Deep brain stimulation improves behavior and modulates neural circuits in a rodent model of schizophrenia

Lior Bikovsky, Ravit Hadar, María Luisa Soto-Montenegro, Julia Klein, Ina Weiner, Manuel Desco, Javier Pascau, Christine Winter*, Clement Hamani

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Schizophrenia is a debilitating psychiatric disorder with a significant number of patients not adequately responding to treatment. Deep brain stimulation (DBS) is a surgical technique currently investigated for medically-refractory psychiatric disorders. Here, we use the poly I:C rat model of schizophrenia to study the effects of medial prefrontal cortex (mPFC) and nucleus accumbens (Nacc) DBS on two behavioral schizophrenia-like deficits, i.e. sensorimotor gating, as reflected by disrupted prepulse inhibition (PPI), and attentional selectivity, as reflected by disrupted latent inhibition (LI). In addition, the neurocircuitry influenced by DBS was studied using FDG PET. We found that mPFC- and Nacc-DBS alleviated PPI and LI abnormalities in poly I:C offspring, whereas Nacc- but not mPFC-DBS disrupted PPI and LI in saline offspring. In saline offspring, mPFC-DBS increased metabolism in the parietal cortex, striatum, ventral hippocampus and Nacc, while reducing it in the brainstem, cerebellum, hypothalamus and periaqueductal gray. Nacc-DBS, on the other hand, increased activity in the ventral hippocampus and olfactory bulb and reduced it in the septal area, brainstem, periaqueductal gray and hypothalamus. In poly I:C offspring changes in metabolism following mPFC-DBS were similar to those recorded in saline offspring, except for a reduced activity in the brainstem and hypothalamus. In contrast, Nacc-DBS did not induce any statistical changes in brain metabolism in poly I:C offspring. Our study shows that mPFC- or Nacc-DBS delivered to the adult progeny of poly I:C treated dams improves deficits in PPI and LI. Despite common behavioral responses, stimulation in the two targets induced different metabolic effects.

Original languageEnglish
Pages (from-to)142-150
Number of pages9
JournalExperimental Neurology
Volume283
DOIs
StatePublished - 1 Sep 2016

Funding

FundersFunder number
EraNet Neuron framework
Fundación Mapfre and Comunidad de MadridS2013/ICE-2958
Ministry of Economy and Competitiveness ISCIII-FISCPII14/00005, FIS PI14/00860
Canadian Institutes of Health ResearchFRN 110068
European Commission
Deutsche ForschungsgemeinschaftPAK 591 (WI 2140/2-1
Bundesministerium für Bildung und Forschung01EW1103
Ministry of Health, State of Israel3-8580
European Regional Development Fund

    Keywords

    • Deep brain stimulation
    • FDG-PET
    • Latent inhibition
    • Maternal immune activation rat model
    • Prepulse inhibition
    • Schizophrenia

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