Chemogenetic modulation of histaminergic neurons in the tuberomamillary nucleus alters territorial aggression and wakefulness

Abstract Designer receptor activated by designer drugs (DREADDs) techniques are widely used to modulate the activities of specific neuronal populations during behavioural tasks. However, DREADDs-induced modulation of histaminergic neurons in the tuberomamillary nucleus (HATMN neurons) has produced i...

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Autores principales: Fumito Naganuma, Tadaho Nakamura, Hiroshi Kuroyanagi, Masato Tanaka, Takeo Yoshikawa, Kazuhiko Yanai, Nobuyuki Okamura
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/1f9e12f39843402183a0d3fe3debd20f
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spelling oai:doaj.org-article:1f9e12f39843402183a0d3fe3debd20f2021-12-02T18:03:05ZChemogenetic modulation of histaminergic neurons in the tuberomamillary nucleus alters territorial aggression and wakefulness10.1038/s41598-021-95497-32045-2322https://doaj.org/article/1f9e12f39843402183a0d3fe3debd20f2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95497-3https://doaj.org/toc/2045-2322Abstract Designer receptor activated by designer drugs (DREADDs) techniques are widely used to modulate the activities of specific neuronal populations during behavioural tasks. However, DREADDs-induced modulation of histaminergic neurons in the tuberomamillary nucleus (HATMN neurons) has produced inconsistent effects on the sleep–wake cycle, possibly due to the use of Hdc-Cre mice driving Cre recombinase and DREADDs activity outside the targeted region. Moreover, previous DREADDs studies have not examined locomotor activity and aggressive behaviours, which are also regulated by brain histamine levels. In the present study, we investigated the effects of HATMN activation and inhibition on the locomotor activity, aggressive behaviours and sleep–wake cycle of Hdc-Cre mice with minimal non-target expression of Cre-recombinase. Chemoactivation of HATMN moderately enhanced locomotor activity in a novel open field. Activation of HATMN neurons significantly enhanced aggressive behaviour in the resident–intruder test. Wakefulness was increased and non-rapid eye movement (NREM) sleep decreased for an hour by HATMN chemoactivation. Conversely HATMN chemoinhibition decreased wakefulness and increased NREM sleep for 6 h. These changes in wakefulness induced by HATMN modulation were related to the maintenance of vigilance state. These results indicate the influences of HATMN neurons on exploratory activity, territorial aggression, and wake maintenance.Fumito NaganumaTadaho NakamuraHiroshi KuroyanagiMasato TanakaTakeo YoshikawaKazuhiko YanaiNobuyuki OkamuraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Fumito Naganuma
Tadaho Nakamura
Hiroshi Kuroyanagi
Masato Tanaka
Takeo Yoshikawa
Kazuhiko Yanai
Nobuyuki Okamura
Chemogenetic modulation of histaminergic neurons in the tuberomamillary nucleus alters territorial aggression and wakefulness
description Abstract Designer receptor activated by designer drugs (DREADDs) techniques are widely used to modulate the activities of specific neuronal populations during behavioural tasks. However, DREADDs-induced modulation of histaminergic neurons in the tuberomamillary nucleus (HATMN neurons) has produced inconsistent effects on the sleep–wake cycle, possibly due to the use of Hdc-Cre mice driving Cre recombinase and DREADDs activity outside the targeted region. Moreover, previous DREADDs studies have not examined locomotor activity and aggressive behaviours, which are also regulated by brain histamine levels. In the present study, we investigated the effects of HATMN activation and inhibition on the locomotor activity, aggressive behaviours and sleep–wake cycle of Hdc-Cre mice with minimal non-target expression of Cre-recombinase. Chemoactivation of HATMN moderately enhanced locomotor activity in a novel open field. Activation of HATMN neurons significantly enhanced aggressive behaviour in the resident–intruder test. Wakefulness was increased and non-rapid eye movement (NREM) sleep decreased for an hour by HATMN chemoactivation. Conversely HATMN chemoinhibition decreased wakefulness and increased NREM sleep for 6 h. These changes in wakefulness induced by HATMN modulation were related to the maintenance of vigilance state. These results indicate the influences of HATMN neurons on exploratory activity, territorial aggression, and wake maintenance.
format article
author Fumito Naganuma
Tadaho Nakamura
Hiroshi Kuroyanagi
Masato Tanaka
Takeo Yoshikawa
Kazuhiko Yanai
Nobuyuki Okamura
author_facet Fumito Naganuma
Tadaho Nakamura
Hiroshi Kuroyanagi
Masato Tanaka
Takeo Yoshikawa
Kazuhiko Yanai
Nobuyuki Okamura
author_sort Fumito Naganuma
title Chemogenetic modulation of histaminergic neurons in the tuberomamillary nucleus alters territorial aggression and wakefulness
title_short Chemogenetic modulation of histaminergic neurons in the tuberomamillary nucleus alters territorial aggression and wakefulness
title_full Chemogenetic modulation of histaminergic neurons in the tuberomamillary nucleus alters territorial aggression and wakefulness
title_fullStr Chemogenetic modulation of histaminergic neurons in the tuberomamillary nucleus alters territorial aggression and wakefulness
title_full_unstemmed Chemogenetic modulation of histaminergic neurons in the tuberomamillary nucleus alters territorial aggression and wakefulness
title_sort chemogenetic modulation of histaminergic neurons in the tuberomamillary nucleus alters territorial aggression and wakefulness
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/1f9e12f39843402183a0d3fe3debd20f
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