Skip to main content
Book cover

Optogenetics pp 265–277Cite as

Optogenetic Analysis of Striatal Connections to Determine Functional Connectomes

  • Chapter

Abstract

Neural circuit function is determined not only by anatomical connections but also by the strength and nature of the connections, that is functional connectivity. To elucidate functional connectivity, selective stimulation of presynaptic terminals of an identified neuronal population is crucial. However in the central nervous system (CNS), intermingled input fibers make selective electrical stimulation impossible. With optogenetics this becomes possible, and enables the comprehensive study of functional synaptic connections between an identified population of neurons and defined postsynaptic targets to determine the functional connectome. By stimulating convergent synaptic inputs impinging on individual postsynaptic neurons, low frequency and small amplitude synaptic connections can be detected. Further, the optogenetic approach enables measurement of cotransmission and its relative strength. In this chapter, optogenetic studies in the striatum (Str) are introduced to demonstrate the functional connectome approach. For spiny projection neurons, this has revealed cell-type specific intra-striatal connections as well as striatal output connections. Cholinergic interneurons in the ventral striatum have been shown to use glutamate as a cotransmitter. Examining striatal afferents from the ventral midbrain has identified fast, direct dopaminergic connection onto cholinergic interneurons and preferential connections of γ-aminobutyric acid (GABA) neurons to cholinergic interneurons in the nucleus accumbens. Further, it has revealed regionally heterogeneous glutamate and GABA cotransmission of dopamine neurons in the Str. These connections can be quite plastic, revealing a new vista of connectivity that is likely to be important in understanding the circuitry of neuropsychiatric disorders.

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

Buying options

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

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Al-Juboori SI, Dondzillo A, Stubblefield EA et al (2013) Light scattering properties vary across different regions of the adult mouse brain. PLoS One 8(7):e67626. doi:10.1371/journal.pne.0067626

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Beckstead MJ, Grandy DK, Wickman K et al (2004) Vesicular dopamine release elicits an inhibitory postsynaptic current in midbrain dopamine neurons. Neuron 42(6):939–946

    Article  CAS  PubMed  Google Scholar 

  • Belujon P, Grace AA (2011) Hippocampus, amygdala, and stress: Interacting systems that affect susceptibility to addiction. Annal NY Acad Sci 1216:114–121

    Article  CAS  Google Scholar 

  • Bertran-Gonzalez J, Bosch C, Maroteaux M et al (2008) Opposing patterns of signaling activation in dopamine D1 and D2 receptor-expressing striatal neurons in response to cocaine and haloperidol. J Neurosci 28(22):5671–5685

    Article  CAS  PubMed  Google Scholar 

  • Bocklisch C, Pascoli V, Wong JCY et al (2013) Cocaine disinhibits dopamine neurons by potentiation of GABA transmission in the ventral tegmental area. Science 341(6153):1521–1525

    Article  CAS  PubMed  Google Scholar 

  • Brown MTC, Tan KR, O’Connor EC et al (2013) Ventral tegmental area GABA projections pause accumbal cholinergic interneurons to enhance associative learning. Nature 492(7429):452–456

    Article  Google Scholar 

  • Cazorla M, de Carvalho FD, Chohan MO et al (2014) Dopamine D2 receptors regulate the anatomical and functional balance of basal ganglia circuitry. Neuron 81(1):153–164

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chuhma N, Zhang H, Masson J et al (2004) Dopamine neurons mediate a fast excitatory signal via their glutamatergic synapses. J Neurosci 24(4):972–981

    Article  CAS  PubMed  Google Scholar 

  • Chuhma N, Tanaka KF, Hen R et al (2011) Functional connectome of the striatal medium spiny neuron. J Neurosci 31(4):1183–1192

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chuhma N, Mingote S, Moore H et al (2014) Dopamine neurons control striatal cholinergic neurons via regionally heterogeneous dopamine and glutamate signaling. Neuron 81(4):901–912

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cooper AJ, Stanford IM (2000) Electrophysiological and morphological characteristics of three subtypes of rat globus pallidus neurone in vitro. J Physiol 527(2):291–304

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dautan D, Huerta-Ocampo I, Witten IB et al (2014) A major external source of cholinergic innervation of the striatum and nucleus accumbens originates in the brainstem. J Neurosci 34(13):4509–4518

    Article  PubMed Central  PubMed  Google Scholar 

  • Ding JB, Oh W-J, Sabatini BL et al (2012) Semaphorin 3E-plexin-D1 signaling controls pathway-specific synapse formation in the striatum. Nature Neurosci 15(2):215–223

    Article  CAS  Google Scholar 

  • Ellender TJ, Harwood J, Kosillo P et al (2013) Heterogeneous properties of central lateral and parafascicular thalamic synapses in the striatum. J Physiol 591(1):257–272

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Exley R, Cragg SJ (2008) Presynaptic nicotinic receptors: A dynamic and diverse cholinergic filter of striatal dopamine neurotransmission. Brit J Pharmacol 153(Suppl 1):S283–S297

    CAS  Google Scholar 

  • Feinberg EH, Vanhoven MK, Bendesky A et al (2008) GFP reconstitution across synaptic partners (GRASP) defines cell contacts and synapses in living nervous systems. Neuron 57(3):353–363

    Article  CAS  PubMed  Google Scholar 

  • Fremeau RT, Burman J, Qureshi T et al (2002) The identification of vesicular glutamate transporter 3 suggests novel modes of signaling by glutamate. Proc Nat Acad Sci 99(22):14488–14493

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Friston KJ, Frith CD, Liddle PF et al (1993) Functional connectivity: The principal-component analysis of large (PET) data sets. J Cereb Blood Flow Metab 13(1):5–14

    Article  CAS  PubMed  Google Scholar 

  • Fujiyama F, Sohn J, Nakano T et al (2011) Exclusive and common targets of neostriatofugal projections of rat striosome neurons: A single neuron-tracing study using a viral vector. Eur J Neurosci 33(4):668–677

    Article  PubMed  Google Scholar 

  • Gangarossa G, Espallergues J, de Kerchove d’Exaerde A et al. (2013) Distribution and compartmental organization of gabaergic medium-sized spiny neurons in the mouse nucleus accumbens. Front Neural Circuits 7:22. doi: 10.3389/fncir.2013.00022

  • Gantz SC, Bunzow JR, Williams JT (2013) Spontaneous inhibitory synaptic currents mediated by a g protein-coupled receptor. Neuron 78(5):807–812

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gerfen CR (1985) The neostriatal mosaic. I Compartmental organization of projections from the striatum to the substantia nigra in the rat. J Comp Neurol 236(4):454–476

    Article  CAS  PubMed  Google Scholar 

  • Gerfen CR, Surmeier DJ (2011) Modulation of striatal projection systems by dopamine. Ann Rev Neurosci 34:441–466

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Graybiel AM (2008) Habits, rituals, and the evaluative brain. Ann Rev Neurosci 31:359–387

    Article  CAS  PubMed  Google Scholar 

  • Haber SN, Fudge JL, McFarland NR (2000) Striatonigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum. J Neurosci 20(6):2369–2382

    CAS  PubMed  Google Scholar 

  • Higley MJ, Gittis AH, Oldenburg IA et al (2011) Cholinergic interneurons mediate fast VGLUT3-dependent glutamatergic transmission in the striatum. PLoS One 6(4):e19155. doi:10.1371/journal.pone.0019155

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ikemoto S (2007) Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens-olfactory tubercle complex. Brain Res Rev 56(1):27–78

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Jackman SL, Beneduce BM, Drew IR et al (2014) Achieving high-frequency optical control of synaptic transmission. J Neurosci 34(22):7704–7714

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kita H (2007) Globus pallidus external segment. Prog Brain Res 160:111–133

    CAS  PubMed  Google Scholar 

  • Kreitzer AC (2009) Physiology and pharmacology of striatal neurons. Ann Rev Neurosci 32:127–147

    Article  CAS  PubMed  Google Scholar 

  • Lichtman JW, Sanes JR (2008) Ome sweet ome: What can the genome tell us about the connectome? Curr Opin Neurobiol 18(3):346–353

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lin JY, Knutsen PM, Muller A et al (2013) ReaChR: a red-shifted variant of channelrhodopsin enables deep transcranial optogenetic excitation. Nat Neurosci 16(10):1499–1508

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mastro KJ, Bouchard RS, Holt HAK et al (2014) Transgenic mouse lines subdivide external segment of the globus pallidus (GPe) neurons and reveal distinct gpe output pathways. J Neurosci 34(6):2087–2099

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mayford M, Bach ME, Huang YY et al (1996) Control of memory formation through regulated expression of a CaMKII transgene. Science 274(5293):1678–1683

    Article  CAS  PubMed  Google Scholar 

  • Mingote S, Chuhma N, Kusnoor SV et al (2012) The VTA dopamine neuron excitatory functional connectome. In: Champalimaud Neuroscience Symposium 2012, Champalimaud Centre for the Unknown, Lisbon, 30 Sep–3 Oct 2012

    Google Scholar 

  • Oldenburg IA, Ding JB (2011) Cholinergic modulation of synaptic integration and dendritic excitability in the striatum. Curr Opin Neurobiol 21(3):425–432

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pennartz CMA, Berke JD, Graybiel AM et al (2009) Corticostriatal interactions during learning, memory processing, and decision making. J Neurosci 29(41):12831–12838

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Seung HS (2009) Reading the book of memory: Sparse sampling versus dense mapping of connectomes. Neuron 62(1):17–29

    Article  CAS  PubMed  Google Scholar 

  • Shepherd GM (1994) Neurobiology, 3rd edn. Oxford University Press, Oxford

    Google Scholar 

  • Sporns O, Tononi G, Kötter R (2005) The human connectome: a structural description of the human brain. Plos Comput Biol 1(4):e42. doi:10.1371/journal.pcbi.0010042

    Article  PubMed Central  PubMed  Google Scholar 

  • Stuber GD, Hnasko TS, Britt JP et al (2010) Dopaminergic terminals in the nucleus accumbens but not the dorsal striatum corelease glutamate. J Neurosci 30(24):8229–8233

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Stuber GD, Sparta DR, Stamatakis AM et al (2011) Excitatory transmission from the amygdala to nucleus accumbens facilitates reward seeking. Nature 475(7356):377–380

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sulzer D, Joyce MP, Lin L et al (1998) Dopamine neurons make glutamatergic synapses in vitro. J Neurosci 18(12):4588–4602

    CAS  PubMed  Google Scholar 

  • Szydlowski SN, Pollak Dorocic I, Planert H et al (2013) Target selectivity of feedforward inhibition by striatal fast-spiking interneurons. J Neurosci 33(4):1678–1683

    Article  CAS  PubMed  Google Scholar 

  • Taverna S, Ilijic E, Surmeier DJ (2008) Recurrent collateral connections of striatal medium spiny neurons are disrupted in models of Parkinson’s disease. J Neurosci 28(21):5504–5512

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tecuapetla F, Patel JC, Xenias H et al (2010) Glutamatergic signaling by mesolimbic dopamine neurons in the nucleus accumbens. J Neurosci 30(20):7105–7110

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tepper JM, Koós T, Wilson CJ (2004) Gabaergic microcircuits in the neostriatum. Trend Neurosci 27(11):662–669

    Article  CAS  PubMed  Google Scholar 

  • Tepper JM, Tecuapetla F, Koos T et al (2010) Heterogeneity and diversity of striatal gabaergic interneurons. Front Neuroanat 4:150. doi:10.3389/fnana.2010.00150

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tritsch NX, Ding JB, Sabatini BL (2012) Dopaminergic neurons inhibit striatal output through non-canonical release of GABA. Nature 490(7419):262–266

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tritsch NX, Oh WJ, Gu C et al (2014) Midbrain dopamine neurons sustain inhibitory transmission using plasma membrane uptake of GABA, not synthesis. eLife 3:e01936. doi:10.7554/eLife.01936

  • Van Bockstaele EJ, Pickel VM (1995) GABA-containing neurons in the ventral tegmental area project to the nucleus accumbens in rat brain. Brain Res 682(1–2):215–221

    Article  PubMed  Google Scholar 

  • Watabe-Uchida M, Zhu L, Ogawa SK et al (2012) Whole-brain mapping of direct inputs to midbrain dopamine neurons. Neuron 74(5):858–873

    Article  CAS  PubMed  Google Scholar 

  • Wilson CJ (2004) The basal ganglia. In: Shepherd GM (ed) The synaptic organization of the brain, 5th edn. Oxford University Press, Oxford, pp 361–413

    Chapter  Google Scholar 

  • Xia Y, Driscoll JR, Wilbrecht L et al (2011) Nucleus accumbens medium spiny neurons target non-dopaminergic neurons in the ventral tegmental area. J Neurosci 31(21):7811–7816

    Article  CAS  PubMed  Google Scholar 

  • Yamaguchi T, Sheen W, Morales M (2007) Glutamatergic neurons are present in the rat ventral tegmental area. Eur J Neurosci 25(1):106–118

    Article  PubMed Central  PubMed  Google Scholar 

  • Yin HH, Knowlton BJ (2006) The role of the basal ganglia in habit formation. Nat Rev Neurosci 7(6):464–476

    Article  CAS  PubMed  Google Scholar 

  • Yizhar O, Fenno LE, Davidson TJ et al (2011) Optogenetics in neural systems. Neuron 71(1):9–34

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nao Chuhma .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Japan

About this chapter

Cite this chapter

Chuhma, N. (2015). Optogenetic Analysis of Striatal Connections to Determine Functional Connectomes. In: Yawo, H., Kandori, H., Koizumi, A. (eds) Optogenetics. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55516-2_18

Download citation

Publish with us

Policies and ethics