribution and effects of neurotoxic lesions. J. Comp. Neurol. 484, 418–439.10.1002/cne.20447Search in Google Scholar

Voigt, M.M., Laurie, D.J., Seeburg, P.H., and Bach, A. (1991) Molecular cloning and characterization of a rat brain cDNA encoding a 5-hydroxytryptamine1B receptor. EMBO J. 10, 4017–4023.10.1002/j.1460-2075.1991.tb04977.xSearch in Google Scholar

Walker, H.C., Huang, H., Gonzalez, C.L., Bryant, J.E., Killen, J., Cutter, G.R., Knowlton, R.C., Montgomery, E.B., Guthrie, B.L., and Watts, R.L. (2012). Short latency activation of cortex during clinically effective subthalamic deep brain stimulation for Parkinson’s disease. Mov Disord. 27, 864–873.10.1002/mds.25025Search in Google Scholar

Wallman, M.J., Gagnon, D., and Parent, M. (2011). Serotonin innervation of human basal ganglia. Eur. J. Neurosci. 33, 1519–1532.10.1111/j.1460-9568.2011.07621.xSearch in Google Scholar

Walters, J.R., Hu, D., Itoga, C.A., Parr-Brownlie, L.C., and Bergstrom, D.A. (2007). Phase relationships support a role for coordinated activity in the indirect pathway in organizing slow oscillations in basal ganglia output after loss of dopamine. Neuroscience 144, 762–776.10.1016/j.neuroscience.2006.10.006Search in Google Scholar PubMed PubMed Central

Wichmann, T. and Dostrovsky, J.O. (2011) Pathological basal ganglia activity in movement disorders. Neuroscience 198, 232–244.10.1016/j.neuroscience.2011.06.048Search in Google Scholar PubMed PubMed Central

Wichmann, T., Bergman, H., and DeLong, M.R. (1994). The primate subthalamic nucleus. I. Functional properties in intact animals. J. Neurophysiol. 72, 494–506.10.1152/jn.1994.72.2.494Search in Google Scholar PubMed

Wilson, C.J. and Bevan, M.D. (2011). Intrinsic dynamics and synaptic inputs control the activity patterns of subthalamic nucleus neurons in health and in Parkinson’s disease. Neuroscience. 198, 54–68.10.1016/j.neuroscience.2011.06.049Search in Google Scholar PubMed PubMed Central

Wright, D.E., Seroogy, K.B., Lundgren, K.H., Davis, B.M., and Jennes, L. (1995). Comparative localization of serotonin1A, 1C, and 2 receptor subtype mRNAs in rat brain. J. Comp. Neurol. 351, 357–373.10.1002/cne.903510304Search in Google Scholar PubMed

Xiang, Z., Wang, L., and Kitai, S.T. (2005). Modulation of spontaneous firing in rat subthalamic neurons by 5-HT receptor subtypes. J. Neurophysiol. 93, 1145–1157.10.1152/jn.00561.2004Search in Google Scholar PubMed

Zhou, F.M. and Lee, C.R. (2011). Intrinsic and integrative properties of substantia nigra pars reticulata neurons. Neuroscience 198, 69–94.10.1016/j.neuroscience.2011.07.061Search in Google Scholar PubMed PubMed Central

Zhou, F.W., Matta, S.G., and Zhou, F.M. (2008). Constitutively active TRPC3 channels regulate basal ganglia output neurons. J. Neurosci. 28, 473–482.10.1523/JNEUROSCI.3978-07.2008Search in Google Scholar PubMed PubMed Central

Received: 2014-1-7
Accepted: 2014-3-4
Published Online: 2014-4-9
Published in Print: 2014-8-1

© 2014 by De Gruyter

Scroll Up Arrow