Transient expression of neuropeptide W in postnatal mouse hypothalamus – A putative regulator of energy homeostasis

Motoike, Toshiyuki; Skach, Amber; Godwin, Jackie; Sinton, Christopher M.; Yamazaki, Maya; Abe, Manabu; Natsume, Rie; Sakimura, Kenji; Yanagisawa, Masashi

doi:10.1016/j.neuroscience.2015.06.014

Cited by 9 publications

(6 citation statements)

References 62 publications

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“…However, we were unable to detect any distinct expression of NPW mRNA in the adult hippocampus using colorimetric in situ hybridization (40). Furthermore, we detected NPW immunoreactivity only in the BSTL and CeAL but not in the target regions of CA3 pyramidal neurons, such as the lateral septal nucleus, CA1, and CA3 regions.…”

Section: Discussioncontrasting

confidence: 60%

Mesolimbic neuropeptide W coordinates stress responses under novel environments

Motoike

Long

Tanaka

et al. 2016

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

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Neuropeptide B (NPB) and neuropeptide W (NPW) are endogenous neuropeptide ligands for the G protein-coupled receptors NPBWR1 and NPBWR2. Here we report that the majority of NPW neurons in the mesolimbic region possess tyrosine hydroxylase immunoreactivity, indicating that a small subset of dopaminergic neurons coexpress NPW. These NPW-containing neurons densely and exclusively innervate two limbic system nuclei in adult mouse brain: the lateral bed nucleus of the stria terminalis and the lateral part of the central amygdala nucleus (CeAL). In the CeAL of wild-type mice, restraint stress resulted in an inhibition of cellular activity, but this stressinduced inhibition was attenuated in the CeAL neurons of NPW −/− mice. Moreover, the response of NPW −/− mice to either formalininduced pain stimuli or a live rat (i.e., a potential predator) was abnormal only when they were placed in a novel environment: The mice failed to show the normal species-specific self-protective and aversive reactions. In contrast, the behavior of NPW −/− mice in a habituated environment was indistinguishable from that of wildtype mice. These results indicate that the NPW/NPBWR1 system could play a critical role in the gating of stressful stimuli during exposure to novel environments.L imbic structures, including the amygdala and bed nucleus of the stria terminalis (BST), where different modalities of environmental stimuli can converge and interact, are critical for the response to stress (1). The basolateral amygdala (BLA) receives sensory information from the thalamus and cortex and transfers that information to the central amygdala (CeA), an output center for the amygdaloid complex. Subsequently, the CeA relays this information through axonal projections to nuclei in diverse areas, such as the hypothalamus, brainstem, and pons (2, 3). These circuits are essential for mediating fear and anxiety, especially for fear conditioning using auditory or visual conditioned stimuli (4, 5). Indeed, in a recent report, optogenetic manipulation of the BLA-CeA pathway was found to modulate the expression of anxiety in the mouse (6).The lateral BST (BSTL) and CeA (CeAL) are two major components of the central extended amygdala, a continuum of telencephalic structures of the forebrain (7,8). Both the BSTL and CeAL contain numerous GABAergic as well as peptidergic neurons, such as those producing enkephalin, corticotropin-releasing factor, and somatostatin (9-13); these GABAergic neurons form dense local inhibitory circuits within these nuclei. The GABAergic microcircuit in the CeAL is thought to play pivotal roles in mediating fear and anxiety, as recently dissected at the cellular level by studies that combined optogenetics and electrophysiology (14-17). A subpopulation of GABAergic neurons in the CeAL, which is inhibited by a conditioned stimulus (CS), is differentiated by the expression PKCδ (14). These PKCδ + GABAergic neurons were shown to provide feed-forward disinhibition on output neurons in the medial CeA (CeAM), resulting in a conditioned freezi...

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Section: Discussioncontrasting

confidence: 60%

Mesolimbic neuropeptide W coordinates stress responses under novel environments

Motoike

Long

Tanaka

et al. 2016

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

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“…Here, we assigned 27 neuropeptides slecifically to GABA, glutamate and dopamine neuronal subtypes ( Figure 2c,d and ED3b-e ). Our data demonstrate a transient increase in e.g., Sst , Tac1 , Bdnf , Adcyap1 , Pnoc , Nmu , Trh in juvenile mice (P10) 21 ( Figure 2c ) along with the rapid induction of their cognate receptors during the early postnatal window ( Figure 2d ). Finally, we used Oxtr Venus/+ mice to demonstrate that the onset of Venus expression (used as a surrogate for Oxtr ) in e.g., Pomc + neurons in Arc 22 , DMH and VMH is ~E18 with a gradual increase postnatally ( Figure 2e , ED3f ).…”

Section: Resultsmentioning

confidence: 63%

Molecular design of hypothalamus development

Romanov

Tretiakov

Kastriti

et al. 2020

Nature

120

165

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A wealth of specialized neuroendocrine command systems intercalated within the hypothalamus control the most fundamental physiological needs 1 , 2 . Nevertheless, a developmental blueprint integrating molecular determinants of neuronal and glial diversity along temporal and spatial scales of hypothalamus development remains unresolved 3 . Here, we combine single-cell RNA-seq on 51,199 cells of ectodermal origin, gene regulatory network (GRN) screens in conjunction with GWAS-based disease phenotyping and genetic lineage reconstruction to show that 9 glial and 33 neuronal subtypes are generated by mid-gestation under the control of distinct GRNs. Combinatorial molecular codes arising from neurotransmitters, neuropeptides and transcription factors are minimally required to decode the taxonomical hierarchy of hypothalamic neurons. Differentiation of GABA and dopamine but not glutamate neurons relies on quasi-stable intermediate states with a pool of GABA progenitors giving rise to dopamine cells 4 . An unexpected abundance of chemotropic proliferation and guidance cues commonly implicated in dorsal (cortical) patterning 5 was found in the hypothalamus. Particularly, Slit / Robo loss-of-function impacted both the production and positioning of periventricular dopamine neurons. Overall, we uncover molecular principles shaping the developmental architecture of the hypothalamus and show how neuronal heterogeneity is transformed into a multimodal neural unit to endow a virtually infinite adaptive potential throughout life.

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“…(3) LHA GABA cluster 2 selectively expresses Npy (encoding neuropeptide Y), Npw and Ebf1. Previous work had identified a population of glucose-sensitive Npy-expressing LHA neurons 10 as well as Npy and Npw co-expressing neurons in the DMH and LHA 11 . In the latter study, coexpression peaked over the first three postnatal weeks but declined after P28.…”

Section: And 12)mentioning

confidence: 99%