Project Title:

Exploration of new drug targets in neuropsychiatric disorders – focus on excitatory /inhibitory imbalance

Yasmine Iacone

Objectives:

Imbalance in excitatory and inhibitory activity (E/I imbalance) has been linked to the pathophysiology underlying several neuropsychiatric disorders, such as epilepsy and schizophrenia. Genetic studies have linked Hyperpolarization-activated cyclic nucleotide–gated (HCN) channels to both of these disorders. Furthermore, improper trafficking of the channels to the neuronal cell surface has been linked to depression, overall making it an attractive drug target. HCN channels are believed to have multiple functions on neuronal activity and are expressed in both excitatory and inhibitory neurons with different subcellular localization. In the present project, we aim at elucidating the role of HCN channels in changed E/I balance. We will address this by characterizing how HCN expression in individual cell types, subcellular localization and expression levels affect single cell excitability as well as the overall neuronal network activity.

Methodology:

A combination of cell biology techniques with electrophysiological recordings in neuronal cultures and brain slice from both wild type animals and animal models (genetic and/or developmental) of schizophrenia/epilepsy/depression.

Morten Skøtt Thomsen Lindskov