Intrinsic cellular mechanisms of memory
In learning and memory it has recently become clear that in addition
to synaptic plasticity there are cellular changes in excitability due
to changes in ion channels. The project focuses on cationic (TRP)
currents which are known from in vitro studies to produce long-lasting
depolarizing plateau potentials. Further, these currents are activated
by group I metabotropic glutamate receptors as well as muscarinic type
1 receptors, and blocking of these receptors have been shown to
produce behavioral deficits in long-term and working memory
experiments. In the project, we combine pharmacological,
electrophysiological and modeling techniques.
Reducing epileptogenic activity using novel dendritic potassium channels.
Synchronous activity is an integral part of brain function. At the
single neuron level, there may under normal conditions be mechanisms
that maximizes processing while proving sufficient safety margins to
undesirable hypersynchronous states such as epilepsy. In this
project using quantitative modeling we are studying the possibility of
controlling a neurons bias to respond to synchronous synaptic input by
adding a novel potassium current. Experimentally, pharmacological
manipulation of endogenous ion channel types, or genetic knock-in of
new channels, might provide possible ways of implementing our results.
Biomolecular target design using computational search strategies
In this project, we develop a computational search method to design
ion channels so that they can achieve optimal
physiological/terapeutical effect on cell or network function. The
project currently evaluates direct search strategies to find optimal
characteristics. In each cycle of the procedure, new channel
parameters are set, next biophysical simulations include the channel
in the cells of the network/system at study. From the simulations,
resulting physiological function is measured/evaluated. Based on this
evaluation, new parameters are computed using the search method.