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Fluorescence Microscopy Journal Club

Projections From Neocortex Mediate Top-Down Control of Memory Retrieval

by Priyamvada Rajasethupathy, Sethuraman Sankaran, James H. Marshel, Christina K. Kim,Emily Ferenczi, Soo Yeun Lee, Andre Berndt, Charu Ramakrishnan, Anna Jaffe, Maisie Lo, Conor Liston & Karl Deisseroth

Nature 2015, 526, pp. 653-659

While great progress in understanding the molecular and physiological mechanisms of memory formation have been made at the synaptic level, little is known as to how populations of individual neurons form networks representing memory.

The authors provide an extensive study identifying a hypothesized, but previously unidentified, monosynaptic connection between the anterior cingulate region of the prefrontal cortex and the CA1 and CA3 regions of the hippocampus. Using a variety of techniques including imaging for anatomical tracing, electrophysiology, optogenetic stimulation in freely moving animals and 2P imaging and optogenetic stimulation of restrained animals in a virtual environment they demonstrate a functional connection between the AC and CA1 and CA3 that appears to play a role on contextual memory formation and retrieval.

Their work provides a guide to suggested approaches for performing a complete study of connectivity between brain regions for the purpose of understanding memory formation and retrieval. Their use of retrograde and anterograde labelling with optogenetic probes provides useful guidance in terms of utilizing this strategy for demonstrating functional connections.

The identification of the AC-CA monosynaptic connection furthers our understanding of memory formation in general, as well as having clinical implications for psychiatric disorders such as post-traumatic stress disorder, schizophrenia and drug addiction.