Physiological and pathological activation patterns in the hippocampal dentate gyrus.

• Applicant: Dr. Elisabeth Heynold
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 536202420

The medial temporal lobe with its hippocampal formation is a key brain region for conscious memories in humans and other animals. Within the medial temporal lobe, information propagates through excitatory synapses from the superficial layers of the entorhinal cortex to the dentate gyrus, then to cornu ammonis 3, 2, and 1 and ultimately back to the deep entorhinal cortex. The dentate gyrus as the ‘input gate’ of the hippocampus is pivotal for controlling the propagation of excitation through the hippocampal network and this function is tightly controlled by different types of GABAergic interneurons. Various diseases, including Alzheimer's disease and temporal lobe epilepsy cause early death of dentate gyrus interneurons, hippocampal degeneration, and memory deficits. Recent studies indicate that abnormal electrical activity patterns, known as interictal epileptiform discharges, or ‘interictal spikes’ are a hallmark of both temporal lobe epilepsy and Alzheimer’s disease, and their occurrence is tightly linked to disrupted memory function. Aside of these interictal spikes, the dentate gyrus also produces physiological ‘dentate spikes’ in response to synchronized inputs from the entorhinal cortex, which are important for memory consolidation. In the current proposal, we aim to investigate the role of dentate gyrus interneurons in physiological dentate spikes and pathological interictal epileptiform discharges in a mouse model of Alzheimer’s disease, and probe the utility of closed loop optogenetic dentate gyrus interneuron stimulation to disrupt hippocampal interictal epileptiform discharges while preserving physiological dentate spikes, and alleviate memory deficits.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Gyorgy Buzsaki, Ph.D.