A proteomic analysis of contextual fear conditioned rats reveals dynamic modifications in neuron and oligodendrocyte protein expression in the dentate gyrus

Abstract

Contextual memory is an intricate process involving synaptic plasticity and network rearrangement. Both are governed by many molecular processes including phosphorylation and modulation of protein expression. However, little is known about the molecules involved in it. Here, we exploited the advantages of a quantitative proteomic approach to identify a great number of molecules in the rat dentate gyrus after a contextual fear conditioning session. Our results allowed us to highlight protein expression patterns, not only related to neuroplasticity, but also to myelin structure, such as myelin basic protein and myelin proteolipid protein showing a decrease in expression. Validation of the modification in protein expression reveals a dynamic profile during the 48 h following the fear conditioning session. The expression of proteins involved in neurite outgrowth, such as BASP-1 and calcineurin B1, and in synaptic structure and function, VAMP2 and RAB3C, was increased in the dentate gyrus of rats submitted to fear conditioning compared to controls. We showed that the increase in BASP-1 protein was specific to fear conditioning learning as it was not present in immediate-shock rats, neither in rats exposed to a novel environment without being shocked. As myelin is known to stabilise synaptic network, the decrease in myelin proteins suggests a neuroglia interactive process taking place in the dentate gyrus in the 24 h following contextual fear learning, which has never been demonstrated before. These results therefore open the way to the study of new plasticity mechanisms underlying learning and memory.

Synaptic activity–dependent changes in the hippocampal palmitoylome

“…6C). These results are consistent with a role for cFC in promoting plasticity-related changes in palmitoylation that are more broadly distributed across different cell types in the hippocampus ( 22 , 27 , 28 , 30 – 33 ).…”

“…No statistical methods were used to predetermine sample size. The sample size for the proteomic screen was based on previous work ( 9 , 22 , 23 , 62 ). No randomization was performed.…”

Distinct Transcriptomic Profiles in the Dorsal Hippocampus and Prelimbic Cortex Are Transiently Regulated following Episodic Learning

“…Perhaps myelin-based mechanisms first need to decrease to allow a subsequent increase in oligodendrocyte changes that would be needed to stabilize newly established connectivity. In line with this idea, a decrease in myelin proteins was reported by proteomic analysis of the dentate gyrus 24 h after contextual fear conditioning in mice (Houyoux et al, 2017). If our hypothesis is correct, it is possible that a delayed wave of oligodendrocyte transcript upregulation in the PL cortex may take place to support systems consolidation.…”

Metanalysis of genome-wide association studies for panic disorder suggest pathways and mechanisms of pathogenesis

“…The higher expression in MOs is of interest, since myelin is known to stabilize synaptic networks, 398 and oligodendrocyte-related proteins have been shown to be modified in the rat dentate gyrus 399 during contextual fear conditioning (Houyoux et al, 2017). Moreover, microglia has been shown to 400 participate in cued fear conditioning (Parkhurst et al, 2013), and microglial acid sensing has been 401 shown to participate in carbon dioxide-evoked fear (Vollmer et al, 2016).…”