A glutamatergic corticostriatal path?

McGeer, Patrick L.; McGeer, Edith G.; Scherer, Ulrike; Singh, Kartar

doi:10.1016/0006-8993(77)91003-4

Cited by 485 publications

(122 citation statements)

References 16 publications

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“…An increase in striatal dopamine signaling is regulated by actions on presynaptic and postsynaptic receptors and high-affinity dopamine transporters, while somatodendritic autoreceptors slow the firing rate of dopaminergic neurons and activation of nerve terminal autoreceptors inhibit the synthesis and release of dopamine (Dreyer and Hounsgaard, 2012;Meltzer, 1980). The firing of midbrain neurons is also mediated by presynaptic D2 receptors on the corticostriatal glutamate-containing projections from the prefrontal cortex to the ventral striatum (McGeer et al, 1977), and prefrontal dopaminergic activity also contributes to striatal dopamine release through descending midbrain and corticostriatal projections to attenuate phasic dopamine release in the ventral striatum (Grace, 1991).…”

Section: Discussionmentioning

confidence: 99%

Functional Genetic Variation in Dopamine Signaling Moderates Prefrontal Cortical Activity During Risky Decision Making

Kohno

Nurmi

Laughlin

et al. 2015

Neuropsychopharmacol

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Brain imaging has revealed links between prefrontal activity during risky decision-making and striatal dopamine receptors. Specifically, striatal dopamine D2-like receptor availability is correlated with risk-taking behavior and sensitivity of prefrontal activation to risk in the Balloon Analogue Risk Task (BART). The extent to which these associations, involving a single neurochemical measure, reflect more general effects of dopaminergic functioning on risky decision making, however, is unknown. Here, 65 healthy participants provided genotypes and performed the BART during functional magnetic resonance imaging. For each participant, dopamine function was assessed using a gene composite score combining known functional variation across five genes involved in dopaminergic signaling: DRD2, DRD3, DRD4, DAT1, and COMT. The gene composite score was negatively related to dorsolateral prefrontal cortical function during risky decision making, and nonlinearly related to earnings on the task. Iterative permutations of all possible allelic variations (7777 allelic combinations) was tested on brain function in an independently defined region of the prefrontal cortex and confirmed empirical validity of the composite score, which yielded stronger association than 95% of all other possible combinations. The gene composite score also accounted for a greater proportion of variability in neural and behavioral measures than the independent effects of each gene variant, indicating that the combined effects of functional dopamine pathway genes can provide a robust assessment, presumably reflecting the cumulative and potentially interactive effects on brain function. Our findings support the view that the links between dopaminergic signaling, prefrontal function, and decision making vary as a function of dopamine signaling capacity.

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Section: Discussionmentioning

confidence: 99%

Functional Genetic Variation in Dopamine Signaling Moderates Prefrontal Cortical Activity During Risky Decision Making

Kohno

Nurmi

Laughlin

et al. 2015

Neuropsychopharmacol

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“…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].…”

Section: Da Activity Gates the Throughput Of Sensorimotor And Incentimentioning

confidence: 99%

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

Horvitz

2002

Behavioural Brain Research

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“…T he striatum receives glutamatergic projections from virtually all areas of the cerebral cortex and dense dopaminergic projections from the substantia nigra and ventral tegmental area (1,2). The principal neurons of the striatum, medium spiny neurons (MSNs), are GABAergic projection neurons.…”

mentioning

confidence: 99%

Functional disturbances in the striatum by region-specific ablation of NMDA receptors

Ohtsuka

Tansky

Kuang

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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To study the role of NMDA receptors in dopamine signaling of the striatum, the brain area that receives glutamatergic inputs from various cortical areas and most dopaminergic inputs, we generated striatum-specific NMDA receptor-deficient mice. The mutant pups showed reduced food intake and retarded growth starting at the second postnatal week and died on approximately postnatal day 20 (P20). The time course of postnatal lethality is similar to that of compound mutant, double knockout of dopamine D1/D2 receptors, or genetically engineered dopamine-deficient mouse. In vivo electrophysiological recordings in the mutant pups showed that frequencies in the range of gamma oscillation were reduced in the striatal circuits. Moreover, the number of functional dopamine receptors in the striatum as measured by D1-and D2-binding experiments was greatly diminished in the mutants as compared with control animals. A consequence of diminished dopamine binding in the striatum manifested in an increase of locomotor activity. The administration of D1/D2 agonists paradoxically reduced the hyperactivity of the mutant mice as compared with an increase in locomotor activity in control mice. These results demonstrate that the NMDA receptor plays an essential role in the integration of dopamine signaling in the striatum and that is required in behavioral function.T he striatum receives glutamatergic projections from virtually all areas of the cerebral cortex and dense dopaminergic projections from the substantia nigra and ventral tegmental area (1, 2). The principal neurons of the striatum, medium spiny neurons (MSNs), are GABAergic projection neurons. These neurons are classified into two groups: the MSNs that express D1 dopamine receptors responsible for a direct pathway and the MSNs that express D2 dopamine receptors responsible for an indirect pathway (3). These MSNs constitute 90-95% of the striatal neuronal population (4) and contain high levels of NMDA receptors (5, 6).During development, dopamine receptor expressions (both D1 and D2) are already abundant by the late embryonic stage, however functional dopamine receptor binding is low at birth and progressively increases to reach adult levels between postnatal day (P)14 and P21 (7). This delayed appearance of functional dopamine receptors in the MSNs of the striatum suggests that maturation of functional dopamine receptors is regulated by an unknown mechanism, other than the mere availability of the dopamine receptor mRNAs.During postnatal weeks, it has been shown that the NMDA receptor-mediated currents develop later in the MSNs compared with other brain regions such as the hippocampus. There is a Ϸ2-fold increase from the first to the third postnatal week (8). Recently, molecular interactions between NMDA receptors and dopamine receptors have been reported. For example, NMDA receptors trap diffusible D1 receptors by direct physical interaction (9-11). The interaction between NR2B, a subunit of the NMDA receptor, and the D2 receptor can also disrupt the association of Ca 2ϩ /cal...

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A glutamatergic corticostriatal path?

Cited by 485 publications

References 16 publications

Functional Genetic Variation in Dopamine Signaling Moderates Prefrontal Cortical Activity During Risky Decision Making

Functional Genetic Variation in Dopamine Signaling Moderates Prefrontal Cortical Activity During Risky Decision Making

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

Functional disturbances in the striatum by region-specific ablation of NMDA receptors

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