C04 Global and local inhibition in the normal and epileptic dentate gyrus


The dentate gyrus as a regulated gate

The hippocampal dentate gyrus (DG) is critically involved in both normal and pathological brain function. It is located at the origin of the hippocampal trisynaptic circuit, conveying information from different sensory modalities from the entorhinal cortex to the hippocampus proper. The DG has been proposed to be important in efficiently discriminating similar environments from one another, a process termed ‘pattern separation’. In epilepsy, the DG has been shown to exhibit a high threshold for the generation and propagation of high-frequency activity. Because of this property, it has been viewed as a gate that stringently regulates information transfer to the hippocampus in both the healthy and diseased hippocampus. However, information transfer has to be able to adapt to substantial differences in the richness and type of sensory information. The project will study the role of modulatory neurotransmitters such as acetylcholine and norepinephrine in modulating information transfer in the dentate gyrus. To this end, the project will use two-photon (2P) Ca2+ imaging as well as fiber-based activity measurements and electrophysiology in-vivo in awake animals, combined with opto- and chemogenetics, to find out i) under which conditions and when NE and ACh systems are recruited, and ii) how they affect behaviorally evoked activity in the DG.