Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter July 22, 2014

Optogenetic studies of nicotinic contributions to cholinergic signaling in the central nervous system

  • Li Jiang EMAIL logo , Gretchen Y. López-Hernández , James Lederman , David A. Talmage and Lorna W. Role


Molecular manipulations and targeted pharmacological studies provide a compelling picture of which nicotinic receptor subtypes are where in the central nervous system (CNS) and what happens if one activates or deletes them. However, understanding the physiological contribution of nicotinic receptors to endogenous acetylcholine (ACh) signaling in the CNS has proven a more difficult problem to solve. In this review, we provide a synopsis of the literature on the use of optogenetic approaches to control the excitability of cholinergic neurons and to examine the role of CNS nicotinic ACh receptors (nAChRs). As is often the case, this relatively new technology has answered some questions and raised others. Overall, we believe that optogenetic manipulation of cholinergic excitability in combination with some rigorous pharmacology will ultimately advance our understanding of the many functions of nAChRs in the brain.

Corresponding author: Li Jiang, Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, NY 11794, USA, e-mail: ; and Center for Nervous System Disorders, Stony Brook University, Stony Brook, NY 11794, USA,


Akabas, M.H., Stauffer, D.A., Xu, M., and Karlin, A. (1992). Acetylcholine receptor channel structure probed in cysteine-substitution mutants. Science 258, 307–310.10.1126/science.1384130Search in Google Scholar

Alkondon, M., Pereira, E.F., and Albuquerque, E.X. (1998). a-bungarotoxin- and methyllycaconitine-sensitive nicotinic receptors mediate fast synaptic transmission in interneurons of rat hippocampal slices. Brain Res. 810, 257–263.10.1016/S0006-8993(98)00880-4Search in Google Scholar

Allen, T.G., Abogadie, F.C., and Brown, D.A. (2006). Simultaneous release of glutamate and acetylcholine from single magnocellular “cholinergic” basal forebrain neurons. J. Neurosci. 26, 1588–1595.10.1523/JNEUROSCI.3979-05.2006Search in Google Scholar PubMed PubMed Central

Andrasfalvy, B.K., Zemelman, B.V., Tang, J., and Vaziri, A. (2010). Two-photon single-cell optogenetic control of neuronal activity by sculpted light. Proc. Natl. Acad. Sci. USA 107, 11981–11986.10.1073/pnas.1006620107Search in Google Scholar PubMed PubMed Central

Anikeeva, P., Andalman, A.S., Witten, I., Warden, M., Goshen, I., Grosenick, L., Gunaydin, L.A., Frank, L.M., and Deisseroth, K. (2012). Optetrode: a multichannel readout for optogenetic control in freely moving mice. Nat. Neurosci. 15, 163–170.10.1038/nn.2992Search in Google Scholar PubMed PubMed Central

Aosaki, T., Graybiel, A.M., and Kimura, M. (1994). Effect of the nigrostriatal dopamine system on acquired neural responses in the striatum of behaving monkeys. Science 265, 412–415.10.1126/science.8023166Search in Google Scholar PubMed

Aravanis, A.M., Wang, L.P., Zhang, F., Meltzer, L.A., Mogri, M.Z., Schneider, M.B., and Deisseroth, K. (2007). An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology. J. Neural Eng. 4, S143–S156.Search in Google Scholar

Arias, H.R. (2010). Positive and negative modulation of nicotinic receptors. Adv. Protein Chem. Struct. Biol. 80, 153–203.10.1016/B978-0-12-381264-3.00005-9Search in Google Scholar PubMed

Arroyo, S., Bennett, C., Aziz, D., Brown, S.P., and Hestrin, S. (2012). Prolonged disynaptic inhibition in the cortex mediated by slow, non-a7 nicotinic excitation of a specific subset of cortical interneurons. J. Neurosci. 32, 3859–3864.10.1523/JNEUROSCI.0115-12.2012Search in Google Scholar PubMed PubMed Central

Arroyo, S., Bennett, C., and Hestrin, S. (2014). Nicotinic modulation of cortical circuits. Front. Neural Circuits 8, 30.10.3389/fncir.2014.00030Search in Google Scholar PubMed PubMed Central

Avena, N.M. and Rada, P.V. (2012). Cholinergic modulation of food and drug satiety and withdrawal. Physiol. Behav. 106, 332–336.10.1016/j.physbeh.2012.03.020Search in Google Scholar PubMed PubMed Central

Bartfai, T., Iverfeldt, K., Fisone, G., and Serfozo, P. (1988). Regulation of the release of coexisting neurotransmitters. Annu. Rev. Pharmacol. Toxicol. 28, 285–310.10.1146/ in Google Scholar

Bell, K.A., Shim, H., Chen, C.K., and McQuiston, A.R. (2011). Nicotinic excitatory postsynaptic potentials in hippocampal CA1 interneurons are predominantly mediated by nicotinic receptors that contain a4 and b2 subunits. Neuropharmacology 61, 1379–1388.10.1016/j.neuropharm.2011.08.024Search in Google Scholar

Bell, L.A., Bell, K.A., and McQuiston, A.R. (2013). Synaptic muscarinic response types in hippocampal CA1 interneurons depend on different levels of presynaptic activity and different muscarinic receptor subtypes. Neuropharmacology 73, 160–173.10.1016/j.neuropharm.2013.05.026Search in Google Scholar

Benardo, L.S. (1991). Acetylcholine and norepinephrine mediate slow synaptic potentials in normal and epileptic neocortex. Neurosci. Lett. 126, 137–140.10.1016/0304-3940(91)90538-5Search in Google Scholar

Berg, D.K. (2011). Timing is everything, even for cholinergic control. Neuron 71, 6–8.10.1016/j.neuron.2011.06.029Search in Google Scholar PubMed PubMed Central

Bernstein, J.G., Han, X., Henninger, M.A., Ko, E.Y., Qian, X., Franzesi, G.T., McConnell, J.P., Stern, P., Desimone, R., and Boyden, E.S. (2008). Prosthetic systems for therapeutic optical activation and silencing of genetically-targeted neurons. Proc. Soc. Photo. Opt. Instrum. Eng. 6854, 68540H.10.1117/12.768798Search in Google Scholar PubMed PubMed Central

Boyden, E.S., Zhang, F., Bamberg, E., Nagel, G., and Deisseroth, K. (2005). Millisecond-timescale, genetically targeted optical control of neural activity. Nat. Neurosci. 8, 1263–1268.10.1038/nn1525Search in Google Scholar PubMed

Britt, J.P. and McGehee, D.S. (2008). Presynaptic opioid and nicotinic receptor modulation of dopamine overflow in the nucleus accumbens. J. Neurosci. 28, 1672–1681.10.1523/JNEUROSCI.4275-07.2008Search in Google Scholar PubMed PubMed Central

Brown, D.A. (2010). Muscarinic acetylcholine receptors (mAChRs) in the nervous system: some functions and mechanisms. J. Mol. Neurosci. 41, 340–346.10.1007/s12031-010-9377-2Search in Google Scholar PubMed

Brown, M.T., Tan, K.R., O’Connor, E.C., Nikonenko, I., Muller, D., and Luscher, C. (2012). Ventral tegmental area GABA projections pause accumbal cholinergic interneurons to enhance associative learning. Nature 492, 452–456.10.1038/nature11657Search in Google Scholar PubMed

Cachope, R., Mateo, Y., Mathur, B.N., Irving, J., Wang, H.L., Morales, M., Lovinger, D.M., and Cheer, J.F. (2012). Selective activation of cholinergic interneurons enhances accumbal phasic dopamine release: setting the tone for reward processing. Cell Rep. 2, 33–41.10.1016/j.celrep.2012.05.011Search in Google Scholar

Changeux, J.P. (2010). Nicotine addiction and nicotinic receptors: lessons from genetically modified mice. Nat. Rev. Neurosci. 11, 389–401.10.1038/nrn2849Search in Google Scholar

Chuhma, N., Mingote, S., Moore, H., and Rayport, S. (2014). Dopamine neurons control striatal cholinergic neurons via regionally heterogeneous dopamine and glutamate signaling. Neuron 81, 901–912.10.1016/j.neuron.2013.12.027Search in Google Scholar

Clementi, F., Fornasari, D., and Gotti, C. (2000). Neuronal nicotinic receptors, important new players in brain function. Eur. J. Pharmacol. 393, 3–10.10.1016/S0014-2999(00)00066-2Search in Google Scholar

Cragg, S.J. (2006). Meaningful silences: how dopamine listens to the ACh pause. Trends Neurosci. 29, 125–131.10.1016/j.tins.2006.01.003Search in Google Scholar

Cruikshank, S.J., Urabe, H., Nurmikko, A.V., and Connors, B.W. (2010). Pathway-specific feedforward circuits between thalamus and neocortex revealed by selective optical stimulation of axons. Neuron 65, 230–245.10.1016/j.neuron.2009.12.025Search in Google Scholar

Dani, J.A. (2001). Overview of nicotinic receptors and their roles in the central nervous system. Biol. Psychiatry 49, 166–174.10.1016/S0006-3223(00)01011-8Search in Google Scholar

Dani, J.A. and Bertrand, D. (2007). Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system. Annu. Rev. Pharmacol. Toxicol. 47, 699–729.10.1146/annurev.pharmtox.47.120505.105214Search in Google Scholar PubMed

Deisseroth, K. (2011). Optogenetics. Nat. Methods 8, 26–29.10.1038/nmeth.f.324Search in Google Scholar PubMed PubMed Central

Ding, J.B., Guzman, J.N., Peterson, J.D., Goldberg, J.A., and Surmeier, D.J. (2010). Thalamic gating of corticostriatal signaling by cholinergic interneurons. Neuron 67, 294–307.10.1016/j.neuron.2010.06.017Search in Google Scholar PubMed PubMed Central

Docherty, M., Bradford, H.F., and Wu, J.Y. (1987). Co-release of glutamate and aspartate from cholinergic and GABAergic synaptosomes. Nature 330, 64–66.10.1038/330064a0Search in Google Scholar PubMed

Drever, B.D., Riedel, G., and Platt, B. (2011). The cholinergic system and hippocampal plasticity. Behav. Brain Res. 221, 505–514.10.1016/j.bbr.2010.11.037Search in Google Scholar PubMed

Dunant, Y., Bancila, V., and Cordeiro, M. (2010). Ultra-fast versus sustained cholinergic transmission: a variety of different mechanisms. J. Mol. Neurosci. 40, 27–31.10.1007/s12031-009-9249-9Search in Google Scholar PubMed

Eckenstein, F. and Baughman, R.W. (1984). Two types of cholinergic innervation in cortex, one co-localized with vasoactive intestinal polypeptide. Nature 309, 153–155.10.1038/309153a0Search in Google Scholar PubMed

El Mestikawy, S., Wallen-Mackenzie, A., Fortin, G.M., Descarries, L., and Trudeau, L.E. (2011). From glutamate co-release to vesicular synergy: vesicular glutamate transporters. Nat. Rev. Neurosci. 12, 204–216.10.1038/nrn2969Search in Google Scholar PubMed

English, D.F., Ibanez-Sandoval, O., Stark, E., Tecuapetla, F., Buzsaki, G., Deisseroth, K., Tepper, J.M., and Koos, T. (2012). GABAergic circuits mediate the reinforcement-related signals of striatal cholinergic interneurons. Nat. Neurosci. 15, 123–130.10.1038/nn.2984Search in Google Scholar PubMed PubMed Central

Exley, R. and Cragg, S.J. (2008). Presynaptic nicotinic receptors: a dynamic and diverse cholinergic filter of striatal dopamine neurotransmission. Br. J. Pharmacol. 153 Suppl 1, S283–S297.10.1038/sj.bjp.0707510Search in Google Scholar PubMed PubMed Central

Fenno, L., Yizhar, O., and Deisseroth, K. (2011). The development and application of optogenetics. Annu. Rev. Neurosci. 34, 389–412.10.1146/annurev-neuro-061010-113817Search in Google Scholar PubMed PubMed Central

Frazier, C.J., Buhler, A.V., Weiner, J.L., and Dunwiddie, T.V. (1998). Synaptic potentials mediated via a-bungarotoxin-sensitive nicotinic acetylcholine receptors in rat hippocampal interneurons. J. Neurosci. 18, 8228–8235.10.1523/JNEUROSCI.18-20-08228.1998Search in Google Scholar

Gay, E.A. and Yakel, J.L. (2007). Gating of nicotinic ACh receptors; new insights into structural transitions triggered by agonist binding that induce channel opening. J. Physiol. 584, 727–733.10.1113/jphysiol.2007.142554Search in Google Scholar PubMed PubMed Central

Giessel, A.J. and Sabatini, B.L. (2010). M1 muscarinic receptors boost synaptic potentials and calcium influx in dendritic spines by inhibiting postsynaptic SK channels. Neuron 68, 936–947.10.1016/j.neuron.2010.09.004Search in Google Scholar PubMed PubMed Central

Giniatullin, R., Nistri, A., and Yakel, J.L. (2005). Desensitization of nicotinic ACh receptors: shaping cholinergic signaling. Trends Neurosci. 28, 371–378.10.1016/j.tins.2005.04.009Search in Google Scholar PubMed

Girod, R., Crabtree, G., Ernstrom, G., Ramirez-Latorre, J., McGehee, D., Turner, J., and Role, L. (1999). Heteromeric complexes of a 5 and/or a 7 subunits. Effects of calcium and potential role in nicotine-induced presynaptic facilitation. Ann. NY Acad. Sci. 868, 578–590.10.1111/j.1749-6632.1999.tb11331.xSearch in Google Scholar PubMed

Gonzalez-Reyes, L.E., Verbitsky, M., Blesa, J., Jackson-Lewis, V., Paredes, D., Tillack, K., Phani, S., Kramer, E.R., Przedborski, S., and Kottmann, A.H. (2012). Sonic hedgehog maintains cellular and neurochemical homeostasis in the adult nigrostriatal circuit. Neuron 75, 306–319.10.1016/j.neuron.2012.05.018Search in Google Scholar PubMed PubMed Central

Gras, C., Amilhon, B., Lepicard, E.M., Poirel, O., Vinatier, J., Herbin, M., Dumas, S., Tzavara, E.T., Wade, M.R., Nomikos, G.G., et al. (2008). The vesicular glutamate transporter VGLUT3 synergizes striatal acetylcholine tone. Nat. Neurosci. 11, 292–300.10.1038/nn2052Search in Google Scholar PubMed

Gray, R., Rajan, A.S., Radcliffe, K.A., Yakehiro, M., and Dani, J.A. (1996). Hippocampal synaptic transmission enhanced by low concentrations of nicotine. Nature 383, 713–716.10.1038/383713a0Search in Google Scholar PubMed

Grybko, M.J., Hahm, E.T., Perrine, W., Parnes, J.A., Chick, W.S., Sharma, G., Finger, T.E., and Vijayaraghavan, S. (2011). A transgenic mouse model reveals fast nicotinic transmission in hippocampal pyramidal neurons. Eur. J. Neurosci. 33, 1786–1798.10.1111/j.1460-9568.2011.07671.xSearch in Google Scholar PubMed PubMed Central

Gu, Z. and Yakel, J.L. (2011). Timing-dependent septal cholinergic induction of dynamic hippocampal synaptic plasticity. Neuron 71, 155–165.10.1016/j.neuron.2011.04.026Search in Google Scholar PubMed PubMed Central

Gu, Z., Lamb, P.W., and Yakel, J.L. (2012). Cholinergic coordination of presynaptic and postsynaptic activity induces timing-dependent hippocampal synaptic plasticity. J. Neurosci. 32, 12337–12348.10.1523/JNEUROSCI.2129-12.2012Search in Google Scholar PubMed PubMed Central

Guzman, M.S., De Jaeger, X., Raulic, S., Souza, I.A., Li, A.X., Schmid, S., Menon, R.S., Gainetdinov, R.R., Caron, M.G., Bartha, R., et al. (2011). Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission. PLoS Biol. 9, e1001194.10.1371/journal.pbio.1001194Search in Google Scholar PubMed PubMed Central

Guzman, M.S., De Jaeger, X., Drangova, M., Prado, M.A., Gros, R., and Prado, V.F. (2013). Mice with selective elimination of striatal acetylcholine release are lean, show altered energy homeostasis and changed sleep/wake cycle. J. Neurochem. 124, 658–669.10.1111/jnc.12128Search in Google Scholar

Hasselmo, M.E. and Sarter, M. (2011). Modes and models of forebrain cholinergic neuromodulation of cognition. Neuropsychopharmacology 36, 52–73.10.1038/npp.2010.104Search in Google Scholar

Henny, P. and Jones, B.E. (2008). Projections from basal forebrain to prefrontal cortex comprise cholinergic, GABAergic and glutamatergic inputs to pyramidal cells or interneurons. Eur. J. Neurosci. 27, 654–670.10.1111/j.1460-9568.2008.06029.xSearch in Google Scholar

Higley, M.J., Soler-Llavina, G.J., and Sabatini, B.L. (2009). Cholinergic modulation of multivesicular release regulates striatal synaptic potency and integration. Nat. Neurosci. 12, 1121–1128.10.1038/nn.2368Search in Google Scholar

Higley, M.J., Gittis, A.H., Oldenburg, I.A., Balthasar, N., Seal, R.P., Edwards, R.H., Lowell, B.B., Kreitzer, A.C., and Sabatini, B.L. (2011). Cholinergic interneurons mediate fast VGluT3-dependent glutamatergic transmission in the striatum. PLoS One 6, e19155.10.1371/journal.pone.0019155Search in Google Scholar

Hnasko, T.S. and Edwards, R.H. (2012). Neurotransmitter corelease: mechanism and physiological role. Annu. Rev. Physiol. 74, 225–243.10.1146/annurev-physiol-020911-153315Search in Google Scholar

Huh, K.H. and Fuhrer, C. (2002). Clustering of nicotinic acetylcholine receptors: from the neuromuscular junction to interneuronal synapses. Mol. Neurobiol. 25, 79–112.10.1385/MN:25:1:079Search in Google Scholar

Huh, C.Y., Danik, M., Manseau, F., Trudeau, L.E., and Williams, S. (2008). Chronic exposure to nerve growth factor increases acetylcholine and glutamate release from cholinergic neurons of the rat medial septum and diagonal band of Broca via mechanisms mediated by p75NTR. J. Neurosci. 28, 1404–1409.10.1523/JNEUROSCI.4851-07.2008Search in Google Scholar PubMed PubMed Central

Jensen, A.A., Frolund, B., Liljefors, T., and Krogsgaard-Larsen, P. (2005). Neuronal nicotinic acetylcholine receptors: structural revelations, target identifications, and therapeutic inspirations. J. Med. Chem. 48, 4705–4745.10.1021/jm040219eSearch in Google Scholar PubMed

Jiang, L. and Role, L.W. (2008). Facilitation of cortico-amygdala synapses by nicotine: activity-dependent modulation of glutamatergic transmission. J. Neurophysiol. 99, 1988–1999.10.1152/jn.00933.2007Search in Google Scholar PubMed PubMed Central

Jo, Y.H., Wiedl, D., and Role, L.W. (2005). Cholinergic modulation of appetite-related synapses in mouse lateral hypothalamic slice. J. Neurosci. 25, 11133–11144.10.1523/JNEUROSCI.3638-05.2005Search in Google Scholar

Jones, S. and Yakel, J.L. (1997). Functional nicotinic ACh receptors on interneurones in the rat hippocampus. J. Physiol. 504, 603–610.10.1111/j.1469-7793.1997.603bd.xSearch in Google Scholar

Jones, S., Sudweeks, S., and Yakel, J.L. (1999). Nicotinic receptors in the brain: correlating physiology with function. Trends Neurosci. 22, 555–561.10.1016/S0166-2236(99)01471-XSearch in Google Scholar

Joshua, M., Adler, A., Mitelman, R., Vaadia, E., and Bergman, H. (2008). Midbrain dopaminergic neurons and striatal cholinergic interneurons encode the difference between reward and aversive events at different epochs of probabilistic classical conditioning trials. J. Neurosci. 28, 11673–11684.10.1523/JNEUROSCI.3839-08.2008Search in Google Scholar PubMed PubMed Central

Kalmbach, A., Hedrick, T., and Waters, J. (2012). Selective optogenetic stimulation of cholinergic axons in neocortex. J. Neurophysiol. 107, 2008–2019.10.1152/jn.00870.2011Search in Google Scholar PubMed PubMed Central

Karlin, A. (2002). Emerging structure of the nicotinic acetylcholine receptors. Nat. Rev. Neurosci. 3, 102–114.10.1038/nrn731Search in Google Scholar PubMed

Kenney, J.W., Raybuck, J.D., and Gould, T.J. (2012). Nicotinic receptors in the dorsal and ventral hippocampus differentially modulate contextual fear conditioning. Hippocampus 22, 1681–1690.10.1002/hipo.22003Search in Google Scholar PubMed PubMed Central

Khiroug, L., Giniatullin, R., Klein, R.C., Fayuk, D., and Yakel, J.L. (2003). Functional mapping and Ca2+ regulation of nicotinic acetylcholine receptor channels in rat hippocampal CA1 neurons. J. Neurosci. 23, 9024–9031.10.1523/JNEUROSCI.23-27-09024.2003Search in Google Scholar

Klein, R.C. and Yakel, J.L. (2006). Functional somato-dendritic a7-containing nicotinic acetylcholine receptors in the rat basolateral amygdala complex. J. Physiol. 576, 865–872.10.1113/jphysiol.2006.118232Search in Google Scholar PubMed PubMed Central

Kolisnyk, B., Guzman, M.S., Raulic, S., Fan, J., Magalhaes, A.C., Feng, G., Gros, R., Prado, V.F., and Prado, M.A. (2013). ChAT-ChR2-EYFP mice have enhanced motor endurance but show deficits in attention and several additional cognitive domains. J. Neurosci. 33, 10427–10438.10.1523/JNEUROSCI.0395-13.2013Search in Google Scholar PubMed PubMed Central

Koos, T. and Tepper, J.M. (2002). Dual cholinergic control of fast-spiking interneurons in the neostriatum. J. Neurosci. 22, 529–535.10.1523/JNEUROSCI.22-02-00529.2002Search in Google Scholar

Langley, J.N. (1905). On the reaction of cells and of nerve-endings to certain poisons, chiefly as regards the reaction of striated muscle to nicotine and to curari. J. Physiol. 33, 374–413.10.1113/jphysiol.1905.sp001128Search in Google Scholar PubMed PubMed Central

Lee, S., Kim, K., and Zhou, Z.J. (2010). Role of ACh-GABA cotransmission in detecting image motion and motion direction. Neuron 68, 1159–1172.10.1016/j.neuron.2010.11.031Search in Google Scholar PubMed PubMed Central

Lester, H.A., Dibas, M.I., Dahan, D.S., Leite, J.F., and Dougherty, D.A. (2004). Cys-loop receptors: new twists and turns. Trends Neurosci. 27, 329–336.10.1016/j.tins.2004.04.002Search in Google Scholar PubMed

Letzkus, J.J., Wolff, S.B., Meyer, E.M., Tovote, P., Courtin, J., Herry, C., and Luthi, A. (2011). A disinhibitory microcircuit for associative fear learning in the auditory cortex. Nature 480, 331–335.10.1038/nature10674Search in Google Scholar PubMed

Li, S., Cullen, W.K., Anwyl, R., and Rowan, M.J. (2007). Muscarinic acetylcholine receptor-dependent induction of persistent synaptic enhancement in rat hippocampus in vivo. Neuroscience 144, 754–761.10.1016/j.neuroscience.2006.10.001Search in Google Scholar PubMed

Lima, R.H., Radiske, A., Kohler, C.A., Gonzalez, M.C., Bevilaqua, L.R., Rossato, J.I., Medina, J.H., and Cammarota, M. (2013). Nicotine modulates the long-lasting storage of fear memory. Learn. Mem. 20, 120–124.10.1101/lm.029900.112Search in Google Scholar PubMed

Lin, J.Y. (2011). A user’s guide to channelrhodopsin variants: features, limitations and future developments. Exp. Physiol. 96, 19–25.10.1113/expphysiol.2009.051961Search in Google Scholar PubMed PubMed Central

Lin, J.Y., Lin, M.Z., Steinbach, P., and Tsien, R.Y. (2009). Characterization of engineered channelrhodopsin variants with improved properties and kinetics. Biophys. J. 96, 1803–1814.10.1016/j.bpj.2008.11.034Search in Google Scholar PubMed PubMed Central

Lin, J.Y., Knutsen, P.M., Muller, A., Kleinfeld, D., and Tsien, R.Y. (2013). ReaChR: a red-shifted variant of channelrhodopsin enables deep transcranial optogenetic excitation. Nat. Neurosci. 16, 1499–1508.10.1038/nn.3502Search in Google Scholar PubMed PubMed Central

Liu, T., Fujita, T., and Kumamoto, E. (2011). Acetylcholine and norepinephrine mediate GABAergic but not glycinergic transmission enhancement by melittin in adult rat substantia gelatinosa neurons. J. Neurophysiol. 106, 233–246.10.1152/jn.00838.2010Search in Google Scholar

Loewi, O. (1921). Über humorale Übertragbarkeit der Herznervenwirkung. I. Pflugers Arch. 189, 239–242.10.1007/BF01738910Search in Google Scholar

Ma, M. and Luo, M. (2012). Optogenetic activation of basal forebrain cholinergic neurons modulates neuronal excitability and sensory responses in the main olfactory bulb. J. Neurosci. 32, 10105–10116.10.1523/JNEUROSCI.0058-12.2012Search in Google Scholar

MacDermott, A.B., Role, L.W., and Siegelbaum, S.A. (1999). Presynaptic ionotropic receptors and the control of transmitter release. Annu. Rev. Neurosci. 22, 443–485.10.1146/annurev.neuro.22.1.443Search in Google Scholar

Madisen, L., Mao, T., Koch, H., Zhuo, J.M., Berenyi, A., Fujisawa, S., Hsu, Y.W., Garcia, A,J. 3rd, Gu, X., Zanella, S., et al. (2012). A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing. Nat. Neurosci. 15, 793–802.10.1038/nn.3078Search in Google Scholar

Manns, I.D., Mainville, L., and Jones, B.E. (2001). Evidence for glutamate, in addition to acetylcholine and GABA, neurotransmitter synthesis in basal forebrain neurons projecting to the entorhinal cortex. Neuroscience 107, 249–263.10.1016/S0306-4522(01)00302-5Search in Google Scholar

Mansvelder, H.D. and McGehee, D.S. (2000). Long-term potentiation of excitatory inputs to brain reward areas by nicotine. Neuron 27, 349–357.10.1016/S0896-6273(00)00042-8Search in Google Scholar

Marchi, M. and Grilli, M. (2010). Presynaptic nicotinic receptors modulating neurotransmitter release in the central nervous system: functional interactions with other coexisting receptors. Prog. Neurobiol. 92, 105–111.10.1016/j.pneurobio.2010.06.004Search in Google Scholar

Mark, G.P., Shabani, S., Dobbs, L.K., and Hansen, S.T. (2011). Cholinergic modulation of mesolimbic dopamine function and reward. Physiol. Behav. 104, 76–81.10.1016/j.physbeh.2011.04.052Search in Google Scholar

McGehee, D.S. and Role, L.W. (1996). Presynaptic ionotropic receptors. Curr. Opin. Neurobiol. 6, 342–349.10.1016/S0959-4388(96)80118-8Search in Google Scholar

McGehee, D.S., Heath, M.J., Gelber, S., Devay, P., and Role, L.W. (1995). Nicotine enhancement of fast excitatory synaptic transmission in CNS by presynaptic receptors. Science 269, 1692–1696.10.1126/science.7569895Search in Google Scholar PubMed

McKay, B.E., Placzek, A.N., and Dani, J.A. (2007). Regulation of synaptic transmission and plasticity by neuronal nicotinic acetylcholine receptors. Biochem. Pharmacol. 74, 1120–1133.10.1016/j.bcp.2007.07.001Search in Google Scholar PubMed PubMed Central

Mesulam, M.M. (1995). Cholinergic pathways and the ascending reticular activating system of the human brain. Ann. NY Acad. Sci. 757, 169–179.10.1111/j.1749-6632.1995.tb17472.xSearch in Google Scholar PubMed

Mineur, Y.S. and Picciotto, M.R. (2010). Nicotine receptors and depression: revisiting and revising the cholinergic hypothesis. Trends Pharmacol. Sci. 31, 580–586.10.1016/ in Google Scholar PubMed PubMed Central

Miwa, J.M., Freedman, R., and Lester, H.A. (2011). Neural systems governed by nicotinic acetylcholine receptors: emerging hypotheses. Neuron 70, 20–33.10.1016/j.neuron.2011.03.014Search in Google Scholar PubMed PubMed Central

Morris, G., Arkadir, D., Nevet, A., Vaadia, E., and Bergman, H. (2004). Coincident but distinct messages of midbrain dopamine and striatal tonically active neurons. Neuron 43, 133–143.10.1016/j.neuron.2004.06.012Search in Google Scholar PubMed

Nagel, G., Szellas, T., Huhn, W., Kateriya, S., Adeishvili, N., Berthold, P., Ollig, D., Hegemann, P., and Bamberg, E. (2003). Channelrhodopsin-2, a directly light-gated cation-selective membrane channel. Proc. Natl. Acad. Sci. USA 100, 13940–13945.10.1073/pnas.1936192100Search in Google Scholar PubMed PubMed Central

Nagode, D.A., Tang, A.H., Karson, M.A., Klugmann, M., and Alger, B.E. (2011). Optogenetic release of ACh induces rhythmic bursts of perisomatic IPSCs in hippocampus. PLoS One 6, e27691.10.1371/journal.pone.0027691Search in Google Scholar PubMed PubMed Central

Nagode, D.A., Tang, A.H., Yang, K., and Alger, B.E. (2014). Optogenetic identification of an intrinsic cholinergically driven inhibitory oscillator sensitive to cannabinoids and opioids in hippocampal CA1. J. Physiol. 592, 103–123.10.1113/jphysiol.2013.257428Search in Google Scholar PubMed PubMed Central

Nelson, A.B., Hammack, N., Yang, C.F., Shah, N.M., Seal, R.P., and Kreitzer, A.C. (2014). Striatal cholinergic interneurons drive GABA release from dopamine terminals. Neuron 82, 63–70.10.1016/j.neuron.2014.01.023Search in Google Scholar PubMed PubMed Central

Nickerson Poulin, A., Guerci, A., El Mestikawy, S., and Semba, K. (2006). Vesicular glutamate transporter 3 immunoreactivity is present in cholinergic basal forebrain neurons projecting to the basolateral amygdala in rat. J. Comp. Neurol. 498, 690–711.10.1002/cne.21081Search in Google Scholar

O’Malley, D.M., Sandell, J.H., and Masland, R.H. (1992). Co-release of acetylcholine and GABA by the starburst amacrine cells. J. Neurosci. 12, 1394–1408.10.1523/JNEUROSCI.12-04-01394.1992Search in Google Scholar

Paolone, G., Angelakos, C.C., Meyer, P.J., Robinson, T.E., and Sarter, M. (2013). Cholinergic control over attention in rats prone to attribute incentive salience to reward cues. J. Neurosci. 33, 8321–8335.10.1523/JNEUROSCI.0709-13.2013Search in Google Scholar

Parikh, V. and Sarter, M. (2008). Cholinergic mediation of attention: contributions of phasic and tonic increases in prefrontal cholinergic activity. Ann. NY Acad. Sci. 1129, 225–235.10.1196/annals.1417.021Search in Google Scholar

Picciotto, M.R., Caldarone, B.J., Brunzell, D.H., Zachariou, V., Stevens, T.R., and King, S.L. (2001). Neuronal nicotinic acetylcholine receptor subunit knockout mice: physiological and behavioral phenotypes and possible clinical implications. Pharmacol. Ther. 92, 89–108.10.1016/S0163-7258(01)00161-9Search in Google Scholar

Picciotto, M.R., Brunzell, D.H., and Caldarone, B.J. (2002). Effect of nicotine and nicotinic receptors on anxiety and depression. Neuroreport 13, 1097–1106.10.1097/00001756-200207020-00006Search in Google Scholar PubMed

Picciotto, M.R., Addy, N.A., Mineur, Y.S., and Brunzell, D.H. (2008). It is not “either/or”: activation and desensitization of nicotinic acetylcholine receptors both contribute to behaviors related to nicotine addiction and mood. Prog. Neurobiol. 84, 329–342.10.1016/j.pneurobio.2007.12.005Search in Google Scholar PubMed PubMed Central

Picciotto, M.R., Higley, M.J., and Mineur, Y.S. (2012). Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior. Neuron 76, 116–129.10.1016/j.neuron.2012.08.036Search in Google Scholar PubMed PubMed Central

Pinto, L., Goard, M.J., Estandian, D., Xu, M., Kwan, A.C., Lee, S.H., Harrison, T.C., Feng, G., and Dan, Y. (2013). Fast modulation of visual perception by basal forebrain cholinergic neurons. Nat. Neurosci. 16, 1857–1863.10.1038/nn.3552Search in Google Scholar PubMed PubMed Central

Platt, B. and Riedel, G. (2011). The cholinergic system, EEG and sleep. Behav. Brain Res. 221, 499–504.10.1016/j.bbr.2011.01.017Search in Google Scholar PubMed

Rawls, S.M., McGinty, J.F., and Terrian, D.M. (1999). Presynaptic kappa-opioid and muscarinic receptors inhibit the calcium-dependent component of evoked glutamate release from striatal synaptosomes. J. Neurochem. 73, 1058–1065.10.1046/j.1471-4159.1999.0731058.xSearch in Google Scholar

Ren, J., Qin, C., Hu, F., Tan, J., Qiu, L., Zhao, S., Feng, G., and Luo, M. (2011). Habenula “cholinergic” neurons co-release glutamate and acetylcholine and activate postsynaptic neurons via distinct transmission modes. Neuron 69, 445–452.10.1016/j.neuron.2010.12.038Search in Google Scholar

Richardson, P.J. and Brown, S.J. (1987). ATP release from affinity-purified rat cholinergic nerve terminals. J. Neurochem. 48, 622–630.10.1111/j.1471-4159.1987.tb04138.xSearch in Google Scholar

Sandberg, K., Sanberg, P.R., and Coyle, J.T. (1984). Effects of intrastriatal injections of the cholinergic neurotoxin AF64A on spontaneous nocturnal locomotor behavior in the rat. Brain Res. 299, 339–343.10.1016/0006-8993(84)90715-7Search in Google Scholar

Sarter, M., Parikh, V., and Howe, W.M. (2009). Phasic acetylcholine release and the volume transmission hypothesis: time to move on. Nat. Rev. Neurosci. 10, 383–390.10.1038/nrn2635Search in Google Scholar

Sarter, M., Lustig, C., Howe, W.M., Gritton, H., and Berry, A.S. (2014). Deterministic functions of cortical acetylcholine. Eur. J. Neurosci. 39, 1912–1920.10.1111/ejn.12515Search in Google Scholar

Schliebs, R., Rossner, S., and Bigl, V. (1996). Immunolesion by 192IgG-saporin of rat basal forebrain cholinergic system: a useful tool to produce cortical cholinergic dysfunction. Prog. Brain Res. 109, 253–264.10.1016/S0079-6123(08)62109-3Search in Google Scholar

Schoenenberger, P., Scharer, Y.P., and Oertner, T.G. (2011). Channelrhodopsin as a tool to investigate synaptic transmission and plasticity. Exp. Physiol. 96, 34–39.10.1113/expphysiol.2009.051219Search in Google Scholar PubMed

Schulz, J.M. and Reynolds, J.N. (2013). Pause and rebound: sensory control of cholinergic signaling in the striatum. Trends Neurosci. 36, 41–50.10.1016/j.tins.2012.09.006Search in Google Scholar PubMed

Schulz, J.M., Oswald, M.J., and Reynolds, J.N. (2011). Visual-induced excitation leads to firing pauses in striatal cholinergic interneurons. J. Neurosci. 31, 11133–11143.10.1523/JNEUROSCI.0661-11.2011Search in Google Scholar PubMed PubMed Central

Semenova, S., Contet, C., Roberts, A.J., and Markou, A. (2012). Mice lacking the beta4 subunit of the nicotinic acetylcholine receptor show memory deficits, altered anxiety- and depression-like behavior, and diminished nicotine-induced analgesia. Nicotine Tob. Res. 14, 1346–1355.10.1093/ntr/nts107Search in Google Scholar PubMed PubMed Central

Soll, L.G., Grady, S.R., Salminen, O., Marks, M.J., and Tapper, A.R. (2013). A role for a4(non-a6)* nicotinic acetylcholine receptors in motor behavior. Neuropharmacology 73C, 19–30.10.1016/j.neuropharm.2013.05.001Search in Google Scholar PubMed PubMed Central

Straub, C., Tritsch, N.X., Hagan, N.A., Gu, C., and Sabatini, B.L. (2014). Multiphasic modulation of cholinergic interneurons by nigrostriatal afferents. J. Neurosci. 34, 8557–8569.10.1523/JNEUROSCI.0589-14.2014Search in Google Scholar PubMed PubMed Central

Sugita, S., Uchimura, N., Jiang, Z.G., and North, R.A. (1991). Distinct muscarinic receptors inhibit release of gamma-aminobutyric acid and excitatory amino acids in mammalian brain. Proc. Natl. Acad. Sci. USA 88, 2608–2611.10.1073/pnas.88.6.2608Search in Google Scholar PubMed PubMed Central

Sumikawa, K., Houghton, M., Smith, J.C., Bell, L., Richards, B.M., and Barnard, E.A. (1982). The molecular cloning and characterisation of cDNA coding for the alpha subunit of the acetylcholine receptor. Nucleic Acids Res. 10, 5809–5822.10.1093/nar/10.19.5809Search in Google Scholar PubMed PubMed Central

Sun, Y.G., Pita-Almenar, J.D., Wu, C.S., Renger, J.J., Uebele, V.N., Lu, H.C., and Beierlein, M. (2013). Biphasic cholinergic synaptic transmission controls action potential activity in thalamic reticular nucleus neurons. J. Neurosci. 33, 2048–2059.10.1523/JNEUROSCI.3177-12.2013Search in Google Scholar PubMed PubMed Central

Surmeier, D.J. and Graybiel, A.M. (2012). A feud that wasn’t: acetylcholine evokes dopamine release in the striatum. Neuron 75, 1–3.10.1016/j.neuron.2012.06.028Search in Google Scholar PubMed PubMed Central

Taly, A., Corringer, P.J., Guedin, D., Lestage, P., and Changeux, J.P. (2009). Nicotinic receptors: allosteric transitions and therapeutic targets in the nervous system. Nat. Rev. Drug Discov. 8, 733–750.10.1038/nrd2927Search in Google Scholar PubMed

Threlfell, S. and Cragg, S.J. (2011). Dopamine signaling in dorsal versus ventral striatum: the dynamic role of cholinergic interneurons. Front. Syst. Neurosci. 5, 11.10.3389/fnsys.2011.00011Search in Google Scholar PubMed PubMed Central

Threlfell, S., Clements, M.A., Khodai, T., Pienaar, I.S., Exley, R., Wess, J., and Cragg, S.J. (2010). Striatal muscarinic receptors promote activity dependence of dopamine transmission via distinct receptor subtypes on cholinergic interneurons in ventral versus dorsal striatum. J. Neurosci. 30, 3398–3408.10.1523/JNEUROSCI.5620-09.2010Search in Google Scholar PubMed PubMed Central

Threlfell, S., Lalic, T., Platt, N.J., Jennings, K.A., Deisseroth, K., and Cragg, S.J. (2012). Striatal dopamine release is triggered by synchronized activity in cholinergic interneurons. Neuron 75, 58–64.10.1016/j.neuron.2012.04.038Search in Google Scholar

Tye, K.M. and Deisseroth, K. (2012). Optogenetic investigation of neural circuits underlying brain disease in animal models. Nat. Rev. Neurosci. 13, 251–266.10.1038/nrn3171Search in Google Scholar

Tye, K.M., Prakash, R., Kim, S.Y., Fenno, L.E., Grosenick, L., Zarabi, H., Thompson, K.R., Gradinaru, V., Ramakrishnan, C., and Deisseroth, K. (2011). Amygdala circuitry mediating reversible and bidirectional control of anxiety. Nature 471, 358–362.10.1038/nature09820Search in Google Scholar

Vanini, G., Lydic, R., and Baghdoyan, H.A. (2012). GABA-to-ACh ratio in basal forebrain and cerebral cortex varies significantly during sleep. Sleep 35, 1325–1334.10.5665/sleep.2106Search in Google Scholar

Vidal, C. and Changeux, J.P. (1993). Nicotinic and muscarinic modulations of excitatory synaptic transmission in the rat prefrontal cortex in vitro. Neuroscience 56, 23–32.10.1016/0306-4522(93)90558-WSearch in Google Scholar

von Engelhardt, J., Eliava, M., Meyer, A.H., Rozov, A., and Monyer, H. (2007). Functional characterization of intrinsic cholinergic interneurons in the cortex. J. Neurosci. 27, 5633–5642.10.1523/JNEUROSCI.4647-06.2007Search in Google Scholar

Wang, H., Peca, J., Matsuzaki, M., Matsuzaki, K., Noguchi, J., Qiu, L., Wang, D., Zhang, F., Boyden, E., Deisseroth, K., et al. (2007). High-speed mapping of synaptic connectivity using photostimulation in channelrhodopsin-2 transgenic mice. Proc. Natl. Acad. Sci. USA 104, 8143–8148.10.1073/pnas.0700384104Search in Google Scholar

Wenk, G.L. (1997). The nucleus basalis magnocellularis cholinergic system: one hundred years of progress. Neurobiol. Learn. Mem. 67, 85–95.10.1006/nlme.1996.3757Search in Google Scholar

Wess, J. (2003). Novel insights into muscarinic acetylcholine receptor function using gene targeting technology. Trends Pharmacol. Sci. 24, 414–420.10.1016/S0165-6147(03)00195-0Search in Google Scholar

Wiley, R.G. (1996). Targeting toxins to neural antigens and receptors. Semin. Cancer Biol. 7, 71–77.10.1006/scbi.1996.0011Search in Google Scholar PubMed

Witten, I.B., Lin, S.C., Brodsky, M., Prakash, R., Diester, I., Anikeeva, P., Gradinaru, V., Ramakrishnan, C., and Deisseroth, K. (2010). Cholinergic interneurons control local circuit activity and cocaine conditioning. Science 330, 1677–1681.10.1126/science.1193771Search in Google Scholar

Wonnacott, S. (1997). Presynaptic nicotinic ACh receptors. Trends Neurosci. 20, 92–98.10.1016/S0166-2236(96)10073-4Search in Google Scholar

Wonnacott, S., Barik, J., Dickinson, J., and Jones, I.W. (2006). Nicotinic receptors modulate transmitter cross talk in the CNS: nicotinic modulation of transmitters. J. Mol. Neurosci. 30, 137–140.10.1385/JMN:30:1:137Search in Google Scholar

Wrenn, C.C. and Wiley, R.G. (1998). The behavioral functions of the cholinergic basal forebrain: lessons from 192 IgG-saporin. Int. J. Dev. Neurosci. 16, 595–602.10.1016/S0736-5748(98)00071-9Search in Google Scholar

Yakel, J.L. (2010). Gating of nicotinic ACh receptors: latest insights into ligand binding and function. J. Physiol. 588, 597–602.10.1113/jphysiol.2009.182691Search in Google Scholar

Yakel, J.L. (2013). Cholinergic receptors: functional role of nicotinic ACh receptors in brain circuits and disease. Pflugers Arch. 465, 441–450.10.1007/s00424-012-1200-1Search in Google Scholar

Yang, K., Buhlman, L., Khan, G.M., Nichols, R.A., Jin, G., McIntosh, J.M., Whiteaker, P., Lukas, R.J., and Wu, J. (2011). Functional nicotinic acetylcholine receptors containing alpha6 subunits are on GABAergic neuronal boutons adherent to ventral tegmental area dopamine neurons. J. Neurosci. 31, 2537–2548.10.1523/JNEUROSCI.3003-10.2011Search in Google Scholar

Yizhar, O., Fenno, L.E., Davidson, T.J., Mogri, M., and Deisseroth, K. (2011). Optogenetics in neural systems. Neuron 71, 9–34.10.1016/j.neuron.2011.06.004Search in Google Scholar

Zaborszky, L. (2002). The modular organization of brain systems. Basal forebrain: the last frontier. Prog. Brain Res. 136, 359–372.10.1016/S0079-6123(02)36030-8Search in Google Scholar

Zhang, Y.P. and Oertner, T.G. (2007). Optical induction of synaptic plasticity using a light-sensitive channel. Nat. Methods 4, 139–141.10.1038/nmeth988Search in Google Scholar

Zhang, W., Basile, A.S., Gomeza, J., Volpicelli, L.A., Levey, A.I., and Wess, J. (2002). Characterization of central inhibitory muscarinic autoreceptors by the use of muscarinic acetylcholine receptor knock-out mice. J. Neurosci. 22, 1709–1717.10.1523/JNEUROSCI.22-05-01709.2002Search in Google Scholar

Zhang, F., Aravanis, A.M., Adamantidis, A., de Lecea, L., and Deisseroth, K. (2007a). Circuit-breakers: optical technologies for probing neural signals and systems. Nat. Rev. Neurosci. 8, 577–581.10.1038/nrn2192Search in Google Scholar PubMed

Zhang, F., Wang, L.P., Brauner, M., Liewald, J.F., Kay, K., Watzke, N., Wood, P.G., Bamberg, E., Nagel, G., Gottschalk, A., et al. (2007b). Multimodal fast optical interrogation of neural circuitry. Nature 446, 633–639.10.1038/nature05744Search in Google Scholar PubMed

Zhang, F., Gradinaru, V., Adamantidis, A.R., Durand, R., Airan, R.D., de Lecea, L., and Deisseroth, K. (2010). Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures. Nat. Prot. 5, 439–456.10.1038/nprot.2009.226Search in Google Scholar PubMed PubMed Central

Zhang, F., Vierock, J., Yizhar, O., Fenno, L.E., Tsunoda, S., Kianianmomeni, A., Prigge, M., Berndt, A., Cushman, J., Polle, J., et al. (2011). The microbial opsin family of optogenetic tools. Cell 147, 1446–1457.10.1016/j.cell.2011.12.004Search in Google Scholar PubMed PubMed Central

Zhou, F.M., Wilson, C.J., and Dani, J.A. (2002). Cholinergic interneuron characteristics and nicotinic properties in the striatum. J. Neurobiol. 53, 590–605.10.1002/neu.10150Search in Google Scholar PubMed

Zoli, M. and Picciotto, M.R. (2012). Nicotinic regulation of energy homeostasis. Nicotine Tob. Res. 14, 1270–1290.10.1093/ntr/nts159Search in Google Scholar PubMed PubMed Central

Zwart, R. and Vijverberg, H.P. (1997). Potentiation and inhibition of neuronal nicotinic receptors by atropine: competitive and noncompetitive effects. Mol. Pharmacol. 52, 886–895.10.1124/mol.52.5.886Search in Google Scholar PubMed

Received: 2014-5-2
Accepted: 2014-6-27
Published Online: 2014-7-22
Published in Print: 2014-12-1

©2014 by De Gruyter

Downloaded on 1.3.2024 from
Scroll to top button