Schizophrenia-like reduced sensorimotor gating in intact inbred and outbred rats is associated with decreased medial prefrontal cortex activity and volume
Tapias-Espinosa, Carles (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Río-Álamos, Cristobal (Universidad Austral de Chile. Departamento de Psicologia)
Sánchez González, Ana (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Oliveras, Ignasi (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Sampedro-Viana, Daniel (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Castillo-Ruiz, Mª del Mar (Universitat Autònoma de Barcelona. Institut de Neurociències)
Cañete, Toni (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Tobeña, Adolf 1950- (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Fernández-Teruel, Alberto (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)

Date:	2019
Abstract:	Prepulse inhibition (PPI) of startle response is a measure of sensorimotor gating that is impaired in schizophrenia and in many other clinical conditions. Rat models using pharmacological or surgical strategies reveal that PPI is modulated by the cortico-striatal-pallido-thalamic (CSPT) circuit. Here, we explore whether spontaneous variation in PPI in intact inbred and outbred rats is associated with functional and structural differences in the CSPT circuit. Inbred Roman High-(RHA) and Low-avoidance (RLA) and outbred heterogeneous stock (HS) rats were assessed for PPI, brain activity, and brain volume. Brain activity was assessed by c-Fos expression and brain volume by magnetic resonance imaging. Relevant structures of the CSPT circuit were evaluated, such as the medial prefrontal cortex (mPFC), cingulate cortex, hippocampus (HPC), amygdala, nucleus accumbens (NAc), and dorsal striatum. RHA showed lower PPI than RLA rats, while HS rats were stratified by their PPI levels in three groups. Reduced PPI was accompanied by decreased mPFC activity in Roman and HS rats and increased NAc shell activity in HS rats. Low PPI was also associated with decreased mPFC and HPC volumes in Roman and HS rats. This study reports a consistent relationship between decreased function and volume of the mPFC and spontaneous low-PPI levels in inbred and outbred intact rats. Moreover, our findings suggest that, apart from a hypoactive and smaller mPFC, a hyperactive NAc and smaller HPC may underlie reduced PPI levels. Our results support the notion that sensorimotor gating is modulated by forebrain structures and highlight the importance of the mPFC in its regulation.
Grants:	Agencia Estatal de Investigación PSI2017-82257-P Agència de Gestió d'Ajuts Universitaris i de Recerca 2017SGR-1586 Ministerio de Educación, Cultura y Deporte FPU15/06307
Rights:	Tots els drets reservats.
Language:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Subject:	Dopamine-glutamate interactions ; Excitotoxic lesions ; Latent inhibition ; Neural circuits ; Nucleus-accumbens ; Prepulse inhibition ; Roman high-avoidance ; Startle reflex ; Strain differences ; Ventral hippocampus
Published in:	Neuropsychopharmacology, Vol. 44 Núm. 11 (2019) , p. 1975-1984, ISSN 1740-634X Neuropsychopharmacology, 2019 , ISSN 1740-634X

DOI: 10.1038/s41386-019-0392-x
PMID: 30986819

36 p, 1.6 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles