Perineuronal nets affect memory and learning after synapse withdrawal

Abstract

Perineuronal nets (PNNs) enwrap mature neurons, playing a role in the control of plasticity and synapse dynamics. PNNs have been shown to have effects on memory formation, retention and extinction in a variety of animal models. It has been proposed that the cavities in PNNs, which contain synapses, can act as a memory store and that they remain stable after events that cause synaptic withdrawal such as anoxia or hibernation. We examine this idea by monitoring place memory before and after synaptic withdrawal caused by acute hibernation-like state (HLS). Animals lacking hippocampal PNNs due to enzymatic digestion by chondroitinase ABC or knockout of the PNN component aggrecan were compared with wild type controls. HLS-induced synapse withdrawal caused a memory deficit, but not to the level of untreated naïve animals and not worsened by PNN attenuation. After HLS, only animals lacking PNNs showed memory restoration or relearning. Absence of PNNs affected the restoration of excitatory synapses on PNN-bearing neurons. The results support a role for hippocampal PNNs in learning, but not in long-term memory storage for correction of deficits.

Developmental disruption ofMef2cin Medial Ganglionic Eminence-derived cortical inhibitory interneurons impairs cellular and circuit function

“…Lhx6 cHet animals, while not having MGE-IN cell loss (Figure 1H, Figure S1F-H), had reduced number of PV + cells in V1 (Figure 1E). We also assessed the presence of perineuronal nets (PNNs) surrounding PV-INs in V1, as the appearance of these extracellular matrix structures coincides with an increase in PV expression (26-29). We found that embryonic removal of Mef2c from MGE-INs leads to a reduction in the presence of PNNs (Figure 1I, J).…”

Prelimbic cortex perineuronal net expression and social behavior: Impact of adolescent intermittent ethanol exposure

“…PNNs are thought to regulate the formation of synapses on the cells they encompass (Ruzicka et al, 2022), and given that the excitatory/inhibitory balance in the PFC is remodeled during adolescence (Caballero et al, 2021), we were interested in assessing whether AIE resulted in alterations of excitatory/inhibitory puncta synapsing on PNNs. Using immunofluorescence and confocal imaging, we quantified the number of vGlut2 and vGat puncta proximal to PNN surfaces (Fig.…”

The Role of Cerebellar Intrinsic Neuronal Excitability, Synaptic Plasticity, and Perineuronal Nets in Eyeblink Conditioning

“…As in other preparations, there is a growing consensus that both intrinsic membrane excitability and synaptic plasticity are required for eyeblink conditioning [ 88 , 99 , 101 , 114 , 117 , 121 , 122 , 123 , 131 , 132 , 199 , 258 , 259 , 260 , 261 , 262 , 263 ]. More recently, there is a growing consensus that perineuronal nets are also involved in learning and memory across a range of paradigms [ 210 , 264 , 265 , 266 , 267 , 268 , 269 , 270 ], including fear conditioning [ 271 , 272 , 273 , 274 , 275 , 276 , 277 , 278 ] and eyeblink conditioning [ 86 , 200 , 201 , 202 , 203 , 257 ]. Together, these findings provide evidence for the combined role of intrinsic membrane excitability, synaptic plasticity, and the perineuronal net in eyeblink conditioning.…”