Search bioRxiv⌕ Search

Biology subjects

Choi, D. I.

Publications and source records attributed to Choi, D. I..

4 recordsLinked to original sources

Synaptic engram underlies memory

Memory encoding cells, or engram cells, are sparsely distributed across the brain. Recent findings have shown that memory formation coincides with the strengthening of interregional synaptic connectivity between engram ensembles. However, whether this learning-induced synaptic reorganization causally supports memory, independently or in concert with heterosynaptic and intrinsic plasticity, remains elusive. Here we developed optically implemented spike-timing-dependent plasticity (oSTDP), which induces synaptic depression selectively at target synapses by controlling the relative timing of pre- and postsynaptic activity. In vivo application of oSTDP to the synapses between entorhinal cortex (EC) and dentate gyrus (DG) engram cells caused a significant synaptic depression and the resultant memory impairment. Our results demonstrate that plasticity of functional connectivity between memory-encoding ensembles causally underlies memory.

neuroscience↗

Astrocytic connection to engram neurons increased after learning

Astrocytes directly participate in learning and memory. However, the structural association between astrocytes and memory-encoding engram neurons after learning remains to be elucidated. We developed astrocyte-enhanced green fluorescent protein reconstitution across synaptic partners (eGRASP) to examine tripartite synapses between astrocytes and engram neurons. Using astrocyte-eGRASP, we found that astrocytes had increased connections to engram neurons after learning. Dendritic spines with astrocytic contacts showed enhanced morphology. Live-cell imaging of astrocyte-eGRASP revealed that astrocytic connections are stabilized by neuronal activity. These results indicate that astrocytes distinguish contact between engram neurons and generate engram-specific contact patterns during learning.

neuroscience↗

Hippocampal engram networks for fear memory recruit new synapses and modify pre-existing synapses in vivo.

As basic units of neural networks, ensembles of synapses underlie cognitive functions like learning and memory. These synaptic engrams show elevated synaptic density among engram cells following contextual fear memory formation. Subsequent analysis of the CA3-CA1 engram synapse revealed larger spine sizes, as the synaptic connectivity correlated to the memory strength. Here, we elucidate the synapse dynamics between CA3 and CA1 by tracking identical synapses at multiple time points by adapting two-photon microscopy and dual-eGRASP technique in vivo. After memory formation, synaptic connections between engram populations are enhanced in conjunction with synaptogenesis within the hippocampal network. However, extinction learning specifically correlated with the disappearance of CA3 engram to CA1 engram (E-E) synapses. We observed "newly formed" synapses near pre-existing synapses, which clustered CA3-CA1 engram synapses after fear memory formation. Overall, we conclude that dynamics at CA3 to CA1 E-E synapses are key sites for modification during fear memory states. HighlightsO_LIWe adapted four-color two-photon microscopy with dual-eGRASP for a longitudinal observation of synaptic connections between CA3 and CA1. C_LIO_LISynaptogenesis according to fear memory formation was specifically observed in E-E synapses. C_LIO_LIExtinction learning significantly correlated with the disappearance of E-E synapses. C_LIO_LIParticular distribution pattern of newly formed E-E synapses was observed after memory formation. C_LI

neuroscience↗

Synaptic correlates of associative fear memory in the lateral amygdala

Successful adaptation to the environment requires accurate responding to external threats by recalling specific memories. However, elucidating underlying neural substrates of associative fear memory was limited due to the difficulties in direct examination of extinction-induced changes of specific synapses that encode an auditory fear memory. Using dual-eGRASP (enhanced Green Fluorescent Protein Reconstitution Across Synaptic Partners), we found that synapses between engram cells or synaptic engram showed a significantly larger spine morphology at auditory cortex (AC) to lateral amygdala (LA) projections after auditory fear conditioning. Fear extinction reversed the enhanced synaptic engram spines while re-conditioning with the same tone and shock restored the size of the synaptic engram. Taken together, we suggest that the synaptic engram may represent a different state of fear memory. One Sentence SummaryAssociative fear memory enlarged the spine morphology of synapses between engram neurons in the amygdala, which was diminished by memory extinction and restored by re-conditioning, suggesting that connections between engram cells represent a different state of fear memory.

neuroscience↗