The temporal pattern of synaptic activation determines the longevity of structural plasticity at dendritic spines

Homosynaptic plasticity induction causes heterosynaptic changes at the unstimulated neighbors in an induction pattern and location-specific manner

“…We previously showed that temporal uncaging patterns derived from the same Poisson distribution with the same number of uncaging pulses as the regular train (30 pulses) induced plasticity at stimulated spines in a pattern-specific manner (Argunsah and Israely, 2023 ). Here, we expanded upon that idea by analyzing the volumes of the unstimulated neighbors surrounding the stimulated spines up to 15 μm in either direction along the dendrite ( Figure 1C ) and up to 4 h post-homosynaptic plasticity induction ( Figure 1D ).…”

“…In order to have some diversity, we chose one train that had 10 pulses every 20 s (NSP-Uni), another one that had 15 pulses in the first 20 s and another 15 in the last 20 (NSP-Beg), skewing more to the beginning of the stimulation, and the last one had 15 pulses in the first 40 s and 15 in the last 20 (NSP-End), skewing to the end of the stimulation. The details of the generation of these pulse trains can be found in Argunsah and Israely ( 2023 ) and the Matlab code to generate naturalistic uncaging patterns for induction of plasticity is publicly available. 1…”

“…A widely used paradigm for the induction of long-term potentiation (LTP) at single spines involves light-mediated delivery of 30 pulses of glutamate (4 ms-long pulse-width, at 0.5 Hz, lasting 60 s; Kruijssen and Wierenga, 2019 ), which we will refer to as 30-Reg (Reg: Regularly spaced; Harvey and Svoboda, 2007 ; Harvey et al, 2008 ; Govindarajan et al, 2011 ; Hobbiss et al, 2018 ; Argunsah and Israely, 2023 ). This 30-Reg paradigm has been shown to induce LTP at single dendritic spines and depending on the availability of plasticity-related proteins (PRP), this form of plasticity could lead to either E-LTP or L-LTP (Govindarajan et al, 2011 ; Argunsah and Israely, 2023 ). Many signaling pathways at single spines have been studied based on the structural LTP (sLTP) induced by this particular pattern (Harvey et al, 2008 ; Lee et al, 2009 ; Zhai et al, 2013 ; Bosch et al, 2014 ; Chang et al, 2017 ).…”

“…Neighboring dendritic spines have often been used as unstimulated controls and have repeatedly been shown to not undergo drastic changes upon the expression of homosynaptic plasticity at a stimulated neighbor (Matsuzaki et al, 2004 ; Harvey and Svoboda, 2007 ; Govindarajan et al, 2011 ). Although these 30-Reg stimulation-based studies have shaped our understanding of single spine structural plasticity mechanisms, endogenous neuronal firing patterns are not composed of inter-spike intervals with that degree of regularity (Zador and Dobrunz, 1997 ; Paulsen and Sejnowski, 2000 ; Frerking et al, 2005 ; Argunsah and Israely, 2023 ).…”

“…We have recently shown that uncaging patterns that are modeled after a Poisson process (termed naturalistic stimulation patterns or NSPs) induce diverse homosynaptic plastic changes at stimulated single dendritic spines (Argunsah and Israely, 2023 ). Here, we further analyzed our data to see whether unstimulated neighboring spines of NSP-stimulated synapses showed similar plasticity compartmentalization as is the case for neighbors of spines stimulated with the 30-Reg pattern.…”