Dataset Information

Neurotensin induces hypothermia by activating both neuronal neurotensin receptor 1 and astrocytic neurotensin receptor 2 in the median preoptic nucleus.

ABSTRACT: Neurotensin (NTS) is a neuropeptide acting as a neuromodulator in the brain and is a very potent hypothermic agent. However, the cellular mechanisms of actions are not fully understood. Here we report that NTS increases the firing rate of preoptic GABAergic neurons by activating both neurotensin receptor 1 (NTSR1) and neurotensin receptor 2 (NTSR2), expressed by neurons and astrocytes, respectively. Downstream of NTSR1 the neuropeptide activated an inward current, calcium release from intracellular stores and, postsynaptically, increased frequency and amplitude of inhibitory synaptic events. NTSR2 activation in astrocytes resulted in increased excitatory input in preoptic GABAergic neurons, an effect which was dependent upon the activation of P2X4 receptors. We also found that neuromedin N acted as a selective agonist at the NTSR1. Surprisingly, activation of both NTSR1 and NTSR2 in the median preoptic nucleus was required for activating a full hypothermic response.

SUBMITTER: Tabarean IV

PROVIDER: S-EPMC7274271 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Neurotensin induces hypothermia by activating both neuronal neurotensin receptor 1 and astrocytic neurotensin receptor 2 in the median preoptic nucleus.

Tabarean Iustin V IV

Neuropharmacology 20200408

Neurotensin (NTS) is a neuropeptide acting as a neuromodulator in the brain and is a very potent hypothermic agent. However, the cellular mechanisms of actions are not fully understood. Here we report that NTS increases the firing rate of preoptic GABAergic neurons by activating both neurotensin receptor 1 (NTSR1) and neurotensin receptor 2 (NTSR2), expressed by neurons and astrocytes, respectively. Downstream of NTSR1 the neuropeptide activated an inward current, calcium release from intracellu ...[more]

PMID: 32275927

Similar Datasets

Project description:To understand how sleep-wakefulness cycles are regulated, it is essential to disentangle structural and functional relationships between the preoptic area (POA) and lateral hypothalamic area (LHA), since these regions play important yet opposing roles in the sleep-wakefulness regulation. GABA- and galanin (GAL)-producing neurons in the ventrolateral preoptic nucleus (VLPO) of the POA (VLPOGABA and VLPOGAL neurons) are responsible for the maintenance of sleep, while the LHA contains orexin-producing neurons (orexin neurons) that are crucial for maintenance of wakefulness. Through the use of rabies virus-mediated neural tracing combined with in situ hybridization (ISH) in male and female orexin-iCre mice, we revealed that the vesicular GABA transporter (Vgat, Slc32a1)- and galanin (Gal)-expressing neurons in the VLPO directly synapse with orexin neurons in the LHA. A majority (56.3 ± 8.1%) of all VLPO input neurons connecting to orexin neurons were double-positive for Vgat and Gal Using projection-specific rabies virus-mediated tracing in male and female Vgat-ires-Cre and Gal-Cre mice, we discovered that VLPOGABA and VLPOGAL neurons that send projections to the LHA received innervations from similarly distributed input neurons in many brain regions, with the POA and LHA being among the main upstream areas. Additionally, we found that acute optogenetic excitation of axons of VLPOGABA neurons, but not VLPOGAL neurons, in the LHA of male Vgat-ires-Cre mice induced wakefulness. This study deciphers the connectivity between the VLPO and LHA, provides a large-scale map of upstream neuronal populations of VLPO→LHA neurons, and reveals a previously uncovered function of the VLPOGABA→LHA pathway in the regulation of sleep and wakefulness.SIGNIFICANCE STATEMENT We identified neurons in the ventrolateral preoptic nucleus (VLPO) that are positive for vesicular GABA transporter (Vgat) and/or galanin (Gal) and serve as presynaptic partners of orexin-producing neurons in the lateral hypothalamic area (LHA). We depicted monosynaptic input neurons of GABA- and galanin-producing neurons in the VLPO that send projections to the LHA throughout the entire brain. Their input neurons largely overlap, suggesting that they comprise a common neuronal population. However, acute excitatory optogenetic manipulation of the VLPOGABA→LHA pathway, but not the VLPOGAL→LHA pathway, evoked wakefulness. This study shows the connectivity of major components of the sleep/wake circuitry in the hypothalamus and unveils a previously unrecognized function of the VLPOGABA→LHA pathway in sleep-wakefulness regulation. Furthermore, we suggest the existence of subpopulations of VLPOGABA neurons that innervate LHA.

Dataset Information

Neurotensin induces hypothermia by activating both neuronal neurotensin receptor 1 and astrocytic neurotensin receptor 2 in the median preoptic nucleus.

Publications

Neurotensin induces hypothermia by activating both neuronal neurotensin receptor 1 and astrocytic neurotensin receptor 2 in the median preoptic nucleus.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets