cortex

Project number:

201

Project title:

Metaplasticity underlying cognitive impairments in the hippocampus in epilepsy

Project supervisor:

Project description:

Synaptic plasticity in the form of long-term potentiation (LTP) and long-term depression (LTD) underlies declarative memory processing in the hippocampus. A disruption of synaptic plasticity may comprise a key component of brain diseases that involve cognitive impairments. This may take the form of metaplasticity- an alteration of synaptic responsiveness that arises due to prior synaptic experience, that can profoundly alter the ability of a synapse to express subsequently induced synaptic plasticity.

In this project we will investigate whether seizure activity, typical of temporal lobe epilepsy and physiological synaptic activity generates metaplasticity in the rat hippocampus, whether this activity alters the direction of change of synaptic strength and whether this affects cognitive ability in rats. The role of the glutamatergic system, and in particular the metabotropic glutamate receptor, will be investigated with regard to this phenomenon. In addition we will examine whether metabotropic glutamate receptors (mGluRs) can be targeted as a possible therapeutic strategy in addressing cognitive impairments in epilepsy. In vivo electrophysiology of the rat hippocampus coupled with behavioural analysis of learning will be implemented. Rat models of temporal lobe epilepsy (kindling, pilocarpine) will be investigated.

Possible cortex partners for rotation:

In cooperation with the Oslo partners (O.P. Ottersen), investigations into the role of glutamate receptors in the hippocampal pathology of epilepsy could be investigated. It is likely that the distribution and complement of mGluRs is altered following induction of a chronic epileptic state. An electron microscopy study to examine hippocampal distribution of mGluRs following epilepsy and synaptic plasticity will be conducted.

In cooperation with the Berlin partners (U.Heinemann), investigations into the role of metabotropic glutamate receptors in epilepsy in human hippocampi will be studied. Here a bridge between basic research using animal models and clinical research will be forged.