The Primate Thalamus Is a Key Target for Brain Dopamine

Sánchez-González, Miguel Ángel; García‐Cabezas, Miguel Ángel; Rico, Beatriz; Cavada, Carmen

doi:10.1523/jneurosci.0968-05.2005

Cited by 258 publications

(207 citation statements)

References 48 publications

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“…These observations, when put in the context of the extra GABAergic and dopaminergic modulatory inputs noted in the introduction (Barthó et al, 2002;Bokor et al, 2005;Sanchez-Gonzalez et al, 2005), suggest that higher order nuclei may have modulatory effects not observed in first order nuclei. This, in turn, suggest that modulation of corticocortical processing through thalamus (i.e.…”

Section: Discussionmentioning

confidence: 83%

“…There are several subcortical, presumably modulatory, sources that tend to innervate higher order rather than first order nuclei. These include GABAergic inputs from the anterior pretectal nucleus and zona incerta (Barthó et al, 2002;Bokor et al, 2005) and dopaminergic inputs from an as yet undefined source (Sanchez-Gonzalez et al, 2005). There is also evidence for a difference in the postsynaptic effects of cholinergic inputs to thalamic relay cells (Mooney et al, 2004;Varela and Sherman, 2004): in first order nuclei, these are depolarizing, but in higher order nuclei, these are hyperpolarizing for a substantial minority of relay cells.…”

Section: Other Differences Between First Order and Higher Order Thalamentioning

confidence: 99%

“…GABAergic inputs from the zona incerta and pretectum plus dopaminergic inputs from an unspecified source selectively target higher order nuclei (Cucchiaro et al, 1991(Cucchiaro et al, , 1993Wang et al, 2002b;Bokor et al, 2005;Sanchez-Gonzalez et al, 2005). Also, cholinergic inputs from the parabrachial region hyperpolarize many higher order relay cells, whereas these inputs appear to depolarize all first order relay cells (Mooney et al, 2004;Varela and Sherman, 2004).…”

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Fewer driver synapses in higher order than in first order thalamic relays

Horn

Sherman

2007

Neuroscience

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Abstract-We used electron microscopy to determine the relative numbers of the three synaptic terminal types, RL (round vesicle, large terminal), RS (round vesicles, small terminal), and F (flattened vesicles), found in several representative thalamic nuclei in cats chosen as representative examples of first and higher order thalamic nuclei, where the first order nuclei relay subcortical information mainly to primary sensory cortex, and the higher order nuclei largely relay information from one cortical area to another. The nuclei sampled were the first order ventral posterior nucleus (somatosensory) and the ventral portion of the medial geniculate nucleus (auditory), and the higher order posterior nucleus (somatosensory) and the medial portion of the medial geniculate nucleus (auditory). We found that the relative percentage of synapses from RL terminals varied significantly among these nuclei, these values being higher for first order nuclei (12.6% for the ventral posterior nucleus and 8.2% for the ventral portion of the medial geniculate nucleus) than for the higher order nuclei (5.4% for the posterior nucleus, and 3.5% for the medial portion of the medial geniculate nucleus). This is consistent with a similar analysis of first and higher order nuclei for the visual system (the lateral geniculate nucleus and pulvinar, respectively). Since synapses from RL terminals represent the main information to be relayed, whereas synapses from F and RS terminals are modulatory in function, we conclude that there is relatively more modulation of the thalamic relay in the cortico-thalamo-cortical higher order pathway than in first order relays. © 2007 IBRO. Published by Elsevier Ltd. All rights reserved.Key words: ventral posterior nucleus, posterior nucleus, medial geniculate nucleus, neuromodulators, corticocortical communication. Sherman and Guillery (1998, 2006) first made the point that inputs to thalamic relay cells can be effectively divided into drivers and modulators. A number of features identify driver input, including having powerful, depressing synapses that activate only ionotropic receptors, being the major determinant of receptive field properties of the relay cell, and having singularly large terminals identified with the electron microscope as "RL" (for Round vesicle, Large terminal, and they form symmetric synapses; for details, see Sherman and Guillery, 1998, 2006;Sherman, 2005). A key for this study is that inputs to thalamus terminating in RL, or very large, terminals represent driver inputs. Modulators are associated with weaker, often facilitating synapses that activate ionotropic and metabotropic receptors, and they produce small synaptic terminals. Drivers represent the main information-bearing input to be relayed to cortex and define what is being relayed. For instance, the retinal input is the driver for relay cells of the lateral geniculate nucleus, because it is the retinal input, rather than brainstem or layer 6 cortical input, that represents the main information relayed through the lateral ...

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Section: Discussionmentioning

confidence: 83%

Section: Other Differences Between First Order and Higher Order Thalamentioning

confidence: 99%

mentioning

confidence: 99%

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Fewer driver synapses in higher order than in first order thalamic relays

Horn

Sherman

2007

Neuroscience

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“…DAT-IR has been reported in thalamus (Melchitzky and Lewis, 2001) and thalamic [ 11 C]cocaine accumulation was proposed to reflect DAT binding (Telang et al, 1999). Moreover, a very recent report described a significant dopaminergic innervation of the primate thalamus including a confirmation of widespread DAT-IR localization (Sanchez-Gonzalez et al, 2005). Thus, thalamic [ 11 C]altropane accumulation may reflect DAT-binding sites.…”

Section: Discussionmentioning

confidence: 99%

Cerebellar Vermis Involvement in Cocaine-Related Behaviors

Anderson

Maas

Frederick

et al. 2005

Neuropsychopharmacol

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Although the cerebellum is increasingly being viewed as a brain area involved in cognition, it typically is excluded from circuitry considered to mediate stimulant-associated behaviors since it is low in dopamine. Yet, the primate cerebellar vermis (lobules II-III and VIII-IX) has been reported to contain axonal dopamine transporter immunoreactivity (DAT-IR). We hypothesized that DAT-IR-containing vermis areas would be activated in cocaine abusers by cocaine-related cues and, in healthy humans, would accumulate DAT-selective ligands. We used BOLD fMRI to determine whether cocaine-related cues activated DAT-IR-enriched vermis regions in cocaine abusers and positron emission tomography imaging of healthy humans to determine whether the DAT-selective ligand [ 11 C]altropane accumulated in those vermis regions. Cocaine-related cues selectively induced BOLD activation in lobules II-III and VIII-IX in cocaine users, and, at early time points after ligand administration, we found appreciable [ 11 C]altropane accumulation in lobules VIII-IX, possibly indicating DAT presence in this region. These data suggest that parts of cerebellar vermis mediate cocaine's persisting and acute effects. In light of prior findings illustrating vermis connections to midbrain dopamine cell body regions, established roles for the vermis as a locus of sensorimotor integration and motor planning, and findings of increased vermis activation in substance abusers during reward-related and other cognitive tasks, we propose that the vermis be considered one of the structures involved in cocaine-and other incentive-related behaviors.

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“…Though DAT are found in both brain regions the concentration in cerebellum is low (Glaser et al, 2006;Sanchez-Gonzalez et al, 2005). However, DA regulation of metabolism in these brain regions could be indirect via striato-thalamic or striato-cerebellar pathways (Hoshi et al, 2005).…”

Section: Dat −/− Mice Have Significantly Greater Baseline Bglum Than mentioning

confidence: 99%

The effects of cocaine on regional brain glucose metabolism is attenuated in dopamine transporter knockout mice

Thanos

Michaelides

Benveniste

et al. 2008

Synapse

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Cocaine's ability to block the dopamine transporter (DAT) is crucial for its reinforcing effects. However the brain functional consequences of DAT blockade by cocaine are less clear since they are confounded by its concomitant blockade of norepinephrine and serotonin transporters. To separate the dopaminergic from the non-dopaminergic effects of cocaine on brain function we compared the regional brain metabolic responses to cocaine between dopamine transporter deficient (DAT −/− ) mice with that of their DAT +/+ littermates. We measured regional brain metabolism (marker of brain function) with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) and microPET (μPET) before and after acute cocaine administration (i.p. 10 mg/kg). Scans were conducted 2 weeks apart. At baseline DAT −/− mice had significantly greater metabolism in thalamus and cerebellum than DAT +/+ . Acute cocaine decreased whole brain metabolism and this effect was greater in DAT +/+ (15%) than in DAT −/− mice (5%). DAT +/+ mice showed regional decreases in the olfactory bulb, motor cortex, striatum, hippocampus, thalamus and cerebellum whereas DAT −/− mice showed decreases only in thalamus. The differential pattern of regional responses to cocaine in DAT −/− and DAT +/+ suggests that most of the brain metabolic changes from acute cocaine are due to DAT blockade. Cocaine-induced decreases in metabolism in thalamus (region with dense noradrenergic innervation) in DAT −/− suggest that these were mediated by cocaine's blockade of norepinephrine transporters. The greater baseline metabolism in DAT −/− than DAT +/+ mice in cerebellum (brain region mostly devoid of DAT) suggests that dopamine indirectly regulates activity of these brain regions.

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The Primate Thalamus Is a Key Target for Brain Dopamine

Cited by 258 publications

References 48 publications

Fewer driver synapses in higher order than in first order thalamic relays

Fewer driver synapses in higher order than in first order thalamic relays

Cerebellar Vermis Involvement in Cocaine-Related Behaviors

The effects of cocaine on regional brain glucose metabolism is attenuated in dopamine transporter knockout mice

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