Different populations of prostaglandin EP3 receptor-expressing preoptic neurons project to two fever-mediating sympathoexcitatory brain regions

Y. Nakamura, K. Nakamura, Shaun Morrison

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

The central mechanism of fever induction is triggered by an action of prostaglandin E2 (PGE2) on neurons in the preoptic area (POA) through the EP3 subtype of prostaglandin E receptor. EP3 receptor (EP3R)-expressing POA neurons project directly to the dorsomedial hypothalamus (DMH) and to the rostral raphe pallidus nucleus (rRPa), key sites for the control of thermoregulatory effectors. Based on physiological findings, we hypothesize that the febrile responses in brown adipose tissue (BAT) and those in cutaneous vasoconstrictors are controlled independently by separate neuronal pathways: PGE2 pyrogenic signaling is transmitted from EP3R-expressing POA neurons via a projection to the DMH to activate BAT thermogenesis and via another projection to the rRPa to increase cutaneous vasoconstriction. In this case, DMH-projecting and rRPa-projecting neurons would constitute segregated populations within the EP3R-expressing neuronal group in the POA. Here, we sought direct anatomical evidence to test this hypothesis with a double-tracing experiment in which two types of the retrograde tracer, cholera toxin b-subunit (CTb), conjugated with different fluorophores were injected into the DMH and the rRPa of rats and the resulting retrogradely labeled populations of EP3R-immunoreactive neurons in the POA were identified with confocal microscopy. We found substantial numbers of EP3R-immunoreactive neurons in both the DMH-projecting and the rRPa-projecting populations. However, very few EP3R-immunoreactive POA neurons were labeled with both the CTb from the DMH and that from the rRPa, although a substantial number of neurons that were not immunoreactive for EP3R were double-labeled with both CTbs. The paucity of the EP3R-expressing neurons that send collaterals to both the DMH and the rRPa suggests that pyrogenic signals are sent independently to these caudal brain regions from the POA and that such pyrogenic outputs from the POA reflect different control mechanisms for BAT thermogenesis and for cutaneous vasoconstriction by distinct sets of POA neurons.

Original languageEnglish (US)
Pages (from-to)614-620
Number of pages7
JournalNeuroscience
Volume161
Issue number2
DOIs
StatePublished - Jun 30 2009

Fingerprint

Prostaglandin Receptors
Preoptic Area
Fever
Neurons
Hypothalamus
Brain
Population
Brown Adipose Tissue
Thermogenesis
Cholera Toxin
Vasoconstriction
Dinoprostone
Skin
Receptors, Prostaglandin E, EP3 Subtype
Vasoconstrictor Agents
Midbrain Raphe Nuclei
Confocal Microscopy

Keywords

  • GABA
  • inflammation
  • rostral medullary raphe
  • stress response
  • sympathetic nervous system
  • thermoregulation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Different populations of prostaglandin EP3 receptor-expressing preoptic neurons project to two fever-mediating sympathoexcitatory brain regions. / Nakamura, Y.; Nakamura, K.; Morrison, Shaun.

In: Neuroscience, Vol. 161, No. 2, 30.06.2009, p. 614-620.

Research output: Contribution to journalArticle

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