Dopamine gating of glutamatergic sensorimotor and incentive motivational input signals to the striatum

doi:10.1016/S0166-4328(02)00285-1

Behavioural Brain Research

Volume 137, Issues 1–2, 2 December 2002, Pages 65-74

https://doi.org/10.1016/S0166-4328(02)00285-1 Get rights and content

Abstract

Dopamine (DA) neurons of the substantia nigra (SN) and ventral tegmental area (VTA) respond to a wide category of salient stimuli. Activation of SN and VTA DA neurons, and consequent release of nigrostriatal and mesolimbic DA, modulates the processing of concurrent glutamate inputs to dorsal and ventral striatal target regions. According to the view described here, this occurs under conditions of unexpected environmental change regardless of whether that change is rewarding or aversive. Nigrostriatal and mesolimbic DA activity gates the input of sensory, motor, and incentive motivational (e.g. reward) signals to the striatum. In light of recent single-unit and brain imaging data, it is suggested that the striatal reward signals originate in the orbitofrontal cortex and basolateral amygdala (BLA), regions that project strongly to the striatum. A DA signal of salient unexpected event occurrence, from this framework, gates the throughput of the orbitofrontal glutamate reward input to the striatum just as it gates the throughput of corticostriatal sensory and motor signals needed for normal response execution. Processing of these incoming signals is enhanced when synaptic DA levels are high, because DA enhances the synaptic efficacy of strong concurrent glutamate inputs while reducing the efficacy of weak glutamate inputs. The impairments in motor performance and incentive motivational processes that follow from nigrostriatal and mesolimbic DA loss can be understood in terms of a single mechanism: abnormal processing of sensorimotor and incentive motivation-related glutamate input signals to the striatum.

Section snippets

Overview

Dopamine (DA) neurons of the substantia nigra (SN) and ventral tegmental area (VTA) respond to unexpected reward events [102]. However these cells respond to a wide category of salient stimuli [57], [99]-unexpected rewards are one member of this category. While it has been suggested that reward stimuli may be unique in producing a phasic DA response and that other arousing stimuli may produce only gradual DA elevations [102], this assumption is not made here. Novel, intense, rewarding,

DA neurons respond to salient unexpected events

Among the attributes that may imbue an event with salience are 1) novelty, 2) primary and conditioned reward properties, 3) primary and conditioned aversive properties, and 4) physical characteristics such as high intensity and fast rise-time. VTA DA neurons, i.e. those that give rise to mesolimbocortical DA pathways, respond to each of these types of salient events [57]. Single-unit recordings have demonstrated that VTA DA neurons show phasic elevations in activity in response to novel events

DA selectively promotes the processing of strong glutamate inputs to the striatum

If DA is a gatekeeper for glutamate input to the striatum, it is a selective gatekeeper that, within dorsal and ventral striatal regions, enhances the impact of strong input signals while dampening the impact of weaker signals [26], [27], [67], [88]. Cells in the dorsal and ventral striatum undergo transitions from a state of hyperpolarization (ca. −80 mV), far below the cell's action potential threshold, to a less polarized state (ca. −60 mV), within close range of action potential threshold

DA activity gates the throughput of sensorimotor and incentive motivational inputs to the striatum

The dorsal striatum receives glutamate inputs [42], [77] from virtually all sensory and motor regions of the cerebral cortex [64], [68], [71], [78], [107]. Neurons in the dorsolateral striatum (putamen) fire in relation to the movement of particular body parts [5], [23], [30], [31], [81], [121], and in some cases particular joints [2], [5], [31]. Some putamen cells show activity during the preparation of a movement [2], [53]. In some of these neurons, the neuronal activity during movement

Striatal plasticity: stimulus-response learning, salience assignment to synaptic inputs, and/or stimulus-response-outcome chunking

The prior discussion suggested that DA neurons are activated by salient environmental change and that elevations in synaptic DA activity within the striatum increase signal-to-noise ratios, permitting strong corticostriatal inputs privileged access to striatal outputs, by amplifying strong inputs and dampening the impact of weak (task-irrelevant) inputs. Further, it was noted that glutamate inputs to the striatum represent not only sensory and motor events, but also events coded on the basis of

Acknowledgements

I gratefully acknowledge Wayne Wicklegren, Marcel Kinsbourne, Jennifer Mangels, Peter Balsam, Yaniv Eyny, Amy Hale, Won Yung Choi, Michael Drew and Johannes Schwaninger with whom I have had stimulating discussions of these issues.

References (129)

G.E. Alexander et al.
Functional architecture of basal ganglia circuits: neural substrates of parallel processing
Trends Neurosci.
(1990)
R.J. Beninger
The role of dopamine in locomotor activity and learning
Brain Res.
(1983)
R.J. Beninger et al.
Microinjections of flupenthixol into the caudate-putamen but not the nucleus accumbens, amygdala or frontal cortex of rats produces intra- session declines in food-rewarded operant responding
Behav. Brain Res.
(1993)
K.C. Berridge
Food reward: brain substrates of wanting and liking
Neurosci. Biobehav. Rev.
(1996)
J.J. Bouyer et al.
Chemical and structural analysis of the relation between cortical inputs and tyrosine hydroxylase-containing terminals in rat neostriatum
Brain Res.
(1984)
L.H. Brauer et al.
High dose pimozide does not block amphetamine-induced euphoria in normal volunteers
Pharmacol. Biochem. Behav.
(1997)
L.H. Burns et al.
Differential effects of excitotoxic lesions of the basolateral amygdala, ventral subiculum and medial prefrontal cortex on responding with conditioned reinforcement and locomotor activity potentiated by intra-accumbens infusions of d-amphetamine
Behav. Brain Res.
(1993)
M. Cador et al.
Involvement of the amygdala in stimulus-reward associations: interaction with the ventral striatum
Neuroscience
(1989)
A. Chausmer et al.
Intraaccumbens raclopride attenuates amphetamine-induced locomotion, but fails to prevent the response-reinstating properties of food reinforcement
Pharmacol. Biochem. Behav.
(1999)
A.L. Chausmer et al.
A role for D2, but not D1, dopamine receptors in the response-reinstating effects of food reinforcement
Pharmacol. Biochem. Behav.
(1997)

J. Cho et al.

Distributions of single neurons related to body parts in the lateral striatum of the rat

Brain Res.

(1997)

C.L. Duvauchelle et al.

Haloperidol attenuates conditioned place preferences produced by electrical stimulation of the medial prefrontal cortex

Pharmacol. Biochem. Behav.

(1991)

C.L. Duvauchelle et al.

Opposite effects of prefrontal cortex and nucleus accumbens infusions of flupenthixol on stimulant-induced locomotion and brain stimulation reward

Brain Res.

(1992)

A. Ettenberg et al.

Pimozide prevents the response-reinstating effects of water reinforcement in rats

Pharmacol. Biochem. Behav.

(1990)

B.J. Everitt

Sexual motivation: a neural and behavioral analysis of the mechanisms underlying appetitive and copulatory responses of male rats

Neurosci. BioBehav. Rev.

(1990)

W.J. Freed

Glutamatergic mechanisms mediating stimulant and antipsychotic drug effects

Neurosci. Biobehav. Rev.

(1994)

A.M. Graybiel

The basal ganglia and chunking of action repertoires

Neurobiol. Learn Mem.

(1998)

F.A. Guarraci et al.

An electrophysiological characterization of ventral tegmental area dopaminergic neurons during differential pavlovian fear conditioning in the awake rabbit

Behav. Brain Res.

(1999)

J.L. Haracz et al.

Striatal single-unit responses to amphetamine and neuroleptics in freely moving rats

Neurosci. Biobehav. Rev.

(1993)

L. Heimer et al.

Substantia innominata: a notion, which impedes clinical–anatomical correlations in neuropsychiatric disorders

Neuroscience

(1997)

L. Hernandez et al.

Food reward and cocaine increase extracellular dopamine in the nucleus accumbens as measured by microdialysis

Life Sci.

(1988)

J.C. Horvitz

Mesolimbocortical and nigrostriatal dopamine responses to salient non-reward events

Neuroscience

(2000)

J.C. Horvitz et al.

Haloperidol blocks the response-reinstating effects of food reward: a methodology for separating neuroleptic effects on reinforcement and motor processes

Pharmacol. Biochem. Behav.

(1988)

J.C. Horvitz et al.

Burst activity of ventral tegmental dopamine neurons is elicited by sensory stimuli in the awake cat

Brain Res.

(1997)

S. Ikemoto et al.

The role of nucleus accumbens dopamine in motivated behavior: a unifying interpretation with special reference to reward seeking

Brain Res. Brain Res. Rev.

(1999)

B. Jones et al.

Limbic lesions and the problem of stimulus-reinforcement associations

Exp. Neurol.

(1972)

A.E. Kelley et al.

The amygdalostriatal projection in the rat-an anatomical study by anterograde and retrograde tracing methods

Neuroscience

(1982)

H. Kunzle

Bilateral projections from precentral motor cortex to the putamen and other parts of the basal ganglia. An autoradiographic study in Macaca fascicularis

Brain Res.

(1975)

S.L. Liles

Cortico–striatal evoked potentials in the monkey (Macaca mulatta)

Electroencephalogr. Clin. Neurophysiol.

(1975)

G.P. Mark et al.

An appetitively conditioned taste elicits a preferential increase in mesolimbic dopamine release

Pharmacol. Biochem. Behav.

(1994)

P.L. McGeer et al.

A glutamatergic corticostriatal path

Brain Res.

(1977)

A.J. McGeorge et al.

The organization of the projection from the cerebral cortex to the striatum in the rat

Neuroscience

(1989)

A.K. Moschovakis et al.

The microscopic anatomy and physiology of the mammalian saccadic system

Prog. Neurobiol.

(1996)

P. O'Donnell et al.

Dopaminergic reduction of excitability in nucleus accumbens neurons recorded in vitro

Neuropsychopharmacology

(1996)

S. Pecina et al.

Pimozide does not shift palatability: separation of anhedonia from sensorimotor suppression by taste reactivity

Pharmacol. Biochem. Behav.

(1997)

C.M. Pennartz et al.

The nucleus accumbens as a complex of functionally distinct neuronal ensembles: an integration of behavioral, electrophysiological and anatomical data

Prog. Neurobiol.

(1994)

C.M. Pennartz et al.

The glutamate hypothesis of reinforcement learning

Prog. Brain Res.

(2000)

P. Redgrave et al.

Is the short-latency dopamine response too short to signal reward error

Trends Neurosci.

(1999)

T.W. Robbins et al.

Limbic–striatal interactions in reward-related processes

Neurosci. Biobehav. Rev.

(1989)

J.D. Salamone

The involvement of nucleus accumbens dopamine in appetitive and aversive motivation

Behav. Brain Res.

(1994)

J.D. Salamone et al.

Behavioral functions of nucleus accumbens dopamine: empirical and conceptual problems with the anhedonia hypothesis

Neurosci. Biobehav. Rev.

(1997)

E. Acquas et al.

SCH 23390 blocks drug-conditioned place-preference and place-aversion: anhedonia (lack of reward) or apathy (lack of motivation) after dopamine-receptor blockade

Psychopharmacology

(1989)

G.E. Alexander

Selective neuronal discharge in monkey putamen reflects intended direction of planned limb movements

Exp. Brain Res.

(1987)

G.E. Alexander et al.

Neural representations of the target (goal) of visually guided arm movements in three motor areas of the monkey

J. Neurophysiol.

(1990)

G.E. Alexander et al.

Microstimulation of the primate neostriatum. II. Somatotopic organization of striatal microexcitable zones and their relation to neuronal response properties

J. Neurophysiol.

(1985)

T. Aosaki et al.

Effect of the nigrostriatal dopamine system on acquired neural responses in the striatum of behaving monkeys

Science

(1994)

P. Apicella et al.

Responses to reward in monkey dorsal and ventral striatum

Exp. Brain Res.

(1991)

A. Bechara et al.

Dissociation of working memory from decision making within the human prefrontal cortex

J. Neurosci.

(1998)

R.J. Beninger et al.

The effect of pimozide on the establishment of conditioned reinforcement

Psychopharmacology (Berlin)

(1980)

M. Bertolucci-D'Angio et al.

Differential effects of forced locomotion, tail-pinch, immobilization, and methyl-beta-carboline carboxylate on extracellular 3,4-dihydroxyphenylacetic acid levels in the rat striatum, nucleus accumbens, and prefrontal cortex: an in vivo voltammetric study

J. Neurochem.

(1990)

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Research reportDopamine gating of glutamatergic sensorimotor and incentive motivational input signals to the striatum

Abstract

Section snippets

Overview

DA neurons respond to salient unexpected events

DA selectively promotes the processing of strong glutamate inputs to the striatum

DA activity gates the throughput of sensorimotor and incentive motivational inputs to the striatum

Striatal plasticity: stimulus-response learning, salience assignment to synaptic inputs, and/or stimulus-response-outcome chunking

Acknowledgements

Trends Neurosci.

Brain Res.

Behav. Brain Res.

Neurosci. Biobehav. Rev.

Brain Res.

Pharmacol. Biochem. Behav.

Behav. Brain Res.

Neuroscience

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

Brain Res.

Pharmacol. Biochem. Behav.

Brain Res.

Pharmacol. Biochem. Behav.

Neurosci. BioBehav. Rev.

Neurosci. Biobehav. Rev.

Neurobiol. Learn Mem.

Behav. Brain Res.

Neurosci. Biobehav. Rev.

Neuroscience

Life Sci.

Neuroscience

Pharmacol. Biochem. Behav.

Brain Res.

Brain Res. Brain Res. Rev.

Exp. Neurol.

Neuroscience

Brain Res.

Electroencephalogr. Clin. Neurophysiol.

Pharmacol. Biochem. Behav.

Brain Res.

Neuroscience

Prog. Neurobiol.

Neuropsychopharmacology

Pharmacol. Biochem. Behav.

Prog. Neurobiol.

Prog. Brain Res.

Trends Neurosci.

Neurosci. Biobehav. Rev.

Behav. Brain Res.

Neurosci. Biobehav. Rev.

SCH 23390 blocks drug-conditioned place-preference and place-aversion: anhedonia (lack of reward) or apathy (lack of motivation) after dopamine-receptor blockade

Psychopharmacology

Selective neuronal discharge in monkey putamen reflects intended direction of planned limb movements

Exp. Brain Res.

Neural representations of the target (goal) of visually guided arm movements in three motor areas of the monkey

J. Neurophysiol.

Microstimulation of the primate neostriatum. II. Somatotopic organization of striatal microexcitable zones and their relation to neuronal response properties

J. Neurophysiol.

Effect of the nigrostriatal dopamine system on acquired neural responses in the striatum of behaving monkeys

Science

Responses to reward in monkey dorsal and ventral striatum

Exp. Brain Res.

Dissociation of working memory from decision making within the human prefrontal cortex

J. Neurosci.

The effect of pimozide on the establishment of conditioned reinforcement

Psychopharmacology (Berlin)

Differential effects of forced locomotion, tail-pinch, immobilization, and methyl-beta-carboline carboxylate on extracellular 3,4-dihydroxyphenylacetic acid levels in the rat striatum, nucleus accumbens, and prefrontal cortex: an in vivo voltammetric study

J. Neurochem.

Research report
Dopamine gating of glutamatergic sensorimotor and incentive motivational input signals to the striatum