Deep brain stimulation improves behavior and modulates neural circuits in a rodent model of schizophrenia.
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.
School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel.
Lior
L
Bikovsky
Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
Ravit
R
Hadar
Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; CIBERSAM, Madrid, Spain.
María Luisa
ML
Soto-Montenegro
Department of Psychiatry and Psychotherapy, Charité University Medicine Berlin, Campus Charité Mitte, Berlin, Germany.
Julia
J
Klein
School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
Ina
I
Weiner
Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; CIBERSAM, Madrid, Spain; Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Spain.
Manuel
M
Desco
Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; CIBERSAM, Madrid, Spain; Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Spain.
Javier
J
Pascau
Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany. Electronic address: christine.winter@uniklinikum-dresden.de.
Christine
C
Winter
Behavioural Neurobiology Laboratory, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada; Campbell Family Mental Health Research Institute, CAMH, Canada; Division of Neurosurgery, Toronto Western Hospital, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada.
Clement
C
Hamani
D000161:Acoustic Stimulation; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects; D046690:Deep Brain Stimulation; D004195:Disease Models, Animal; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D020233:Gait Disorders, Neurologic / Q000209:etiology*; D007369:Interferon Inducers / Q000633:toxicity; D008297:Male; D001523:Mental Disorders / Q000000981:diagnostic imaging / Q000209:etiology* / Q000628:therapy*; D009714:Nucleus Accumbens / Q000502:physiology; D011070:Poly I-C / Q000633:toxicity; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000502:physiology; D065808:Prepulse Inhibition / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000502:physiology; D012559:Schizophrenia / Q000139:chemically induced / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology*
D007369:Interferon Inducers; D019788:Fluorodeoxyglucose F18; D011070:Poly I-C
Deep brain stimulation; FDG-PET; Latent inhibition; Maternal immune activation rat model; Prepulse inhibition; Schizophrenia