Dendritic distribution of autophagosomes underlies pathway-selective induction of LTD.

Kevin M Keary, Qin-Hua Gu, Jiji Chen, Zheng Li

Cell reports 2023 Aug 29

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The mechanism of long-term depression (LTD), a cellular substrate for learning, memory, and behavioral flexibility, is extensively studied in Schaffer collateral (SC) synapses, with inhibition of autophagy identified as a key factor. SC inputs terminate at basal and proximal apical dendrites, whereas distal apical dendrites receive inputs from the temporoammonic pathway (TAP). Here, we demonstrate that TAP and SC synapses have a shared LTD mechanism reliant on NMDA receptors, caspase-3, and autophagy inhibition. Despite this shared LTD mechanism, proximal apical dendrites contain more autophagosomes than distal apical dendrites. Additionally, unlike SC LTD, which diminishes with age, TAP LTD persists into adulthood. Our previous study shows that the high autophagy in adulthood disallows SC LTD induction. The reduction of autophagosomes from proximal to distal dendrites, combined with distinct LTD inducibility at SC and TAP synapses, suggests a model where the differential distribution of autophagosomes in dendrites gates LTD inducibility at specific circuits. Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Kevin M Keary, Qin-Hua Gu, Jiji Chen, Zheng Li. Dendritic distribution of autophagosomes underlies pathway-selective induction of LTD. Cell reports. 2023 Aug 29;42(8):112898