Cholinergic modulation of grid cell activity in the entorhinal cortex of mice

• Applicant: Dr. Holger Dannenberg
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: from 2016 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 322014644

Episodic memory function in humans and spatial memory function in rodents depend on dynamic cholinergic signaling with high levels of the neuromodulator acetylcholine during the encoding of novel information. However, the mechanisms by which acetylcholine changes cognitive information processing to support the encoding of spatial information are poorly understood. Grid cells of the medial entorhinal cortex exhibit a spatially periodic firing pattern that may reflect the output of a path integration system and has been hypothesized to provide a framework for episodic and spatial memory. I therefore hypothesize that grid cell firing characteristics are modulated by acetylcholine. To test this hypothesis, I will use tetrode recordings of entorhinal grid cell activity as well as the local field potentials in freely exploring mice combined with optogenetic silencing of cholinergic neurons in the medial septum/diagonal band of Broca, the major source of acetylcholine in the entorhinal cortex. The results of this study will enable us with the unique opportunity to understand the link between the cholinergic system and grid cell activity. In addition, these results may explain the correlation between memory disorders and the deficits in cholinergic signaling observed in Alzheimer's disease patients.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Michael Hasselmo, Ph.D.