title: Altered cortico-striatal crosstalk underlies object recognition memory deficits in the sub-chronic phencyclidine model of schizophrenia.
abstract: The neural mechanisms underlying cognitive deficits in schizophrenia are poorly understood. Sub-chronic treatment with the NMDA antagonist phencyclidine (PCP) produces cognitive abnormalities in rodents that reliably model aspects of the neurocognitive alterations observed in schizophrenia. Given that network activity across regions encompassing medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) plays a significant role in motivational and cognitive tasks, we measured activity across cortico-striatal pathways in PCP-treated rats to characterize neural enabling and encoding of task performance in a novel object recognition task. We found that PCP treatment impaired task performance and concurrently (1) reduced tonic NAc neuronal activity, (2) desynchronized cross-activation of mPFC and NAc neurons, and (3) prevented the increase in mPFC and NAc neural activity associated with the exploration of a novel object in relation to a familiar object. Taken together, these observations reveal key neuronal and network-level adaptations underlying PCP-induced cognitive deficits, which may contribute to the emergence of cognitive abnormalities in schizophrenia.
authors.affiliation: Department of Neuroscience, Psychology and Behaviour, University of Leicester, Leicester, LE1 9HN, UK.
authors.forename: Aman
authors.initials: A
authors.lastname: Asif-Malik
authors.affiliation: Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, NJ, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Dautan
authors.affiliation: Department of Neuroscience, Psychology and Behaviour, University of Leicester, Leicester, LE1 9HN, UK.
authors.forename: Andrew M J
authors.initials: AMJ
authors.lastname: Young
authors.affiliation: Department of Neuroscience, Psychology and Behaviour, University of Leicester, Leicester, LE1 9HN, UK. tvg3@le.ac.uk.
authors.forename: Todor V
authors.initials: TV
authors.lastname: Gerdjikov
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006213:Hallucinogens / Q000633:toxicity; D008569:Memory Disorders / Q000209:etiology* / Q000473:pathology*; D009434:Neural Pathways / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000473:pathology / Q000503:physiopathology*; D010622:Phencyclidine / Q000633:toxicity; D017397:Prefrontal Cortex / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology*; D012559:Schizophrenia / Q000139:chemically induced / Q000150:complications*
chemical_list: D006213:Hallucinogens; D010622:Phencyclidine
keywords: Medial prefrontal cortex; Neurophysiology; Novel object recognition; Nucleus accumbens; Phencyclidine; Schizophrenia