Resources
Authors & Affiliations
Andrin Abegg, Matteo Ranucci, Kanako Otomo, Alex Rosi-Andersen, Shiva Tyagarajan, Theofanis Karayannis
Abstract
Although excitatory cells comprise the bulk of hippocampal neurons, roughly 20 percent of the neuronal population is inhibitory. While an increasing interest in inhibitory signaling has led to the discovery of its importance for controlling episodic memory encoding and consolidation, its contribution to the function of individual engram neurons is largely unknown. In this project, we study GABAergic inhibitory synaptic plasticity in hippocampal engram neurons and its function in memory precision. We employ the Fos-TRAP2 system to label and manipulate contextual fear memory engrams in mice. We demonstrate that engram neurons in the dentate gyrus display a transient potentiation of perisomatic inhibitory input lasting approximately three weeks after initial memory encoding. This window of increased engram inhibition correlates with increased contextual memory precision. By using AAV-based tools to manipulate and introduce variants of gephyrin -a key inhibitory postsynaptic organizer- specifically in engram neurons, we show that we can change the time course of memory precision. In summary, this project studies the importance of the inhibitory system in shaping episodic memory function through the synaptic plasticity of engram cells.