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Pre-existing astrocytes form functional perisynaptic processes on neurons generated in the adult hippocampus.

ABSTRACT: The adult dentate gyrus produces new neurons that morphologically and functionally integrate into the hippocampal network. In the adult brain, most excitatory synapses are ensheathed by astrocytic perisynaptic processes that regulate synaptic structure and function. However, these processes are formed during embryonic or early postnatal development and it is unknown whether astrocytes can also ensheathe synapses of neurons born during adulthood and, if so, whether they play a role in their synaptic transmission. Here, we used a combination of serial-section immuno-electron microscopy, confocal microscopy, and electrophysiology to examine the formation of perisynaptic processes on adult-born neurons. We found that the afferent and efferent synapses of newborn neurons are ensheathed by astrocytic processes, irrespective of the age of the neurons or the size of their synapses. The quantification of gliogenesis and the distribution of astrocytic processes on synapses formed by adult-born neurons suggest that the majority of these processes are recruited from pre-existing astrocytes. Furthermore, the inhibition of astrocytic glutamate re-uptake significantly reduced postsynaptic currents and increased paired-pulse facilitation in adult-born neurons, suggesting that perisynaptic processes modulate synaptic transmission on these cells. Finally, some processes were found intercalated between newly formed dendritic spines and potential presynaptic partners, suggesting that they may also play a structural role in the connectivity of new spines. Together, these results indicate that pre-existing astrocytes remodel their processes to ensheathe synapses of adult-born neurons and participate to the functional and structural integration of these cells into the hippocampal network.

SUBMITTER: Krzisch M

PROVIDER: S-EPMC4481333 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Local translation is a conserved molecular mechanism. It allows a cell with a complex shape to bypass somatic protein synthesis and transport, and thus to respond quickly to a local stimulus. Local translation also contributes to the establishment of molecular and functional polarity. In the brain, it has been extensively studied in neurons and has also been described more recently in astrocytes - a type of glial cell with specialized extensions that contact vessels and synapses. Here, we studied perisynaptic astrocytic processes (PAPs) in the dorsal hippocampus and showed that they contain RNAs, ribosomes, the endoplasmic reticulum-Golgi intermediate compartment, particles of the Golgi apparatus, and protein synthesis events. We used our recently refined polysome immunoprecipitation technique to characterize the pool of polysomal mRNAs in PAPs (which we refer to as the “PAPome”) from the dorsal hippocampus and compared it with the polysomal mRNAs found in the astrocyte as a whole. The polysomal transcripts that were enriched in the PAPome encoded mostly cytoplasmic proteins and defined an unexpected molecular repertoire with the most enriched transcripts coding for proteins involved in iron homeostasis, translation, cell cycle and cytoskeleton. Interestingly, among them Erz, Fth1, and Rplp1 were enriched in PAPs compared to perivascular astrocytic processes indicating that local translation differ at these two interfaces and may sustain distinct molecular properties. The PAP-enriched transcripts Flt1, Fth1, Ccnd2, Mdm2, Gnb2l1 and Eef1a1 code for proteins involved in memory and learning mechanisms. We therefore studied their local translation in the context of fear conditioning (i.e. behavior involving the dorsal hippocampus). We observed changes in the density and/or distribution of these mRNAs in astrocytes processes as well as a drop of their translation specifically in PAPs. Our results highlight unexpected molecular properties of hippocampal PAPs and suggest for the first time that local translation in this perisynaptic compartment is linked to fear-related memory.

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Pre-existing astrocytes form functional perisynaptic processes on neurons generated in the adult hippocampus.

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