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Recurrent rewiring of the adult hippocampal mossy fiber system by a single transcriptional regulator, Id2

ABSTRACT: Recurrent rewiring of the adult hippocampal mossy fiber system by a single transcriptional regulator, Id2

PROVIDER: PRJNA678956 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13073200_1.fastq.gz	Fastqsanger.gz
	SRR13073200_2.fastq.gz	Fastqsanger.gz
	SRR13073300_1.fastq.gz	Fastqsanger.gz
	SRR13073300_2.fastq.gz	Fastqsanger.gz
	SRR13073400_1.fastq.gz	Fastqsanger.gz

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Recurrent rewiring of the adult hippocampal mossy fiber system by a single transcriptional regulator, Id2

Project description:Circuit formation in the central nervous system has been historically studied during development, after which cell-autonomous and nonautonomous wiring factors inactivate. In principle, balanced reactivation of such factors could enable further wiring in adults, but their relative contributions may be circuit dependent and are largely unknown. Here, we investigated hippocampal mossy fiber sprouting to gain insight into wiring mechanisms in mature circuits. We found that sole ectopic expression of Id2 in granule cells is capable of driving mossy fiber sprouting in healthy adult mouse and rat. Mice with the new mossy fiber circuit solved spatial problems equally well as controls but appeared to rely on local rather than global spatial cues. Our results demonstrate reprogrammed connectivity in mature neurons by one defined factor and an assembly of a new synaptic circuit in adult brain.

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Project description:Neurological diseases can lead to the denervation of brain regions caused by demyelination, traumatic injury or cell death. Nevertheless, the molecular and structural mechanisms underlying lesion-induced reorganization of denervated brain regions 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 spatial learning. Partial denervation caused a strengthening of excitatory neurotransmission in dGCs, in CA3-PCs, and their direct synaptic connections as revealed by paired recordings (GC-to-CA3). These functional changes were accompanied by ultrastructural reorganization of mossy fiber synapses, which regularly contain the plasticity-related protein synaptopodin and the spine apparatus organelle. We demonstrate that the spine apparatus organelle and its integral protein synaptopodin are associated with 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.

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