Document type
Journal articles
Document subtype
Full paper
Title
Mismatch novelty exploration training shifts VPAC1 receptor-mediated modulation of hippocampal synaptic plasticity by endogenous VIP in male rats
Participants in the publication
F Aidil-Carvalho (Author)
INSTITUTO DE MEDICINA MOLECULAR DA UL
A Caulino-Rocha (Author)
BioISI - Biosystems & Integrative Sciences Institute
Unidade de I&D e Inovação
CQB
JA Ribeiro (Author)
FACULDADE DE MEDICINA DA UL
INSTITUTO DE MEDICINA MOLECULAR DA UL
D Cunha-Reis (Author)
Dep. Biologia Vegetal
BioISI
Summary
Novelty influences hippocampal-dependent memory through metaplasticity. Mismatch novelty detection activates the human hippocampal CA1 area and enhances rat hippocampal-dependent learning and exploration. Remarkably, mismatch novelty training (NT) also enhances rodent hippocampal synaptic plasticity while inhibition of VIP interneurons promotes rodent exploration. Since VIP, acting on VPAC1 receptors (Rs), restrains hippocampal LTP and depotentiation by modulating disinhibition, we now investigated the impact of NT on VPAC1 modulation of hippocampal synaptic plasticity in male Wistar rats. NT enhanced both CA1 hippocampal LTP and depotentiation unlike exploring an empty holeboard (HT) or a fixed configuration of objects (FT). Blocking VIP VPAC1Rs with PG 97269 (100 nM) enhanced both LTP and depotentiation in naïve animals, but this effect was less effective in NT rats. Altered endogenous VIP modulation of LTP was absent in animals exposed to the empty environment (HT). HT and FT animals showed mildly enhanced synaptic VPAC1R levels, but neither VIP nor VPAC1R levels were altered in NT animals. Conversely, NT enhanced the GluA1/GluA2 AMPAR ratio and gephyrin synaptic content but not PSD-95 excitatory synaptic marker. In conclusion, NT influences hippocampal synaptic plasticity by reshaping brain circuits modulating disinhibition and its control by VIP-expressing hippocampal interneurons while upregulation of VIP VPAC1Rs is associated with the maintenance of VIP control of LTP in FT and HT animals. This suggests VIP receptor ligands may be relevant to co-adjuvate cognitive recovery therapies in aging or epilepsy, where LTP/LTD imbalance occurs.
Date of Publication
2024-04-24
Institution
FACULDADE DE CIÊNCIAS DA UNIVERSIDADE DE LISBOA
Where published
Journal of Neuroscience Research
Publication Identifiers
Publisher
Wiley
Number of pages
16
Starting page
1
Last page
16
Document Identifiers
DOI -
https://doi.org/10.1002/jnr.25333
Rankings
CITESCORE (2020 onward) Q1 (2022) - 8.2 - Cellular and Molecular Neuroscience
Web Of Science Q2 (2022) - 4.2 - Neuroscience
SCIMAGO Q2 (2023) - 1.258 - Cellular and Molecular Neuroscience
Keywords
mismatch novelty
VIP
synaptic plasticity
hippocampus