Synaptopodin regulates denervation-induced plasticity at hippocampal mossy fiber synapses

Neurological diseases can lead to the denervation of brain regions caused
by demyelination, traumatic injury or cell death. The molecular and
structural mechanisms underlying lesion-induced reorganization of
denervated brain regions, however, are a matter of ongoing investigation.
In order to address this issue, we performed an entorhinal cortex lesion
(ECL) in mouse organotypic entorhino-hippocampal tissue cultures of both
sexes and studied denervation-induced plasticity of mossy fiber synapses,
which connect dentate granule cells (dGCs) with CA3 pyramidal cells
(CA3-PCs) and play important roles in learning and memory formation.
Partial denervation caused a strengthening of excitatory neurotransmission
in dGCs, CA3-PCs and their direct synaptic connections, as revealed by
paired recordings (dGC-to-CA3-PC). These functional changes were
accompanied by ultrastructural reorganization of mossy fiber synapses,
which regularly contain the plasticity-regulating protein synaptopodin and
the spine apparatus organelle. We demonstrate that the spine apparatus
organelle and synaptopodin are related to ribosomes in close proximity to
synaptic sites and unravel a synaptopodin-related transcriptome. Notably,
synaptopodin-deficient tissue preparations that lack the spine apparatus
organelle failed to express lesion-induced synaptic adjustments. Hence,
synaptopodin and the spine apparatus organelle play a crucial role in
regulating lesion-induced synaptic plasticity at hippocampal mossy fiber
synapses.