Neurokinin-1 and neurokinin-3 receptors in primate substantia nigra

Lévesque, Martin; Wallman, Marie‐Josée; Parent, Rémy; Sı́k, Attila; Parent, André

doi:10.1016/j.neures.2006.11.002

Cited by 20 publications

(11 citation statements)

References 51 publications

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“…Together, these results suggest that NK 1 and NK 3 receptors have locations conducive to tachykinin modulation of both GABAergic and dopaminergic mesocorticolimbic pathways in the rat VTA. The independent detection of NK 1 and NK 3 receptors in each of the two primary output from VTA neurons also suggests that at least some of these neurons may co-express both tachykinin receptor subtypes; as previously described in enteric neurons (Schmidlin et al, 2002) or primate substantia nigra (Levesque et al, 2007). …”

Section: Discussionsupporting

confidence: 61%

The neurokinin‐3 (NK₃) and the neurokinin‐1 (NK₁) receptors are differentially targeted to mesocortical and mesolimbic projection neurons and to neuronal nuclei in the rat ventral tegmental area

Lessard

Savard

Gobeil

et al. 2009

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Tonic activation of neurokinin-3 (NK3) receptors in dopamine neurons of the ventral tegmental area (VTA) has been implicated in the pathophysiology of schizophrenia. This psychiatric disorder is associated with a dysfunctional activity in VTA projection neurons that can affect cognitive function at the level of the medial prefrontal cortex (mPFC) as well as motor and motivational states controlled in part by mesolimbic output to the nucleus accumbens (Acb). To determine the relevant sites for NK3 receptor activation within this neuronal network, we used confocal and electron microscopy to examine NK3 receptors (Cy5; immunogold) and retrograde labeling of fluorogold (FG, FITC; immunoperoxidase) in the VTA of rats receiving either Acb or mPFC injections of FG. Comparison was made with neurokinin-1 (NK1) receptors, which are also present, but less abundant then NK3 receptors, in dopaminergic and GABAergic VTA neurons. There were no observable differences between NK3 and NK1 receptors in their primary locations in the cytoplasm and on the plasma membrane of VTA somata and dendrites with or without FG. Dendrites labeled with FG retrogradely transported from mPFC, however, contained more NK3 or less NK1 immunogold particles (plasmalemmal + cytoplasmic) then those retrogradely labeled following FG injection in the Acb. Moreover, only the NK3 receptors were detected in neuronal nuclei in the VTA and in the nuclei of human HEK-293T NK3-transfected cells. The enrichment of NK3 receptors in mesocortical projection neurons and nuclear distribution of these receptors may provide insight for understanding the selective antipsychotic effectiveness of NK3 antagonists.

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Section: Discussionsupporting

confidence: 61%

The neurokinin‐3 (NK₃) and the neurokinin‐1 (NK₁) receptors are differentially targeted to mesocortical and mesolimbic projection neurons and to neuronal nuclei in the rat ventral tegmental area

Lessard

Savard

Gobeil

et al. 2009

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“…Since substance P is frequently co-released with GABA in the substantia nigra29, we further measured the levels of this neuropeptide in the dialysate samples. As for GABA, the levels of KCl-induced substance P release were higher in PrP 0/0 than WT mice (Fig.…”

Section: Resultsmentioning

confidence: 99%

A PrPC-caveolin-Lyn complex negatively controls neuronal GSK3β and serotonin 1B receptor

Hernandez-Rapp

Martin-Lannerée

Hirsch

et al. 2014

Sci Rep

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The cellular prion protein, PrPC, is a glycosylphosphatidylinositol-anchored protein, abundant in lipid rafts and highly expressed in the brain. While PrPC is much studied for its involvement under its abnormal PrPSc isoform in Transmissible Spongiform Encephalopathies, its physiological role remains unclear. Here, we report that GSK3β, a multifunctional kinase whose inhibition is neuroprotective, is a downstream target of PrPC signalling in serotonergic neuronal cells. We show that the PrPC-dependent inactivation of GSK3β is relayed by a caveolin-Lyn platform located on neuronal cell bodies. Furthermore, the coupling of PrPC to GSK3β potentiates serotonergic signalling by altering the distribution and activity of the serotonin 1B receptor (5-HT1BR), a receptor that limits neurotransmitter release. In vivo, our data reveal an increased GSK3β kinase activity in PrP-deficient mouse brain, as well as sustained 5-HT1BR activity, whose inhibition promotes an anxiogenic behavioural response. Collectively, our data unveil a new facet of PrPC signalling that strengthens neurotransmission.

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“…Such SP release from the axon terminals of MSPNs projecting to SNr can excite the comingled dendrites of DA cells (Condé, 1992;Otsuka and Yoshioka, 1993;Hanson et al, 2002;Martorana et al, 2003;Betarbet and Greenamyre, 2004) via neurokinin receptors (Whitty et al, 1997;Lévesque et al, 2007). Beaujouan et al (2004) reported activity-dependent release of SP from striatonigral terminals, and SP released intranigrally increases striatal dopamine release (Reid et al, 1990;Khan et al, 1996).…”

Section: Methodsmentioning

confidence: 99%

A Local Circuit Model of Learned Striatal and Dopamine Cell Responses under Probabilistic Schedules of Reward

Tan

Bullock

2008

J. Neurosci.

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Neurokinin-1 and neurokinin-3 receptors in primate substantia nigra

Cited by 20 publications

References 51 publications

The neurokinin‐3 (NK₃) and the neurokinin‐1 (NK₁) receptors are differentially targeted to mesocortical and mesolimbic projection neurons and to neuronal nuclei in the rat ventral tegmental area

The neurokinin‐3 (NK₃) and the neurokinin‐1 (NK₁) receptors are differentially targeted to mesocortical and mesolimbic projection neurons and to neuronal nuclei in the rat ventral tegmental area

A PrPC-caveolin-Lyn complex negatively controls neuronal GSK3β and serotonin 1B receptor

A Local Circuit Model of Learned Striatal and Dopamine Cell Responses under Probabilistic Schedules of Reward

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Neurokinin-1 and neurokinin-3 receptors in primate substantia nigra

Cited by 20 publications

References 51 publications

The neurokinin‐3 (NK3) and the neurokinin‐1 (NK1) receptors are differentially targeted to mesocortical and mesolimbic projection neurons and to neuronal nuclei in the rat ventral tegmental area

The neurokinin‐3 (NK3) and the neurokinin‐1 (NK1) receptors are differentially targeted to mesocortical and mesolimbic projection neurons and to neuronal nuclei in the rat ventral tegmental area

A PrPC-caveolin-Lyn complex negatively controls neuronal GSK3β and serotonin 1B receptor

A Local Circuit Model of Learned Striatal and Dopamine Cell Responses under Probabilistic Schedules of Reward

Contact Info

Product

Resources

About

The neurokinin‐3 (NK₃) and the neurokinin‐1 (NK₁) receptors are differentially targeted to mesocortical and mesolimbic projection neurons and to neuronal nuclei in the rat ventral tegmental area

The neurokinin‐3 (NK₃) and the neurokinin‐1 (NK₁) receptors are differentially targeted to mesocortical and mesolimbic projection neurons and to neuronal nuclei in the rat ventral tegmental area