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18 Nov 2019

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Research

Engram circuit mediates cocaine memory

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Memory is a fundamental capacity that plays a vital role in cognitive functioning. Where and how is a specific memory stored in the brain? This seemingly obvious theme in neuroscience has been intensively debated for centuries. 


A team led by Prof. Ma Lan from State Key Laboratory of Medical Neurobiology finds that the engram circuit from the ventral CA1 region of hippocampus (vCA1) to the core of nucleus accumbens (AcbC) mediates memory storage and the preferential synaptic strengthening of the vCA1→AcbC engram circuit evoked by cocaine conditioning mediates the retrieval of cocaine CPP memory. Based on these findings, they hypothesize that distinct memory is stored in the engram circuit. Their paper has been published on Nature Neuroscience under the title “A ventral CA1 to nucleus accumbens core engram circuit mediates conditioned place preference for cocaine” on November 12.


Recent studies on memory engram show that the sparsely distributed neuron ensembles, i.e. engram cells, serve as the cellular representation of memory traces. The population of engram cells related to a specific fear experience is later preferentially reactivated upon fear memory retrieval. It is hypothesized that memory engram cells retain information and are crucial for memory retrieval. The questions lie in how engram cells from different brain regions work collaboratively to encode and store memory, whether drug memory is stored by specific engram cells and whether they could be selectively erased by the manipulation of the engram cells.


By tagging engram cells that activated during cocaine conditioned place preference (CPP) training, the researchers find that cocaine engram cells in the vCA1 and the AcbC are required for the storage and retrieval of cocaine CPP memory. The control engram in vCA1 has no effect on the retrieval of cocaine CPP memory, suggesting that cocaine CPP memory is stored specifically in cocaine engram cells. VCA1 engram projects preferentially to the nucleus accumbens and the engram circuits from vCA1 to the AcbC are critical for memory retrieval.The vCA1 engram encodes distinct contextual information, and the AcbC engram stores both cocaine reward and the contextual information associated with it. Cocaine conditioning evokes preferential postsynaptic strengthening of the vCA1→AcbC engram circuit, which mediates the storage and retrieval of cocaine CPP memory.

vCA1 engram cells labeled during the acquisition of cocaine CPP memory

Drs Zhou Yiming and Zhu Huiwen, Ph.D. candidate Liu Zhiyuan are co-first authors of the paper, with Professor Ma Lan and Associate Professor Liu Xing being the corresponding authors. 


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