Modulation of forebrain function by nucleus incertus and relaxin-3/RXFP3 signaling

Francisco E. Olucha-Bordonau, Héctor Albert-Gascó, Francisco Ros-Bernal, Valeria Rytova, Emma K.E. Ong-Pålsson, Sherie Ma, Ana M. Sánchez-Pérez, Andrew L. Gundlach

Research output: Contribution to journalReview ArticleResearchpeer-review

Abstract

The nucleus incertus (NI) in the pontine tegmentum sends ascending projections to the midbrain, hypothalamus, amygdala, basal forebrain, hippocampus, and prefrontal cortex, and has a postulated role in modulating several forebrain functions. A substantial population of GABAergic NI neurons expresses the neuropeptide, relaxin-3, which acts via the Gi/o-protein-coupled receptor, RXFP3, present throughout the forebrain target regions. Broad and specific manipulations of these systems by activation or inhibition of the NI or modulating RXFP3 signaling have revealed key insights into the likely influence of the NI/relaxin-3/RXFP3 system on modalities including arousal, feeding, stress responses, anxiety and addiction, and attention and memory. This range of actions corresponds to a likely impact of NI/(relaxin-3) projections on multiple integrated circuits, but makes it difficult to draw conclusions about a generalized function for this network. This review will focus on the key physiological process of oscillatory theta rhythm and the neural circuits that promote it during behavioral activation, highlighting the ability of NI and relaxin-3/RXFP3 signaling systems to modulate these circuits. A better understanding of these mechanisms may provide a way to therapeutically adjust malfunction of forebrain activity present in several pathological conditions.

Original languageEnglish
Pages (from-to)694-702
Number of pages9
JournalCNS Neuroscience and Therapeutics
Volume24
Issue number8
DOIs
Publication statusPublished - Aug 2018
Externally publishedYes

Keywords

  • Arousal
  • Brainstem
  • Feeding
  • GABA
  • Hippocampus
  • Septum
  • Social interaction
  • Theta rhythm

Cite this

Olucha-Bordonau, F. E., Albert-Gascó, H., Ros-Bernal, F., Rytova, V., Ong-Pålsson, E. K. E., Ma, S., ... Gundlach, A. L. (2018). Modulation of forebrain function by nucleus incertus and relaxin-3/RXFP3 signaling. CNS Neuroscience and Therapeutics, 24(8), 694-702. https://doi.org/10.1111/cns.12862
Olucha-Bordonau, Francisco E. ; Albert-Gascó, Héctor ; Ros-Bernal, Francisco ; Rytova, Valeria ; Ong-Pålsson, Emma K.E. ; Ma, Sherie ; Sánchez-Pérez, Ana M. ; Gundlach, Andrew L. / Modulation of forebrain function by nucleus incertus and relaxin-3/RXFP3 signaling. In: CNS Neuroscience and Therapeutics. 2018 ; Vol. 24, No. 8. pp. 694-702.
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Olucha-Bordonau, FE, Albert-Gascó, H, Ros-Bernal, F, Rytova, V, Ong-Pålsson, EKE, Ma, S, Sánchez-Pérez, AM & Gundlach, AL 2018, 'Modulation of forebrain function by nucleus incertus and relaxin-3/RXFP3 signaling', CNS Neuroscience and Therapeutics, vol. 24, no. 8, pp. 694-702. https://doi.org/10.1111/cns.12862

Modulation of forebrain function by nucleus incertus and relaxin-3/RXFP3 signaling. / Olucha-Bordonau, Francisco E.; Albert-Gascó, Héctor; Ros-Bernal, Francisco; Rytova, Valeria; Ong-Pålsson, Emma K.E.; Ma, Sherie; Sánchez-Pérez, Ana M.; Gundlach, Andrew L.

In: CNS Neuroscience and Therapeutics, Vol. 24, No. 8, 08.2018, p. 694-702.

Research output: Contribution to journalReview ArticleResearchpeer-review

TY - JOUR

T1 - Modulation of forebrain function by nucleus incertus and relaxin-3/RXFP3 signaling

AU - Olucha-Bordonau, Francisco E.

AU - Albert-Gascó, Héctor

AU - Ros-Bernal, Francisco

AU - Rytova, Valeria

AU - Ong-Pålsson, Emma K.E.

AU - Ma, Sherie

AU - Sánchez-Pérez, Ana M.

AU - Gundlach, Andrew L.

PY - 2018/8

Y1 - 2018/8

N2 - The nucleus incertus (NI) in the pontine tegmentum sends ascending projections to the midbrain, hypothalamus, amygdala, basal forebrain, hippocampus, and prefrontal cortex, and has a postulated role in modulating several forebrain functions. A substantial population of GABAergic NI neurons expresses the neuropeptide, relaxin-3, which acts via the Gi/o-protein-coupled receptor, RXFP3, present throughout the forebrain target regions. Broad and specific manipulations of these systems by activation or inhibition of the NI or modulating RXFP3 signaling have revealed key insights into the likely influence of the NI/relaxin-3/RXFP3 system on modalities including arousal, feeding, stress responses, anxiety and addiction, and attention and memory. This range of actions corresponds to a likely impact of NI/(relaxin-3) projections on multiple integrated circuits, but makes it difficult to draw conclusions about a generalized function for this network. This review will focus on the key physiological process of oscillatory theta rhythm and the neural circuits that promote it during behavioral activation, highlighting the ability of NI and relaxin-3/RXFP3 signaling systems to modulate these circuits. A better understanding of these mechanisms may provide a way to therapeutically adjust malfunction of forebrain activity present in several pathological conditions.

AB - The nucleus incertus (NI) in the pontine tegmentum sends ascending projections to the midbrain, hypothalamus, amygdala, basal forebrain, hippocampus, and prefrontal cortex, and has a postulated role in modulating several forebrain functions. A substantial population of GABAergic NI neurons expresses the neuropeptide, relaxin-3, which acts via the Gi/o-protein-coupled receptor, RXFP3, present throughout the forebrain target regions. Broad and specific manipulations of these systems by activation or inhibition of the NI or modulating RXFP3 signaling have revealed key insights into the likely influence of the NI/relaxin-3/RXFP3 system on modalities including arousal, feeding, stress responses, anxiety and addiction, and attention and memory. This range of actions corresponds to a likely impact of NI/(relaxin-3) projections on multiple integrated circuits, but makes it difficult to draw conclusions about a generalized function for this network. This review will focus on the key physiological process of oscillatory theta rhythm and the neural circuits that promote it during behavioral activation, highlighting the ability of NI and relaxin-3/RXFP3 signaling systems to modulate these circuits. A better understanding of these mechanisms may provide a way to therapeutically adjust malfunction of forebrain activity present in several pathological conditions.

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KW - Brainstem

KW - Feeding

KW - GABA

KW - Hippocampus

KW - Septum

KW - Social interaction

KW - Theta rhythm

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U2 - 10.1111/cns.12862

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Olucha-Bordonau FE, Albert-Gascó H, Ros-Bernal F, Rytova V, Ong-Pålsson EKE, Ma S et al. Modulation of forebrain function by nucleus incertus and relaxin-3/RXFP3 signaling. CNS Neuroscience and Therapeutics. 2018 Aug;24(8):694-702. https://doi.org/10.1111/cns.12862