Memory Circuits Team (Michel van den Oever) and Alzheimer Team (Ronald van Kesteren) join forces to test how hyperactive interneurons affect the formation and reactivation of memory engrams. They receive a 300 k€ grant from Alzheimer Nederland to investigate this.
Recent findings support the idea that memories are stored and recalled through lasting physical changes in the brain, so-called memory engrams. Engrams are encoded by sparsely distributed populations of neurons that become activated during an experience and then strengthen their mutual connections to store the memory. These sparse neurons that harbor an engram are referred to as engram cells. Basal activity and excitability of neurons at the time of learning determine which cells become engram cells and which not.
Early neuronal hyperactivity is a well-described phenomenon in Alzheimer’s disease (AD) patients and in many mouse models of AD. Aberrant activation of neurons in AD may thus cause an impairment in engram cell formation or reactivation, which may in turn contribute to the inability to form or recall memories.
In this project, the researchers will specifically study how hyperactive parvalbumin (PV) interneurons disrupt the formation or reactivation of engram ensembles. They will then restore PV cell activity to normal levels and test if learning and memory improve. Finally, they will identify receptors or channels on PV cells that can be targeted in order to restore memory function in AD.
Supported by Alzheimer Nederland (grant WE.03-2020-05: Reviving Silent Memories in Alzheimer’s Disease)