Investigating brain network deficits in a rodent schizophrenia model

Lead Research Organisation: University of Leicester
Department Name: Neuroscience, Psychology and Behaviour

Abstract

Schizophrenia is a chronic disorder characterized by positive symptoms, negative symptoms, and cognitive impairment (van Os and Kapur, 2009). A wide range of cognitive impairments have been associated with schizophrenia, including deficits in attention, speed of processing, learning and memory, problem solving, and executive functioning. Cognitive function is strongly associated with functional outcome in patients (Domingo et al., 2015; Green and Harvey, 2014; Fett et al., 2011) but the pathophysiology of cognitive impairment in schizophrenia remains largely unclear (Green and Harvey, 2014). Furthermore, antipsychotic medication used to treat schizophrenia have minimal effects on cognition (Keefe et al., 2007). This project will determine neurophysiological and behavioural deficits in a preclinical mouse model of schizophrenia using in vivo techniques. Previous studies have identified the role of altered potassium (K+) channels involved in the cortical manifestations of schizophrenia. Therefore, to further understand the physiological role of K+ channels in neural deficits associated with schizophrenia, transgenic mice will be used to characterize the role of these channels in corticolimbic network activity. Dense multi-region recordings from large populations of neurons using silicon probes will be carried out in awake mice from target regions implicated in schizophrenia in humans and other rodent models. Behavioural and neural population activity recorded simultaneously will be subjected to computational analyses to investigate brain network deficits. We will also assess how neural activity in the target regions is modulated by current and/or candidate antipsychotics in awake mice, potentially identifying a novel antipsychotic treatments. To assess how the physiology of this system is modulated during cognition, population spike activity recorded during cognitive tasks in behaving animals.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M01116X/1 01/10/2015 30/09/2023
2098611 Studentship BB/M01116X/1 01/10/2018 30/09/2022 Emma Condon