Dendritic distribution of autophagosomes underlies pathway-selective induction of LTD

• Published in: Cell reports (Cambridge) Vol. 42; no. 8; p. 112898
• Main Authors: Keary, Kevin M., Gu, Qin-Hua, Chen, Jiji, Li, Zheng
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 29.08.2023; Elsevier
• Subjects: autophagy; CA1; caspase-3; CP: Neuroscience; dendrites; hippocampus; LTD; synaptic plasticity; temporoammonic pathway; CA1; autophagy; hippocampus; CP: Neuroscience; dendrites; synaptic plasticity; temporoammonic pathway; LTD; caspase-3
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.112898

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. [Display omitted] •TAP and SC synapses have a shared mechanism of LTD reliant on autophagy inhibition•Proximal apical dendrites have more autophagosomes than distal apical dendrites•TAP LTD persists into adulthood, whereas SC LTD does not Keary III et al. find that distinct circuits synapsing onto different parts of the same CA1 apical dendrite require autophagy inhibition for LTD. There are differing profiles of LTD inducibility correlating with a gradient of autophagosomes from proximal to distal dendrites. Autophagosome density may be a factor determining LTD inducibility.