Relaxin-3 inputs target hippocampal interneurons and deletion of hilar relaxin-3 receptors in "floxed-RXFP3" mice impairs spatial memory
- PMID: 28100033
- DOI: 10.1002/hipo.22709
Relaxin-3 inputs target hippocampal interneurons and deletion of hilar relaxin-3 receptors in "floxed-RXFP3" mice impairs spatial memory
Abstract
Hippocampus is innervated by γ-aminobutyric acid (GABA) "projection" neurons of the nucleus incertus (NI), including a population expressing the neuropeptide, relaxin-3 (RLN3). In studies aimed at gaining an understanding of the role of RLN3 signaling in hippocampus via its Gi/o -protein-coupled receptor, RXFP3, we examined the distribution of RLN3-immunoreactive nerve fibres and RXFP3 mRNA-positive neurons in relation to hippocampal GABA neuron populations. RLN3-positive elements were detected in close-apposition with a substantial population of somatostatin (SST)- and GABA-immunoreactive neurons, and a smaller population of parvalbumin- and calretinin-immunoreactive neurons in different hippocampal areas, consistent with the relative distribution patterns of RXFP3 mRNA and these marker transcripts. In light of the functional importance of the dentate gyrus (DG) hilus in learning and memory, and our anatomical data, we examined the possible influence of RLN3/RXFP3 signaling in this region on spatial memory. Using viral-based Cre/LoxP recombination methods and adult mice with a floxed Rxfp3 gene, we deleted Rxfp3 from DG hilar neurons and assessed spatial memory performance and affective behaviors. Following infusions of an AAV(1/2) -Cre-IRES-eGFP vector, Cre expression was observed in DG hilar neurons, including SST-positive cells, and in situ hybridization histochemistry for RXFP3 mRNA confirmed receptor depletion relative to levels in floxed-RXFP3 mice infused with an AAV(1/2) -eGFP (control) vector. RXFP3 depletion within the DG hilus impaired spatial reference memory in an appetitive T-maze task reflected by a reduced percentage of correct choices and increased time to meet criteria, relative to control. In a continuous spontaneous alternation Y-maze task, RXFP3-depleted mice made fewer alternations in the first minute, suggesting impairment of spatial working memory. However, RXFP3-depleted and control mice displayed similar locomotor activity, anxiety-like behavior in light/dark box and elevated-plus maze tests, and learning and long-term memory retention in the Morris water maze. These data indicate endogenous RLN3/RXFP3 signaling can modulate hippocampal-dependent spatial reference and working memory via effects on SST interneurons, and further our knowledge of hippocampal cognitive processing. © 2017 Wiley Periodicals, Inc.
Keywords: Cre/LoxP; GABA/somatostatin interneurons; RXFP3; dentate gyrus; nucleus incertus.
© 2017 Wiley Periodicals, Inc.
Similar articles
-
Septal GABA and Glutamate Neurons Express RXFP3 mRNA and Depletion of Septal RXFP3 Impaired Spatial Search Strategy and Long-Term Reference Memory in Adult Mice.Front Neuroanat. 2019 Mar 8;13:30. doi: 10.3389/fnana.2019.00030. eCollection 2019. Front Neuroanat. 2019. PMID: 30906254 Free PMC article.
-
Chronic activation of the relaxin-3 receptor on GABA neurons in rat ventral hippocampus promotes anxiety and social avoidance.Hippocampus. 2019 Oct;29(10):905-920. doi: 10.1002/hipo.23089. Epub 2019 Mar 19. Hippocampus. 2019. PMID: 30891856
-
Distribution of relaxin-3 and RXFP3 within arousal, stress, affective, and cognitive circuits of mouse brain.J Comp Neurol. 2010 Oct 1;518(19):4016-45. doi: 10.1002/cne.22442. J Comp Neurol. 2010. PMID: 20737598
-
Modulation of forebrain function by nucleus incertus and relaxin-3/RXFP3 signaling.CNS Neurosci Ther. 2018 Aug;24(8):694-702. doi: 10.1111/cns.12862. Epub 2018 May 2. CNS Neurosci Ther. 2018. PMID: 29722152 Free PMC article. Review.
-
[A new agent in the mechanisms underlying addiction and ingestion of alcohol: the nucleus incertus and the neuropeptide relaxin-3].Rev Neurol. 2018 Sep 1;67(5):175-186. Rev Neurol. 2018. PMID: 30047120 Review. Spanish.
Cited by
-
Fear memory recall involves hippocampal somatostatin interneurons.PLoS Biol. 2023 Jun 8;21(6):e3002154. doi: 10.1371/journal.pbio.3002154. eCollection 2023 Jun. PLoS Biol. 2023. PMID: 37289847 Free PMC article.
-
Nucleus incertus projections to rat medial septum and entorhinal cortex: rare collateralization and septal-gating of temporal lobe theta rhythm activity.Brain Struct Funct. 2023 Jun;228(5):1307-1328. doi: 10.1007/s00429-023-02650-x. Epub 2023 May 12. Brain Struct Funct. 2023. PMID: 37173580 Free PMC article.
-
The Relaxin-3 Receptor, RXFP3, Is a Modulator of Aging-Related Disease.Int J Mol Sci. 2022 Apr 15;23(8):4387. doi: 10.3390/ijms23084387. Int J Mol Sci. 2022. PMID: 35457203 Free PMC article. Review.
-
Functional Neuroanatomy of the Rat Nucleus Incertus-Medial Septum Tract: Implications for the Cell-Specific Control of the Septohippocampal Pathway.Front Cell Neurosci. 2022 Feb 25;16:836116. doi: 10.3389/fncel.2022.836116. eCollection 2022. Front Cell Neurosci. 2022. PMID: 35281300 Free PMC article.
-
Bidirectional Communication between the Pontine Nucleus Incertus and the Medial Septum Is Carried Out by Electrophysiologically-Distinct Neuronal Populations.J Neurosci. 2022 Mar 16;42(11):2234-2252. doi: 10.1523/JNEUROSCI.0230-21.2022. Epub 2022 Jan 25. J Neurosci. 2022. PMID: 35078925 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases