Modification of neural circuits with interneuron transplantation

University Of Vermont & St Agric College, Burlington VT

Investigators

Abstract

PROJECT SUMMARY Temporal lobe epilepsy associated with mesial temporal sclerosis (MTS) is common, frequently difficult to treat medically and therefore many patients have epilepsy surgery. Although temporal lobe resections are often successful at stopping seizures this approach usually fails to improve the commonly identified memory comorbidities and can make those impairments worse. A therapeutic approach in which MTS is modified in a way that reduces epileptic phenomena and leads to an improvement in memory would have a major impact on the quality of life of many patients with MTS. Implantation of interneuron precursors has been shown to reduce seizures and improve cognition. We hypothesize that transplanted interneuron precursors will restore temporal organization of hippocampal pyramidal cells thereby improving abnormalities in rate, temporal and population coding that underpins normal cognitive behavior. In addition they will also minimize hypersynchrony leading to seizure reduction. We propose to study interactions between multiple simultaneously firing hippocampal neurons recorded from CA1 and CA3 bilaterally in awake, freely moving rodents during foraging and during an active place-avoidance task. Systems level changes at the level of rate coding, temporal coding and population coding will be compared between implanted and non-implanted rats. We will use standard and novel analytical tools developed in our laboratories to apply to these data. A detailed systems level understanding of how neural networks need to change in order to improve disease outcomes will guide optimization of cell based therapies and will provide a target for other interventions such as electrical stimulation or optogenetics.