Séminaire de Hannah Clarke

Friday June 30, 2023 at 14:30, INT Gastaut meeting room

Hannah Clarke (University of Cambridge)

invited by Eduardo Gascon

Schizophrenia, perineuronal nets, and the marmoset hippocampal-prefrontal pathway

Abstract:

Schizophrenia is typically associated with three main symptom clusters: positive symptoms that are fairly well treated with antipsychotic drugs, and emotional and cognitive disruptions that are harder to treat, and profoundly impact quality of life (Green and Nuechterlein, 2004). Clinical neuroimaging studies and rodent models of schizophrenia have implicated dysfunction in regions of the PFC, and glutamatergic overactivity within the anterior hippocampus (aHipp), in the mechanisms underlying schizophrenia symptoms (Schobel et al., 2013). In addition, disruption of hippocampal parvalbumin-positive inhibitory GABAergic interneurons, and loss of their extracellular matrix support structure, the perineuronal net (PNN), induce schizophrenia-like changes in rodent models (Shah and Lodge, 2013). However, while the role of the aHipp has been considered in the positive symptoms of schizophrenia, the aHipp also projects directly to the PFC, thus aHipp glutamatergic hyperfunction may also induce alterations in PFC function that underlie the cognitive symptoms. These data seek therefore to integrate these findings by combining aHipp PNN degradation, intracerebral manipulations, behavioural analysis, microdialysis and neuroimaging in marmoset monkeys – a species whose PFC is closer to that of humans than rodents. I will provide evidence that aHipp PNN degradation not only alters neurochemistry within the PFC, but also alters behaviours of relevance to both the positive and cognitive symptoms of schizophrenia. These studies demonstrate the importance of primate translational neuroscience for the development of a mechanistic understanding of prefrontal cortex function, with a view to developing new treatments for disorders of major personal and societal consequence.