Monday 26 Feb 2018: Dynamics Seminar: How do mossy cells influence pattern separation and epilepsy?
Denize Atan - Bristol
LSI Seminar Room A 14:30-15:30
Epilepsy is a severely disabling neurological disorder, and for those with associated cognitive and memory impairments, the psychosocial outcomes are particularly poor. How seizures influence memory is not well understood, but the hippocampus in the temporal lobes is often implicated, because of its fundamental importance to learning and memory and because it is frequently affected by structural abnormalities in epilepsy patients known as hippocampal sclerosis (HS).
Current models of memory storage and recall refer to the hippocampal tri-synaptic circuit, but do not account for the intrinsic circuitry of the dentate gyrus (DG), and its specific role in pattern separation. Pattern separation is the computational rendering of similar inputs into distinct output patterns so that similar memories do not interfere with each other during recall, e.g. the encoding of ‘where I parked my car today’ in a manner distinct from ‘where I parked my car yesterday’. Mossy cells are key components of DG circuitry and are known to die after generalized seizures in mice and humans. Hence, mossy cells provide a mechanism whereby seizures can cause defects in DG circuitry and pattern separation that could explain some of the memory deficits of epilepsy patients.
My group has been working with genetically modified mice that have a specific mossy cell defect in the DG to determine how mossy cells influence pattern separation memory. In this talk, I will describe how we have used molecular techniques, imaging, behavioural paradigms, electrophysiology and computational modelling to investigate the function of this intriguing cell type, and how we have more recently started to translate our findings to patients with epilepsy.