Cholinergic neurons expressing neuromedin K receptor (NK3) in the basal forebrain of the rat: a double immunofluorescence study

Chen, L.-W; Wei, Lichun; Liu, Tianshuai; Ding, Yu; Zhang, H; Rao, Zhi-Ren; Ju, Gong; Chan, Ying-Shing

doi:10.1016/s0306-4522(00)00568-6

Cited by 23 publications

(12 citation statements)

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“…Because Chen et al (2001) reported that all NK3 receptorimmunoreactive neurons in the SI or basal nucleus of Meynert exhibited ChAT immunoreactivity, we next examined the colocalization of ChAT and NK3 receptor in single neurons of the basal forebrain region. In the rat brain fixed as described in Materials and Methods, although the majority (89%) of NK3 receptor-immunoreactive neurons were immunoreactive for ChAT in the HLDB (Figs.…”

Section: Chemical Characteristics Of Nk3 Receptorexpressing Neurons Imentioning

confidence: 99%

“…Inversely, about 1% and 5% of ChAT-positive neurons in the SI/VP and GPe, respectively, were immunoreactive for NK3 receptor. In an attempt to reproduce the previous results of Chen et al (2001), the rats were perfused with 4% paraformaldehyde in 0.1 M phosphate buffer, and ChAT was immunostained with anti-ChAT mouse antibody (clone # 1.B3.9B3) as described by them. Because the concentration (1:500-diluted, 0.1 g/ml) of the anti-ChAT antibody used in their study was too low to show clear ChAT immunoreactivity, we employed a higher concentration (1 g/ml) for doubleimmunofluorescence staining.…”

Section: Chemical Characteristics Of Nk3 Receptorexpressing Neurons Imentioning

confidence: 99%

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GABAergic basal forebrain neurons that express receptor for neurokinin B and send axons to the cerebral cortex

Furuta

Koyano

Tomioka

et al. 2004

J of Comparative Neurology

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Neurons expressing neurokinin B (NK3) receptor in the basal forebrain region of rats were characterized histochemically by combining immunocytochemistry, in situ hybridization and retrograde labeling, and electrophysiologically by whole-cell clamp recording. NK3 receptor-immunoreactive neurons were found in the basal forebrain region including the substantia innominata, where axon terminals immunoreactive for preprotachykinin B, the precursor peptide of neurokinin B (NKB), were densely distributed. More than 90% of NK3 receptor-expressing neurons in the basal forebrain region showed signals for glutamate decarboxylase mRNA, indicating that almost all NK3 receptor-expressing neurons were gamma-aminobutyric acid (GABA)ergic neurons. On the other hand, only a few NK3 receptor-immunoreactive neurons showed immunoreactivity for choline acetyltransferase or parvalbumin in the substantia innominata, ventral pallidum, and globus pallidus, although the distribution of NK3 receptor-expressing neurons overlapped with those of cholinergic neurons and parvalbumin-positive neurons. After injection of wheat germ agglutinin into the cerebral cortex, NK3 receptor immunoreactivity was detected in about 25% of retrogradely labeled basal forebrain neurons, indicating that NK3 receptor-expressing neurons send projection fibers to the cerebral cortex. In the whole-cell clamp recording study, a selective NK3 receptor agonist evoked membrane depolarization or inward currents with decrease of input impedance in 10 of 100 cortically projecting neurons recorded in the basal forebrain region. Because NKB-producing striatal neurons send axons selectively to the basal forebrain region, the present results suggest that the release of NKB by those striatal neurons induces an inhibitory effect on cortical neurons via facilitation of GABAergic basal forebrain neurons expressing NK3 receptor.

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Section: Chemical Characteristics Of Nk3 Receptorexpressing Neurons Imentioning

confidence: 99%

Section: Chemical Characteristics Of Nk3 Receptorexpressing Neurons Imentioning

confidence: 99%

GABAergic basal forebrain neurons that express receptor for neurokinin B and send axons to the cerebral cortex

Furuta

Koyano

Tomioka

et al. 2004

J of Comparative Neurology

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“…This effect was NK3-R specific because it was completely blocked by an NK3-R antagonist. NK3 receptors are located on cholinergic neurons (11,12), and the activity of the cholinergic system can be stimulated by NK3-R agonism in adult animals (14). Although one cannot rule out that the increase in cholinergic activity is due to an indirect activation of cholinergic cells of the basal forebrain, it is possible that such an effect is the consequence of an excitatory activation of these cells by a direct action on NK3-Rs located on cell bodies of cholinergic cells of the basal forebrain.…”

Section: Discussionmentioning

confidence: 99%

“…There is a close interaction between NK3-R and the cholinergic system. NK3-R are localized on cholinacetyltransferase-containing neurons in the basal forebrain (12), and the activity of the septo-hippocampal cholinergic system was found to be stimulated by NK3-R agonists in adult animals (13,14). An involvement of NK3-Rs in learning and memory processes has also been indicated in rats and mice (14)(15)(16)(17).…”

Section: Senktide | In Vivo Microdialysismentioning

confidence: 96%

Neurokinin3 receptor as a target to predict and improve learning and memory in the aged organism

Silva

Lenz

Rotter

et al. 2013

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

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Impaired learning and memory performance is often found in aging as an early sign of dementia. It is associated with neuronal loss and reduced functioning of cholinergic networks. Here we present evidence that the neurokinin3 receptors (NK3-R) and their influence on acetylcholine (ACh) release may represent a crucial mechanism that underlies age-related deficits in learning and memory. Repeated pharmacological stimulation of NK3-R in aged rats was found to improve learning in the water maze and in object-place recognition. This treatment also enhanced in vivo acetylcholinergic activity in the frontal cortex, hippocampus, and amygdala but reduced NK3-R mRNA expression in the hippocampus. Furthermore, NK3-R agonism incurred a significantly higher increase in ACh levels in aged animals that showed superior learning than in those that were most deficient in learning. Our findings suggest that the induced activation of ACh, rather than basal ACh activity, is associated with superior learning in the aged. To test whether natural variation in NK3-R function also determines learning and memory performance in aged humans, we investigated 209 elderly patients with cognitive impairments. We found that of the 15 analyzed single single-nucleotide ploymorphism (SNPs) of the NK3-R-coding gene, TACR3, the rs2765 SNP predicted the degree of impairment of learning and memory in these patients. This relationship could be partially explained by a reduced right hippocampus volume in a subsample of 111 tested dementia patients. These data indicate the NK3-R as an important target to predict and improve learning and memory performance in the aged organism. senktide | in vivo microdialysis H umans exhibit a decline in cognitive capacity with age, which may progressively lead to dementia (1). Age-dependent morphological and physiological changes within the cholinergic system of the brain have been described as a major mechanism underlying impairments of learning and memory (2, 3). Numerous studies in aged rats have revealed that a degeneration of cholinergic neurons in the basal forebrain is associated with learning and >memory deficits (4). Likewise, the consistent correlations found between cholinergic degeneration and cognitive impairments indicate a high correspondence between acetylcholinergic activity and the magnitude of cognitive decline (4-6). This relationship has also been shown in patients with Alzheimer's disease (7,8).The neuropeptide neurokinins (NKs) substance P, neurokinin A, neurokinin B (NK-B), neuropeptide K, neuropeptide γ, and hemokinin 1 bind to the three known NK-receptors (NK3-R) (NK1-, NK2-, and NK3-R) with different degrees of affinity, whereby NK-B is the preferred ligand to NK3-R (9). NK3-Rs are widespread in the brain, including areas that are implicated in processes governing learning and memory such as the hippocampus, frontal cortex (FC), and medial septum (10, 11). There is a close interaction between NK3-R and the cholinergic system. NK3-R are localized on cholinacetyltransferase-containing neurons in ...

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“…NK3 receptors are found in brain areas implicated in learning and memory, including hippocampus, frontal cortex, and medial septum (Shughrue et al, 1996). The NK3 receptor is related to cholinergic activity, with the expression of the receptor on choline acetyltransferaseepositive neurons of the basal forebrain (BF) (Chen et al, 2001) and stimulation of the activity of the septo-hippocampal cholinergic system by agonists of the NK3 receptor in adult animals (Schäble et al, 2012). Application of NK3 has been found to prevent N-methyl D aspartateeinduced lowering of choline acetyltransferase activity in the BF in rats (Wenk et al, 1997) and to increase the release of acetylcholine in amygdala and hippocampus in animal models (Morozova et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Association of a neurokinin 3 receptor polymorphism with the anterior basal forebrain

Teipel

Grothe

Wittfeld

et al. 2015

Neurobiology of Aging

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Cholinergic neurons expressing neuromedin K receptor (NK3) in the basal forebrain of the rat: a double immunofluorescence study

Cited by 23 publications

References 53 publications

GABAergic basal forebrain neurons that express receptor for neurokinin B and send axons to the cerebral cortex

GABAergic basal forebrain neurons that express receptor for neurokinin B and send axons to the cerebral cortex

Neurokinin3 receptor as a target to predict and improve learning and memory in the aged organism

Association of a neurokinin 3 receptor polymorphism with the anterior basal forebrain

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