Dopamine Differentially Modulates the Excitability of Striatal Neurons of the Direct and Indirect Pathways in Lamprey

Ericsson, Johan; Stephenson-Jones, Marcus; Pérez‐Fernández, Juan; Robertson, Brita; Silberberg, Gilad; Grillner, Sten

doi:10.1523/jneurosci.5881-12.2013

Cited by 54 publications

(61 citation statements)

References 38 publications

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“…Dopamine increases the excitability of striatal D1r-expressing neurons (Ericsson et al, 2013; Planert et al, 2013). Using optogenetc methods (Kravitz et al, 2012; Lobo et al, 2010), we first tested the hypothesis that artificial activation of D1r-neurones in dorsal striatum would substitute for sugar in its ability to promote sweet appetite in the absence of hunger.…”

Section: Resultsmentioning

confidence: 99%

Striatal Dopamine Links Gastrointestinal Rerouting to Altered Sweet Appetite

et al. 2016

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Reductions in calorie intake contribute significantly to the positive outcome of bariatric surgeries. However, the physiological mechanisms linking the rerouting of the gastrointestinal tract to reductions in sugar cravings remain uncertain. We show that a duodenal-jejunal bypass (DJB) intervention inhibits maladaptive sweet appetite by acting on dopamine-responsive striatal circuitries. DJB disrupted the ability of recurrent sugar exposure to promote sweet appetite in sated animals, thereby revealing a link between recurrent duodenal sugar influx and maladaptive sweet intake. Unlike ingestion of a low-calorie sweetener, ingestion of sugar was associated with significant dopamine effluxes in dorsal striatum, with glucose infusions into the duodenum inducing greater striatal dopamine release than equivalent jejunal infusions. Consistently, optogenetic activation of dopamine-excitable cells of dorsal striatum was sufficient to restore maladaptive sweet appetite in sated DJB mice. Our findings point to a causal link between striatal dopamine signaling and the outcomes of bariatric interventions.

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Section: Resultsmentioning

confidence: 99%

Striatal Dopamine Links Gastrointestinal Rerouting to Altered Sweet Appetite

et al. 2016

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“…Over seconds to minutes, elevated “tonic” dopamine tends to enhance the excitability of direct pathway (“GO”) MSNs via D1 receptors, while reducing excitability of indirect pathway (“NO-GO”) MSNs via D2 receptors [24,96,97]. Briefer “phasic” changes in dopamine modulate synaptic plasticity to create persistent changes in behavior [98,99].…”

Section: Discussionmentioning

confidence: 99%

Dissociable effects of dopamine on learning and performance within sensorimotor striatum

et al. 2014

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Striatal dopamine is an important modulator of current behavior, as seen in the rapid and dramatic effects of dopamine replacement therapy in Parkinson Disease (PD). Yet there is also extensive evidence that dopamine acts as a learning signal, modulating synaptic plasticity within striatum to affect future behavior. Disentangling these “performance” and “learning” functions is important for designing effective, long-term PD treatments. We conducted a series of unilateral drug manipulations and dopamine terminal lesions in the dorsolateral striatum of rats highly-trained to perform brief instructed head/neck movements (two-alternative forced choice task). Reaction times and accuracy were measured longitudinally to determine if task behavior changed immediately, progressed over time, and/or persisted after drug withdrawal. Enhanced dopamine signaling with amphetamine caused an immediate, nonprogressive, and bilateral decrease in reaction times (RT). The altered RT distributions were consistent with reduced distance to threshold in the linear approach to threshold with ergodic rate (LATER) model of decision-making. Conversely, the dopamine antagonist flupenthixol caused experience-dependent, persistent changes in RT and accuracy indicative of a “learning” effect. These RT distributions were consistent with a slowed rate of approach to decision threshold. Our results show that dopaminergic signaling makes dissociable contributions to current and future behavior even within a single striatal subregion, and provide important clues for both models of normal decision-making and the design of novel drug therapies in PD.

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“…13). Those receptors are also present in lampreys (14,15). Targeted blocking of D1 receptors in the MLR ( control), locomotor frequency (−32.2 ± 6.3%; P < 0.001), and the number of locomotor cycles (−60.0 ± 9.9%; P < 0.001).…”

Section: Significancementioning

confidence: 99%

Forebrain dopamine neurons project down to a brainstem region controlling locomotion

Ryczko

Grätsch

Auclair

et al. 2013

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

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The contribution of dopamine (DA) to locomotor control is traditionally attributed to ascending dopaminergic projections from the substantia nigra pars compacta and the ventral tegmental area to the basal ganglia, which in turn project down to the mesencephalic locomotor region (MLR), a brainstem region controlling locomotion in vertebrates. However, a dopaminergic innervation of the pedunculopontine nucleus, considered part of the MLR, was recently identified in the monkey. The origin and role of this dopaminergic input are unknown. We addressed these questions in a basal vertebrate, the lamprey. Here we report a functional descending dopaminergic pathway from the posterior tuberculum (PT; homologous to the substantia nigra pars compacta and/or ventral tegmental area of mammals) to the MLR. By using triple labeling, we found that dopaminergic cells from the PT not only project an ascending pathway to the striatum, but send a descending projection to the MLR. In an isolated brain preparation, PT stimulation elicited excitatory synaptic inputs into patch-clamped MLR cells, accompanied by activity in reticulospinal cells. By using voltammetry coupled with electrophysiological recordings, we demonstrate that PT stimulation evoked DA release in the MLR, together with the activation of reticulospinal cells. In a semi-intact preparation, stimulation of the PT elicited reticulospinal activity together with locomotor movements. Microinjections of a D1 antagonist in the MLR decreased the locomotor output elicited by PT stimulation, whereas injection of DA had an opposite effect. It appears that this descending dopaminergic pathway has a modulatory role on MLR cells that are known to receive glutamatergic projections and promotes locomotor output.motor system | Parkinson disease D opamine (DA) neurons of the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) modulate motor behaviors, including locomotion, through ascending projections to the basal ganglia, the output of which projects to the mesencephalic locomotor region (MLR) (1-3), a brainstem region known to control locomotion in all vertebrate species tested to date (reviewed in ref. 4). DA is known to control the excitability of striatal cells, and a dysfunction of the ascending DA pathway to the striatum is considered to be the main cause for the motor deficits in Parkinson disease (1). However, there have been hints of descending DA projections that would be in position to directly modulate the MLR and hence locomotor activity. In monkeys, DA terminals of unknown origin were observed in the pedunculopontine nucleus (PPN) (5), considered part of the MLR (reviewed in ref. 4). In addition, there is an axonal projection from the SNc to the PPN in rats, but the transmitter system is unknown (6).We examined the DA system in a basal vertebrate, the lamprey, and found a previously unknown descending DA pathway from the posterior tuberculum (PT) to the MLR, which comprises the PPN and the laterodorsal tegmental nucleus (LDT) in lampreys (ref. 7; reviewed...

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Dopamine Differentially Modulates the Excitability of Striatal Neurons of the Direct and Indirect Pathways in Lamprey

Cited by 54 publications

References 38 publications

Striatal Dopamine Links Gastrointestinal Rerouting to Altered Sweet Appetite

Striatal Dopamine Links Gastrointestinal Rerouting to Altered Sweet Appetite

Dissociable effects of dopamine on learning and performance within sensorimotor striatum

Forebrain dopamine neurons project down to a brainstem region controlling locomotion

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