Lateral hypothalamic fast-spiking parvalbumin neurons modulate nociception through connections in the periaqueductal gray area

Abstract A pivotal role of the lateral hypothalamus (LH) in regulating appetitive and reward-related behaviors has been evident for decades. However, the contributions of LH circuits to other survival behaviors have been less explored. Here we examine how lateral hypothalamic neurons that express th...

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Autores principales:	Justin N. Siemian, Cara B. Borja, Sarah Sarsfield, Alexandre Kisner, Yeka Aponte
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d0a594f60e23400196e7204bf33e03e1
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spelling	oai:doaj.org-article:d0a594f60e23400196e7204bf33e03e12021-12-02T15:08:48ZLateral hypothalamic fast-spiking parvalbumin neurons modulate nociception through connections in the periaqueductal gray area10.1038/s41598-019-48537-y2045-2322https://doaj.org/article/d0a594f60e23400196e7204bf33e03e12019-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-48537-yhttps://doaj.org/toc/2045-2322Abstract A pivotal role of the lateral hypothalamus (LH) in regulating appetitive and reward-related behaviors has been evident for decades. However, the contributions of LH circuits to other survival behaviors have been less explored. Here we examine how lateral hypothalamic neurons that express the calcium-binding protein parvalbumin (PVALB; LHPV neurons), a small cluster of neurons within the LH glutamatergic circuitry, modulate nociception in mice. We find that photostimulation of LHPV neurons suppresses nociception to an acute, noxious thermal stimulus, whereas photoinhibition potentiates thermal nociception. Moreover, we demonstrate that LHPV axons form functional excitatory synapses on neurons in the ventrolateral periaqueductal gray (vlPAG), and photostimulation of these axons mediates antinociception to both thermal and chemical visceral noxious stimuli. Interestingly, this antinociceptive effect appears to occur independently of opioidergic mechanisms, as antagonism of μ-opioid receptors with systemically-administered naltrexone does not abolish the antinociception evoked by activation of this LHPV→vlPAG pathway. This study directly implicates LHPV neurons in modulating nociception, thus expanding the repertoire of survival behaviors regulated by LH circuits.Justin N. SiemianCara B. BorjaSarah SarsfieldAlexandre KisnerYeka AponteNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-10 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Justin N. Siemian Cara B. Borja Sarah Sarsfield Alexandre Kisner Yeka Aponte Lateral hypothalamic fast-spiking parvalbumin neurons modulate nociception through connections in the periaqueductal gray area
description	Abstract A pivotal role of the lateral hypothalamus (LH) in regulating appetitive and reward-related behaviors has been evident for decades. However, the contributions of LH circuits to other survival behaviors have been less explored. Here we examine how lateral hypothalamic neurons that express the calcium-binding protein parvalbumin (PVALB; LHPV neurons), a small cluster of neurons within the LH glutamatergic circuitry, modulate nociception in mice. We find that photostimulation of LHPV neurons suppresses nociception to an acute, noxious thermal stimulus, whereas photoinhibition potentiates thermal nociception. Moreover, we demonstrate that LHPV axons form functional excitatory synapses on neurons in the ventrolateral periaqueductal gray (vlPAG), and photostimulation of these axons mediates antinociception to both thermal and chemical visceral noxious stimuli. Interestingly, this antinociceptive effect appears to occur independently of opioidergic mechanisms, as antagonism of μ-opioid receptors with systemically-administered naltrexone does not abolish the antinociception evoked by activation of this LHPV→vlPAG pathway. This study directly implicates LHPV neurons in modulating nociception, thus expanding the repertoire of survival behaviors regulated by LH circuits.
format	article
author	Justin N. Siemian Cara B. Borja Sarah Sarsfield Alexandre Kisner Yeka Aponte
author_facet	Justin N. Siemian Cara B. Borja Sarah Sarsfield Alexandre Kisner Yeka Aponte
author_sort	Justin N. Siemian
title	Lateral hypothalamic fast-spiking parvalbumin neurons modulate nociception through connections in the periaqueductal gray area
title_short	Lateral hypothalamic fast-spiking parvalbumin neurons modulate nociception through connections in the periaqueductal gray area
title_full	Lateral hypothalamic fast-spiking parvalbumin neurons modulate nociception through connections in the periaqueductal gray area
title_fullStr	Lateral hypothalamic fast-spiking parvalbumin neurons modulate nociception through connections in the periaqueductal gray area
title_full_unstemmed	Lateral hypothalamic fast-spiking parvalbumin neurons modulate nociception through connections in the periaqueductal gray area
title_sort	lateral hypothalamic fast-spiking parvalbumin neurons modulate nociception through connections in the periaqueductal gray area
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/d0a594f60e23400196e7204bf33e03e1
work_keys_str_mv	AT justinnsiemian lateralhypothalamicfastspikingparvalbuminneuronsmodulatenociceptionthroughconnectionsintheperiaqueductalgrayarea AT carabborja lateralhypothalamicfastspikingparvalbuminneuronsmodulatenociceptionthroughconnectionsintheperiaqueductalgrayarea AT sarahsarsfield lateralhypothalamicfastspikingparvalbuminneuronsmodulatenociceptionthroughconnectionsintheperiaqueductalgrayarea AT alexandrekisner lateralhypothalamicfastspikingparvalbuminneuronsmodulatenociceptionthroughconnectionsintheperiaqueductalgrayarea AT yekaaponte lateralhypothalamicfastspikingparvalbuminneuronsmodulatenociceptionthroughconnectionsintheperiaqueductalgrayarea
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Lateral hypothalamic fast-spiking parvalbumin neurons modulate nociception through connections in the periaqueductal gray area

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