Clustered Loss of Dendritic Spines Characterizes Encoding of Related Memory

Abstract

Generation of new spines is often thought of as a correlate of memory and loss of spines is considered representing memory loss. Contrary to common belief, we observe that spine loss has functional value in distinctly encoding related life events rather than causing memory loss. Using spatial autocorrelation of dendritic morphology obtained from in vivo longitudinal imaging, we show that clustered loss, rather than gain, of new spines characterizes the formation of related memory. This spatially selective dendritic spine loss occurs closer to new spines formed during the acquisition of initial memory. Thus, enabling the dendrites to store multiple memories and their inter relationship. Remarkably, we find acquisition of related memory in the absence of NMDAR activation increases the fraction of such correlated spine loss.

Heterosynaptic Plasticity and the Experience-Dependent Refinement of Developing Neuronal Circuits

“…The argument for the involvement of heterosynaptic plasticity in synaptic remodeling has been strengthened in vivo by the advance of longitudinal two-photon imaging of dendritic spines. Numerous studies performed over development and learning have shown that the rate of dendritic spine turnover and formation is strongly dependent on experience (Trachtenberg et al, 2002 ; Holtmaat et al, 2005 ; Zuo et al, 2005a , b ; Hofer et al, 2009 ; Xu et al, 2009 ; Chen et al, 2012 ; Fu et al, 2012 ; Lai et al, 2012 ; van Versendaal et al, 2012 ; Yang et al, 2014 , 2016 ; Miquelajauregui et al, 2015 ; Barnes et al, 2017 ; El-Boustani et al, 2018 ; Frank et al, 2018 ; Jungenitz et al, 2018 ; Kumar et al, 2020 ). The experience-dependence of synaptic dynamics is consistent across different brain areas and occurs for both excitatory and inhibitory synapses.…”

“…Novel experiences can promote clustered spine formation (Fu et al, 2012 ; Yang et al, 2014 , 2016 ; Frank et al, 2018 ; Kumar et al, 2020 ), and clustered spine elimination can also occur in response to learning, as well as during sensory enrichment and deprivation (Chen et al, 2012 ; Lai et al, 2012 ; Frank et al, 2018 ; Kumar et al, 2020 ). Some studies have found that clustered spine elimination is related to encoding specific information such as familiar memories (Kumar et al, 2020 ) or fear conditioning (Lai et al, 2012 ). Frank et al ( 2018 ) have suggested that experience-dependent spine elimination could facilitate clustered spine formation during learning.…”