Neurofilament Levels in Dendritic Spines Associate with Synaptic Status

Abstract

Neurofilaments are one of the main cytoskeletal components in neurons; they can be found in the form of oligomers at pre- and postsynapses. How their presence is regulated at the postsynapse remains largely unclear. Here we systematically quantified, by immunolabeling, the occurrence of the neurofilament isoform triplet neurofilament light (NFL), medium (NFM), and heavy (NFH) at the postsynapse using STED nanoscopy together with markers of synaptic strength and activity. Our data show that, within dendritic spines, neurofilament isoforms rarely colocalize with each other and that they are present to different extents, with NFL being the most abundant isoform. The amount of the three isoforms correlates with markers of postsynaptic strength and presynaptic activity to varying degrees: NFL shows the highest correlation to both synaptic traits, suggesting its involvement in synaptic response, while NFM exhibits the lowest correlations. By quantifying the presence of neurofilaments at the postsynapse within the context of the synaptic status, this work sheds new light on the regulation of synaptic neurofilaments and their possible contribution to synaptopathies.

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“…Neurofilaments play essential roles in axonal growth, stability, maintenance of mitochondrial stability, and microtubule content [ 69 ]. Additionally, distinct neurofilament isoforms have been discovered to maintain the structure and function of dendritic spines associated with the synaptic status [ 70 ].…”

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“…However, neurofilaments (10 nm diam. or intermediate filaments) have been found in the typical, squid neuron cell somata [222] while, in mammals and humans, they seemed to be normally also confined to dendrites and synaptic structures [223] and were in the AIS of neuropathologic cases [224]. However, these fibrillar components have been parts of neurotubule fascicles and part of the electron dense finely granular material undercoating of the axolemma along with dispersed ribosomes with early fine structure descriptions of neurons, albeit without identifying the marker (as reported in [159]).…”

Paralemmin-1 controls the nanoarchitecture of the neuronal submembrane cytoskeleton

“…Statistical tests are described in each caption. Correlation coefficients were interpreted as suggested in60 : 0.0-0.3 no correlation, 0.3-0.5 low correlation, 0.5-0.7 moderate correlation, 0.7-1 high correlation. Statistical differences are indicated as follows: * = p<0.05; ** = p<0.005, *** = p<0.005.…”