Pignatelli's talk on Hippocampal engram

January 9, 2017

Engram Cell Connectivity as a Cellular Substrate for Memory Storage

January 9th, 2017, 4 p.m., Y55H12

Dr. Michele Pignatelli 

Tonegawa Lab

The Picower Institute for Learning and Memory

Massachusetts Institute of Techonology, USA

Abstract:

The storage of information refers to the systematic process of collecting and cataloging data so that they can be retrieved on request. To date, memory storage has mainly been investigated by pharmacological or molecular manipulation and by correlating synaptic changes with the strength of memory recall. Only recently it has become possible to specifically tag cells activated by learning. By using a learning-induced tagging strategy we expressed channelrhodopsin in a sparse population of learning-activated cells: engram cells. The opsin allowed for the artificial reactivation of the cellular population labeled during learning and resulted in memory retrieval. The same tagging strategy also verified the reactivation of engram cells upon presentation of retrieval cues. Engram cells displayed changes in synaptic weight typical of LTP such as high current amplitude, insertion of AMPA receptors, high spontaneous excitatory post-synaptic current frequency and amplitude, and increased dendritic spine density. These changes were blocked by the systemic injection of protein synthesis inhibitors (PSI) specifically within the consolidation window. However, optogenetic activation of engram cells in PSI-injected mice elicited full memory recall. Engram cells from the dentate gyrus established preferential connections with engram cells in the downstream hippocampal CA3 region in a feedforward excitatory engram cell circuit. This preferential connectivity was maintained in mice rendered amnesic by treatment with PSI within the consolidation window, suggesting that memory storage may survive retrograde amnesia in the form of a neural connectivity pattern.