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7 The CM/PF as a Target for Neurosurgical Interventions in Brain Disorders

7 The CM/PF as a Target for Neurosurgical Interventions in Brain Disorders

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4 The Thalamostriatal System and Cognition


of the CM/Pf-striatal system in attention, set-shifting, and cognitive flexibility is

highly significant because these functions are impaired in neurodegenerative diseases

that affect the basal ganglia, particularly PD and HD. The fact that CM/Pf neurons

undergo massive degeneration in these diseases further supports this possibility.

Future studies aimed at dissecting out the respective role of the CM-putamen versus

Pf-caudate nucleus in cognition, and the involvement of these networks in cognitive

impairments associated with PD are warranted. On a therapeutic perspective, additional knowledge about the cellular and molecular properties of CM/Pf neurons that

make them particularly sensitive to neurodegeneration must be gained, so that potential protective or neurorestorative therapies can be considered.

Acknowledgments This work was supported by grants from the National Institutes of Health to

YS and TW (R01 NS083386; P50NS071669) and the NIH infrastructure grant to the Yerkes

National Primate Research Center (P51 OD011132).


Ackermans L, Temel Y, Cath D et al (2006) Deep brain stimulation in Tourette’s syndrome: two

targets? Mov Disord 21:709–713

Ackermans L, Temel Y, Visser-Vandewalle V (2008) Deep brain stimulation in Tourette’s syndrome. Neurotherapeutics 5:339–344

Ackermans L, Duits A, Temel Y et al (2010) Long-term outcome of thalamic deep brain stimulation in two patients with Tourette syndrome. J Neurol Neurosurg Psychiatry 81:1068–1072

Ackermans L, Duits A, van der Linden C et al (2011) Double-blind clinical trial of thalamic stimulation in patients with Tourette syndrome. Brain 134:832–844

Alexander GE, DeLong MR, Strick PL (1986) Parallel organization of functionally segregated

circuits linking basal ganglia and cortex. Annu Rev Neurosci 9:357–381

Alexander GE, Crutcher MD, DeLong MR (1990) Basal ganglia-thalamocortical circuits: parallel

substrates for motor, oculomotor, “prefrontal” and “limbic” functions. Prog Brain Res


Alloway KD, Smith JB, Watson GDR (2014) Thalamostriatal projections from the medial posterior and parafascicular nuclei have distinct topographic and physiologic properties.

J Neurophysiol 111:36–50

Bajwa RJ, de Lotbiniere AJ, King RA et al (2007) Deep brain stimulation in Tourette’s syndrome.

Mov Disord 22:1346–1350

Balleine BW, O’Doherty JP (2010) Human and rodent homologies in action control: corticostriatal

determinants of goal-directed and habitual action. Neuropsychopharmacology 35:48–69

Balleine BW, Liljeholm M, Ostlund SB (2009) The integrative function of the basal ganglia in

instrumental conditioning. Behav Brain Res 199:43–52

Barroso-Chinea P, Rico AJ, Conte-Perales L et al (2011) Glutamatergic and cholinergic pedunculopontine neurons innervate the thalamic parafascicular nucleus in rats: changes following

experimental parkinsonism. Brain Struct Funct. doi:10.1007/s00429-011-0317-x

Beckstead RM (1984) The thalamostriatal projection in the cat. J Comp Neurol 223:313–346

Berendse HW, Groenewegen HJ (1990) Organization of the thalamostriatal projections in the rat,

with special emphasis on the ventral striatum. J Comp Neurol 299:187–228

Bradfield LA, Hart G, Balleine BW (2013a) The role of the anterior, mediodorsal, and parafascicular thalamus in instrumental conditioning. Front Syst Neurosci 7:51

Bradfield LA, Bertran-Gonzalez J, Chieng B et al (2013b) The thalamostriatal pathway and cholinergic control of goal-directed action: interlacing new with existing learning in the striatum.

Neuron 79:153–166


Y. Smith et al.

Brooks D, Halliday GM (2009) Intralaminar nuclei of the thalamus in Lewy body diseases. Brain

Res Bull 78:97–104

Brown RG, Marsden CD (1990) Cognitive function in Parkinson’s disease: from description to

theory. Trends Neurosci 13:21–29

Brown HD, Baker PM, Ragozzino ME (2010) The parafascicular thalamic nucleus concomitantly

influences behavioral flexibility and dorsomedial striatal acetylcholine output in rats. J Neurosci


Butler AB (1994) The evolution of the dorsal pallium in the telencephalon of amniotes: cladistic

analysis and a new hypothesis. Brain Res Brain Res Rev 19:66–101

Caparros-Lefebvre D, Blond S, Feltin MP et al (1999) Improvement of levodopa induced dyskinesias by thalamic deep brain stimulation is related to slight variation in electrode placement:

possible involvement of the centre median and parafascicularis complex. J Neurol Neurosurg

Psychiatry 67:308–314

Chevalier G, Deniau JM (1984) Spatio-temporal organization of a branched tecto-spinal/tectodiencephalic neuronal system. Neuroscience 12:427–439

Comans PE, Snow PJ (1981) Ascending projections to nucleus parafascicularis of the cat. Brain

Res 230:337–341

Cornwall J, Phillipson OT (1988) Afferent projections to the parafascicular thalamic nucleus of the

rat, as shown by the retrograde transport of wheat germ agglutinin. Brain Res Bull 20:139–150

Cowan WM, Powell TP (1956) A study of thalamo-striate relations in the monkey. Brain


de Divitiis E, D’Errico A, Cerillo A (1977) Stereotactic surgery in Gilles de la Tourette syndrome.

Acta Neurochir (Wien) 24:73

de las Heras S, Mengual E, Velayos JL et al (1998) Re-examination of topographic distribution of

thalamic neurons projecting to the caudate nucleus. A retrograde labeling study in the cat.

Neurosci Res 31:283–293

de las Heras S, Mengual E, Gimenez-Amaya JM (1999) Double retrograde tracer study of the

thalamostriatal projections to the cat caudate nucleus. Synapse 32:80–92

Deng YP, Wong T, Wan JY et al (2014) Differential loss of thalamostriatal and corticostriatal input

to striatal projection neuron types prior to overt motor symptoms in the Q140 knock-in mouse

model of Huntington’s disease. Front Syst Neurosci 8:198

Deschenes M, Bourassa J, Parent A (1995) Two different types of thalamic fibers innervate the rat

striatum. Brain Res 701:288–292

Dimberger G, Jahanshahi M (2013) Executive dysfunction in Parkinson’s disease: a review.

J Neuropsychol 7:193–224

Ding JB, Guzman JN, Peterson JD et al (2010) Thalamic gating of corticostriatal signaling by

cholinergic interneurons. Neuron 67:294–307

Edwards SB, de Olmos JS (1976) Autoradiographic studies of the projections of the midbrain

reticular formation: ascending projections of nucleus cuneiformis. J Comp Neurol


Ellender TJ, Harwood J, Kosillo P et al (2013) Heterogeneous properties of central lateral and

parafascicular thalamic synapses in the striatum. J Physiol 591:257–272

Erro EM, Lanciego JL, Gimenez-Amaya JM (2002) Re-examination of the thalamostriatal projections in the rat with retrograde tracers. Neurosci Res 42:45–55

Fisher SD, Reynolds JN (2014) The intralaminar thalamus-an expressway linking visual stimuli to

circuits determining agency and action selection. Front Behav Neurosci 8:115

Galvan A, Smith Y (2011) The primate thalamostriatal systems: anatomical organization, functional roles and possible involvement in Parkinson’s disease. Basal Ganglia 1:179–189

Galvan A, Villalba RM, Wichmann T, Smith Y (2016) The thalamostriatal systems in normal and

diseased states. In: Steiner HZ, Tseng K-Y (eds) Handbook of basal ganglia structure and function, 2nd edn. Elsevier, Amsterdam

Gerrits NJ, Van der Werf YD, Verhoef KM et al (2015) Compensatory fronto-parietal hyperactivation during set-shifting in unmedicate patients with Parkinson’s disease. Neuropsychologia


4 The Thalamostriatal System and Cognition


Gimenez-Amaya JM, McFarland NR, de las Heras S et al (1995) Organization of thalamic projections to the ventral striatum in the primate. J Comp Neurol 354:127–149

Goldberg JA, Reynolds JN (2011) Spontaneous firing and evoked pauses in the tonically active

cholinergic interneurons of the striatum. Neuroscience 198:27–43

Grahn JA, Parkinson JA, Owen AM (2008) The cognitive functions of the caudate nucleus. Prog

Neurobiol 86:141–155

Grahn JA, Parkinson JA, Owen AM (2009) The role of the basal ganglia in learning and memory:

neuropsychological studies. Behav Brain Res 199:53–60

Groenewegen HJ, Berendse HW (1994) The specificity of the ‘nonspecific’ midline and intralaminar thalamic nuclei. Trends Neurosci 17:52–57

Grunwerg BS, Krauthamer GM (1992) Sensory responses of intralaminar thalamic neurons activated by the superior colliculus. Exp Brain Res 88:541–550

Haber SN, Brucker JL (2009) Cognitive and limbic circuits that are affected by deep brain stimulation. Front Biosci 14:1823–1834

Haber S, McFarland NR (2001) The place of the thalamus in frontal cortical-basal ganglia circuits.

Neuroscientist 7:315–324

Hallanger AE, Levey AI, Lee HJ et al (1987) The origins of cholinergic and other subcortical

afferents to the thalamus in the rat. J Comp Neurol 262:105–124

Halliday GM (2009) Thalamic changes in Parkinson’s disease. Parkinsonism Relat Disord


Hariz MI, Robertson MM (2010) Gilles de la Tourette syndrome and deep brain stimulation. Eur J

Neurosci 32:1128–1134

Hassler R (1982) Stereotaxic surgery for psychiatric disturbances. In: Schaltenbrand G, Walker AE

(eds) Stereotaxy of the human brain. Thieme-Stratton, New York, pp 570–590

Hassler R, Dieckmann G (1970) Stereotaxic treatment of tics and inarticulate cries or coprolalia

considered as motor obsessional phenomena in Gilles de la Tourette’s disease. Rev Neurol

(Paris) 123:89–100

Hassler R, Dieckmann G (1973) Relief of obsessive-compulsive disorders, phobias and tics by

stereotactic coagulations of the rostral intralaminar and medial-thalamic nuclei. In: Laitinen

LV, Livingston K (eds) Proceedings of the third international congress of psychosurgery.

Garden City Press, Cambridge, pp 206–212

Heinsen H, Rub U, Gangnus D et al (1996) Nerve cell loss in the thalamic centromedianparafascicular complex in patients with Huntington’s disease. Acta Neuropathol 91:161–168

Henderson JM, Carpenter K, Cartwright H et al (2000a) Loss of thalamic intralaminar nuclei in

progressive supranuclear palsy and Parkinson’s disease: clinical and therapeutic implications.

Brain 123:1410–1421

Henderson JM, Carpenter K, Cartwright H et al (2000b) Degeneration of the centre medianparafascicular complex in Parkinson’s disease. Ann Neurol 47:345–352

Henderson JM, Schleimer SB, Allbutt H et al (2005) Behavioural effects of parafascicular thalamic lesions in an animal model of parkinsonism. Behav Brain Res 162:222–232

Herkenham M, Pert CB (1981) Mosaic distribution of opiate receptors, parafascicular projections

and acetylcholinesterase in rat striatum. Nature 291:415–418

Houeto JL, Karachi C, Mallet L et al (2005) Tourette’s syndrome and deep brain stimulation.

J Neurol Neurosurg Psychiatry 76:992–995

Howe MW, Atallah HE, McCool A et al (2011) Habit learning is associated with major shifts in

frequencies of oscillatory activity and synchronized spike firing in striatum. Proc Natl Acad Sci

U S A 108:16801–16806

Ichinohe N, Shoumura K (1998) A di-synaptic projection from the superior colliculus to the head

of the caudate nucleus via the centromedian-parafascicular complex in the cat: an anterograde

and retrograde labeling study. Neurosci Res 32:295–303

Ichinohe N, Iwatsuki H, Shoumura K (2001) Intrastriatal targets of projection fibers from the central lateral nucleus of the rat thalamus. Neurosci Lett 302:105–108


Y. Smith et al.

Iwai H, Kuramoto E, Yamanaka A et al (2015) Ascending parabrachio-thalamo-striatal pathways:

potential circuits for integration of gustatory and oral functions. Neuroscience 294:1–13

Jog MS, Kubota Y, Connolly CI et al (1999) Building neural representations of habits. Science


Kato S, Kuramochi M, Kobayashi K et al (2011) Selective neural pathway targeting reveals key

roles of thalamostriatal projection in the control of visual discrimination. J Neurosci


Kim JP, Min HK, Knight EJ et al (2013) Centromedian-parafascicular deep brain stimulation

induces differential functional inhibition of the motor, associative, and limbic circuits in large

animals. Biol Psychiatry 74:917–926

Kimura M, Minamimoto T, Matsumoto N et al (2004) Monitoring and switching of cortico-basal

ganglia loop functions by the thalamo-striatal system. Neurosci Res 48:355–360

Kinomura S, Larsson J, Gulyas B et al (1996) Activation by attention of the human reticular formation and thalamic intralaminar nuclei. Science 271:512–515

Krack P, Hariz MI, Baunez C et al (2010) Deep brain stimulation: from neurology to psychiatry?

Trends Neurosci 33:474–484

Krout KE, Loewy AD, Westby GW et al (2001) Superior colliculus projections to midline and

intralaminar thalamic nuclei of the rat. J Comp Neurol 431:198–216

Lavoie B, Parent A (1991) Serotoninergic innervation of the thalamus in the primate: an immunohistochemical study. J Comp Neurol 312:1–18

Liebermann D, Ostendorf F, Kopp UA et al (2013) Subjective cognitive-affective status following

thalamic stroke. J Neurol 260:386–396

Maciunas RJ, Maddux BN, Riley DE et al (2007) Prospective randomized double-blind trial of

bilateral thalamic deep brain stimulation in adults with Tourette syndrome. J Neurosurg


Maling N, Hashemiyoon R, Foote KD et al (2012) Increased thalamic gamma band activity correlates with symptom relief following deep brain stimulation in humans with Tourette’s syndrome. PLoS One 7, e44215

Matsumoto N, Minamimoto T, Graybiel AM et al (2001) Neurons in the thalamic CM-Pf complex

supply striatal neurons with information about behaviorally significant sensory events.

J Neurophysiol 85:960–976

Mazzone P, Stocchi F, Galati S et al (2006) Bilateral implantation of centromedian-parafascicularis

complex and GPi: a new combination of unconventional targets for deep brain stimulation in

severe Parkinson disease. Neuromodulation 9:221–228

McFarland NR, Haber SN (2001) Organization of thalamostriatal terminals from the ventral motor

nuclei in the macaque. J Comp Neurol 429:321–336

Mengual E, de las Heras S, Erro E et al (1999) Thalamic interaction between the input and the

output systems of the basal ganglia. J Chem Neuroanat 16:187–200

Mennemeier M, Crosson B, Williamson DJ et al (1997) Tapping, talking and the thalamus: possible influence of the intralaminar nuclei on basal ganglia function. Neuropsychologia


Minamimoto T, Kimura M (2002) Participation of the thalamic CM-Pf complex in attentional

orienting. J Neurophysiol 87:3090–3101

Minamimoto T, Hori Y, Kimura M (2005) Complementary process to response bias in the centromedian nucleus of the thalamus. Science 308:1798–1801

Minamimoto T, Hori Y, Kimura M (2009) Roles of the thalamic CM-PF complex-basal ganglia

circuit in externally driven rebias of action. Brain Res Bull 78:75–79

Minamimoto T, Hori Y, Yamanaka K et al (2014) Neural signal for counteracting pre-action bias in

the centromedian thalamic nucleus. Front Syst Neurosci 8:3

Mink JW (2006) Neurobiology of basal ganglia and Tourette syndrome: basal ganglia circuits and

thalamocortical outputs. Adv Neurol 99:89–98

Moss J, Bolam JP (2008) A dopaminergic axon lattice in the striatum and its relationship with

cortical and thalamic terminals. J Neurosci 28:11221–11230

4 The Thalamostriatal System and Cognition


Nakano K, Hasegawa Y, Tokushige A et al (1990) Topographical projections from the thalamus,

subthalamic nucleus and pedunculopontine tegmental nucleus to the striatum in the Japanese

monkey, Macaca fuscata. Brain Res 537:54–68

Nanda B, Galvan A, Smith Y et al (2009) Effects of stimulation of the centromedian nucleus of the

thalamus on the activity of striatal cells in awake rhesus monkeys. Eur J Neurosci 29:588–598

Neuner I, Podoll K, Janouschek H et al (2009) From psychosurgery to neuromodulation: deep

brain stimulation for intractable Tourette syndrome. World J Biol Psychiatry 10:366–376

Newman DB, Ginsberg CY (1994) Brainstem reticular nuclei that project to the thalamus in rats:

a retrograde tracer study. Brain Behav Evol 44:1–39

O’Callaghan C, Bertoux M, Hornberger M (2014) Beyond and below the cortex: the contribution

of striatal dysfunction to cognition and behaviour in neurodegeneration. J Neurol Neurosurg

Psychiatry 85:371–378

Pare D, Smith Y, Parent A et al (1988) Projections of brainstem core cholinergic and non-cholinergic

neurons of cat to intralaminar and reticular thalamic nuclei. Neuroscience 25:69–86

Parent M, Parent A (2005) Single-axon tracing and three-dimensional reconstruction of centre

median-parafascicular thalamic neurons in primates. J Comp Neurol 481:127–144

Parent A, Mackey A, De Bellefeuille L (1983) The subcortical afferents to caudate nucleus and putamen in primate: a fluorescence retrograde double labeling study. Neuroscience 10:1137–1150

Parent A, Pare D, Smith Y et al (1988) Basal forebrain cholinergic and noncholinergic projections

to the thalamus and brainstem in cats and monkeys. J Comp Neurol 277:281–301

Peppe A, Gasbarra A, Stefani A et al (2008) Deep brain stimulation of CM/PF of thalamus could

be the new elective target for tremor in advanced Parkinson’s disease? Parkinsonism Relat

Disord 14:501–504

Porta M, Brambilla A, Cavanna AE et al (2009) Thalamic deep brain stimulation for treatmentrefractory Tourette syndrome: two-year outcome. Neurology 73:1375–1380

Powell TP, Cowan WM (1954) The connexions of the midline and intralaminar nuclei of the thalamus of the rat. J Anat 88:307–319

Powell TPS, Cowan WM (1956) A study of thalamo-striate relations in the monkey. Brain


Ragsdale CW Jr, Graybiel AM (1991) Compartmental organization of the thalamostriatal connection in the cat. J Comp Neurol 311:134–167

Raju DV, Shah DJ, Wright TM et al (2006) Differential synaptology of vGluT2-containing thalamostriatal afferents between the patch and matrix compartments in rats. J Comp Neurol


Raju DV, Ahern TH, Shah DJ et al (2008) Differential synaptic plasticity of the corticostriatal and

thalamostriatal systems in an MPTP-treated monkey model of parkinsonism. Eur J Neurosci


Redgrave P, Rodriguez M, Smith Y et al (2010) Goal-directed and habitual control in the basal

ganglia: implications for Parkinson’s disease. Nat Rev Neurosci 11:760–772

Reiner A, Hart NM, Lei W, Deng Y (2010) Corticostriatal projection neurons—dichotomous types

and dichotomous functions. Front Neuroanat 4:142

Rice ME (2000) Distinct regional differences in dopamine-mediated volume transmission. Prog

Brain Res 125:277–290

Robbins TW, Cools R (2014) Cognitive deficits in Parkinson’s disease: a cognitive neuroscience

perspective. Mov Disord 29:597–607

Royce GJ, Bromley S, Gracco C (1991) Subcortical projections to the centromedian and parafascicular thalamic nuclei in the cat. J Comp Neurol 306:129–155

Sassi M, Porta M, Servello D (2011) Deep brain stimulation therapy for treatment-refractory

Tourette’s syndrome: a review. Acta Neurochir(Wien) 153:639–645

Savica R, Stead M, Mack KJ et al (2012) Deep brain stimulation in tourette syndrome: a description of 3 patients with excellent outcome. Mayo Clin Proc 87:59–62

Schiff ND (2008) Central thalamic contributions to arousal regulation and neurological disorders

of consciousness. Ann N Y Acad Sci 1129:105–118


Y. Smith et al.

Schiff ND (2009) Central thalamic deep-brain stimulation in the severely injured brain: rationale

and proposed mechanisms of action. Ann N Y Acad Sci 1157:101–116

Schiff ND (2013) Central thalamic deep brain stimulation for support of forebrain arousal regulation in the minimally conscious state. Handb Clin Neurol 116:295–306

Schiff ND, Giacino JT, Kalmar K et al (2007) Behavioural improvements with thalamic stimulation after severe traumatic brain injury. Nature 448:600–603

Servello D, Porta M, Sassi M et al (2008) Deep brain stimulation in 18 patients with severe Gilles

de la Tourette syndrome refractory to treatment: the surgery and stimulation. J Neurol

Neurosurg Psychiatry 79:136–142

Servello D, Sassi M, Brambilla A et al (2010) Long-term, post-deep brain stimulation management

of a series of 36 patients affected with refractory gilles de la tourette syndrome. Neuromodulation


Shields DC, Cheng ML, Flaherty AW et al (2008) Microelectrode-guided deep brain stimulation

for Tourette syndrome: within-subject comparison of different stimulation sites. Stereotact

Funct Neurosurg 86:87–91

Sidibe M, Smith Y (1996) Differential synaptic innervation of striatofugal neurones projecting to

the internal or external segments of the globus pallidus by thalamic afferents in the squirrel

monkey. J Comp Neurol 365:445–465

Sidibe M, Smith Y (1999) Thalamic inputs to striatal interneurons in monkeys: synaptic organization and co-localization of calcium binding proteins. Neuroscience 89:1189–1208

Sidibe M, Bevan MD, Bolam JP et al (1997) Efferent connections of the internal globus pallidus

in the squirrel monkey: I. Topography and synaptic organization of the pallidothalamic projection. J Comp Neurol 382:323–347

Sidibe M, Pare JF, Smith Y (2002) Nigral and pallidal inputs to functionally segregated thalamostriatal neurons in the centromedian/parafascicular intralaminar nuclear complex in monkey. J Comp Neurol 447:286–299

Smith Y, Parent A (1986) Differential connections of caudate nucleus and putamen in the squirrel

monkey (Saimiri sciureus). Neuroscience 18:347–371

Smith Y, Bennett BD, Bolam JP et al (1994) Synaptic relationships between dopaminergic afferents and cortical or thalamic input in the sensorimotor territory of the striatum in monkey.

J Comp Neurol 344:1–19

Smith Y, Raju DV, Pare JF et al (2004) The thalamostriatal system: a highly specific network of the

basal ganglia circuitry. Trends Neurosci 27:520–527

Smith Y, Raju D, Nanda B et al (2009) The thalamostriatal systems: anatomical and functional

organization in normal and parkinsonian states. Brain Res Bull 78:60–68

Smith Y, Surmeier DJ, Redgrave P et al (2011) Thalamic contributions to basal ganglia-related

behavioral switching and reinforcement. J Neurosci 31:16102–16106

Smith Y, Galvan A, Ellender TJ et al (2014) The thalamostriatal system in normal and diseased

states. Front Syst Neurosci 8:5

Stefani A, Peppe A, Pierantozzi M et al (2009) Multi-target strategy for Parkinsonian patients: the

role of deep brain stimulation in the centromedian-parafascicularis complex. Brain Res Bull


Stephenson-Jones M, Samuelsson E, Ericsson J et al (2011) Evolutionary conservation of the basal

ganglia as a common vertebrate mechanism for action selection. Curr Biol 21:1081–1091

Steriade M, Glenn LL (1982) Neocortical and caudate projections of intralaminar thalamic neurons and their synaptic excitation from midbrain reticular core. J Neurophysiol 48:352–371

Tanaka D Jr, Isaacson LG, Trosko BK (1986) Thalamostriatal projections from the ventral anterior

nucleus in the dog. J Comp Neurol 247:56–68

Temel Y, Visser-Vandewalle V (2004) Surgery in Tourette syndrome. Mov Disord 19:3–14

Van der Werf YD, Witter MP, Groenewegen HJ (2002) The intralaminar and midline nuclei of the

thalamus. Anatomical and functional evidence for participation in processes of arousal and

awareness. Brain Res Brain Res Rev 39:107–140

4 The Thalamostriatal System and Cognition


Vertes RP, Martin GF (1988) Autoradiographic analysis of ascending projections from the pontine

and mesencephalic reticular formation and the median raphe nucleus in the rat. J Comp Neurol


Vertes RP, Linley SB, Hoover WB (2010) Pattern of distribution of serotonergic fibers to the thalamus of the rat. Brain Struct Funct 215:1–28

Villalba RM, Wichmann T, Smith Y (2014) Neuronal loss in the caudal intralaminar thalamic

nuclei in a primate model of Parkinson’s disease. Brain Struct Funct 219:381–394

Villalba RM, Mathai A, Smith Y (2015) Morphological changes of glutamatergic synapses in animal models of Parkinson’s disease. Front Neuroanat 9:117

Visser-Vandewalle V, Kuhn J (2013) Deep brain stimulation for Tourette syndrome. Handb Clin

Neurol 116:251–258

Visser-Vandewalle V, Temel Y, Boon P et al (2003) Chronic bilateral thalamic stimulation: a new

therapeutic approach in intractable Tourette syndrome. Report of three cases. J Neurosurg


Visser-Vandewalle V, Temel Y, van der Linden C et al (2004) Deep brain stimulation in movement

disorders. The applications reconsidered. Acta Neurol Belg 104:33–36

Visser-Vandewalle V, Ackermans L, van der Linden C et al (2006) Deep brain stimulation in Gilles

de la Tourette’s syndrome. Neurosurgery 58, E590

Vogt C, Vogt O (1941a) Thalamusstudien I-III: I. Zur Einführung. II. Homogenität and

Grenzgestaltung der Grisea des Thalamus. III. Das Griseum centrale (Centrum medianum

Luys). J Psychol Neurol 50:32–154

Vogt C, Vogt O (1941b) Thalamusstudien I-III. I. Zur Einfurung, II. Homogenitat und

Grenzgestaldung der Grisea des Thalamus, III. Griseum centrale (centrum medianum Luys).

J Physiol Neurol 50:31–154

Wall NR, De La Parra M, Callaway EM et al (2013) Differential innervation of direct- and indirectpathway striatal projection neurons. Neuron 79:347–360

Xuereb JH, Perry RH, Candy JM et al (1991) Nerve cell loss in the thalamus in Alzheimer’s disease and Parkinson’s disease. Brain 114(pt 3):1363–1379

Yin HH, Knowlton BJ (2006) The role of the basal ganglia in habit formation. Nat Rev Neurosci


Chapter 5

Dopamine and Its Actions in the Basal Ganglia


Daniel Bullock


Introduction: Consensus Summary of Dopamine’s

Actions in the Circuitry of the Basal Ganglia

There have been many recent excellent reviews of selected aspects of the dopamine

(DA) system, including the range of stimuli and internal signals to which DA neurons respond (e.g., Bromberg-Martin et al. 2010; Schultz 2013), how DA release

depends jointly on DA neuron firing and myriad factors present at release sites in

the basal ganglia (BG) (e.g., Rice et al. 2011), the systematic effects of DA in the

striatum (e.g., Gerfen and Surmeier 2011), and the role dopamine plays in various

neurological disorders (e.g., Linnet 2014; Lloyd et al. 2014; Covey et al. 2014;

Belujon and Grace 2015; Nutt et al. 2015) beyond its critical role in Parkinson’s

disease and schizophrenia (e.g., Iversen and Iversen 2007). This chapter will reprise

many of the key findings needed to understand the consensus that is emerging about

the neural systems—especially the BG system—within which DA plays its most

critical role.

Like noradrenaline (NA), dopamine (DA) is an aminergic neurotransmitter, and

Dahlström and Fuxe (1964) identified and designated 14 clusters of aminergic neurons: A1–A7 designate NA clusters, and A8–A14 designate DA clusters, most in the

midbrain (see also Björklund and Dunnett 2007). In each cluster, DA cells are mixed

with other cell types, but in all of these clusters, the aminergic neurons represent a

large proportion of cells, and they typically project aminergic axons far beyond the

nuclei in which their somas reside. Other brain structures also contain intermixed

D. Bullock, Ph.D. (*)

Department of Psychological and Brain Sciences, Boston University,

677 Beacon Street, Boston, MA 02215, USA

e-mail: danb@bu.edu

© Springer International Publishing Switzerland 2016

J.-J. Soghomonian (ed.), The Basal Ganglia, Innovations in Cognitive

Neuroscience, DOI 10.1007/978-3-319-42743-0_5



D. Bullock

DA neurons—a good example is the retina—but these neurons are not a large proportion of the total, and function as interneurons, with no projections beyond the

area. Recently, Fuxe and colleagues (2010) reviewed the huge literature that has

developed since the A8–A14 clusters were mapped. They reprised impressive evidence that (1) a highly similar mapping applies across a wide range of mammalian

species and (2) DA often works via volume transmission, which utilizes diffusion

well beyond release sites (Rice and Cragg 2008; but see Ishikawa et al. 2013), hence

does not require that the DA release sites be immediately adjacent to the receptors

at which DA acts. Of course, all systemically delivered neuroactive drugs also work

via volume transmission, after crossing the blood–brain barrier. Consistent with this

mode of operation, single DA neurons exhibit remarkably widespread branching,

with multiple axonal bushes, in target areas such as the striatum (e.g., Matsuda et al

2009). Thus, DA is typically regarded as a nonspecific, “broadcast” signal, highly

distinct from the specific, topographically organized projections found in other neural systems, e.g., at successive stages of processing within a sensory modality, or in

the motor output pathways.

Although DA signals play diverse roles in the neural symphony, one prototypical

and vital role is as a primary mediator of the ancient learning process by which

animals explore novel environments and thereby learn both to choose actions that

are expected to lead to more rewarding outcomes, and to suppress actions expected

to lead to less rewarding or aversive outcomes. Dopamine strongly affects such

learning via its systematic effects on LTD and LTP of glutamatergic synapses

between afferents to striatum and the medium spiny neurons (MSPNs) that project

from striatum to other BG nuclei. However, DA also has strong effects on performance, including both motor and cognitive performance. Its influence on performance is powerfully attested by the tight link between striatal DA loss and

Parkinsonian akinesia, but it is also revealed in much subtler ways, such as a higher

velocity of eye movements to rewarded than to equidistant but non-rewarded targets

(Hong and Hikosaka 2011), and altered reaction time distributions following sleep

deprivation, which have been reproduced in a computational model that includes

dopamine–adenosine interactions in striatum (Bullock and St. Hilaire 2014).

Action selection based on expected outcomes is enabled by mammalian forebrain circuits, among which the striatum and other constituents of the BG (see

Fig. 5.1) have a preeminent status (Swanson 2005; Gurney et al. 2015). Although

DA innervation is densest in striatum, it also reaches many other parts of the brain,

especially parts of the BG, thalamus, and cerebral cortex. Moreover, the innervation

of cerebral cortex is significantly more elaborated in primates than in rodents (Smith

et al. 2014). Because operation of the BG is so critically dependent on dense innervation from DA neurons of cluster A10 (much of which falls in the VTA), A9

(mostly in the SNc), and A8 (mostly in the retrorubral area = RRA), these pools are

regarded as an integral part of the BG system in this chapter. Thus, the BG system

spans cells found in both the subcortical forebrain and the midbrain.

DA acts differentially in striatum by facilitating a “direct”, action-promoting

pathway, and by simultaneously dis-facilitating an “indirect”, action-opposing path-

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