Functional Dysregulations in CA1 Hippocampal Networks of a 3-Hit Mouse Model of Schizophrenia

Autor: Jean-Marie Billard, Solenn Percelay, Valentine Bouet, Michel Boulouard, Thomas Freret, Annie Andrieux
Přispěvatelé: Mobilités : Vieillissement, Pathologie, Santé (COMETE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Psychosis
hippocampus
Long-Term Potentiation
Hippocampus
Biology
Neurotransmission
Hippocampal formation
Synaptic Transmission
Article
Catalysis
psychiatric disorder
lcsh:Chemistry
Inorganic Chemistry
Mice
03 medical and health sciences
0302 clinical medicine
medicine
Animals
Humans
Theta Rhythm
Physical and Theoretical Chemistry
long term potentiation
lcsh:QH301-705.5
CA1 Region
Hippocampal
Molecular Biology
Spectroscopy
functional plasticity
GABAA receptor
Organic Chemistry
Long-term potentiation
General Medicine
NMDA receptor
medicine.disease
Mice
Mutant Strains
Computer Science Applications
Disease Models
Animal
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Schizophrenia
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Neuroscience
030217 neurology & neurosurgery
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, MDPI, 2021, 22 (5), pp.2644. ⟨10.3390/ijms22052644⟩
International Journal of Molecular Sciences, Vol 22, Iss 2644, p 2644 (2021)
Volume 22
Issue 5
ISSN: 1661-6596
1422-0067
Popis: International audience; For a better translation from treatment designs of schizophrenia to clinical efficiency, there is a crucial need to refine preclinical animal models. In order to consider the multifactorial nature of the disorder, a new mouse model associating three factors (genetic susceptibility—partial deletion of the MAP6 gene, early-life stress—maternal separation, and pharmacological treatment—chronic Δ-9-tetrahydrocannabinol during adolescence) has recently been described. While this model depicts a schizophrenia-like phenotype, the neurobiological correlates remain unknown. Synaptic transmission and functional plasticity of the CA1 hippocampal region of male and female 3-hit mice were therefore investigated using electrophysiological recordings on the hippocampus slice. While basal excitatory transmission remained unaffected, NMDA receptor (NMDAr)-mediated long-term potentiation (LTP) triggered by theta-burst (TBS) but not by high-frequency (HFS) stimulation was impaired in 3-hit mice. Isolated NMDAr activation was not affected or even increased in female 3-hit mice, revealing a sexual dimorphism. Considering that the regulation of LTP is more prone to inhibitory tone if triggered by TBS than by HFS, the weaker potentiation in 3-hit mice suggests a deficiency of intrinsic GABA regulatory mechanisms. Indeed, NMDAr activation was increased by GABAA receptor blockade in wild-type but not in 3-hit mice. This electrophysiological study highlights dysregulations of functional properties and plasticity in hippocampal networks of 3-hit mice, one of the mechanisms suspected to contribute to the pathophysiology of schizophrenia. It also shows differences between males and females, supporting the sexual dimorphism observed in the disorder. Combined with the previously reported study, the present data reinforce the face validity of the 3-hit model that will help to consider new therapeutic strategies for psychosis.
Databáze: OpenAIRE
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