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

Krzisch M, Temprana SG, Mongiat LA, Armida J, Schmutz V, Virtanen MA, Kocher-Braissant J, Kraftsik R, Vutskits L, Conzelmann KK, Bergami M, Gage FH, Schinder AF, Toni N - Brain Struct Funct (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Fundamental Neurosciences, University of Lausanne, 9 rue du Bugnon, 1005, Lausanne, Switzerland.

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.

No MeSH data available.


Related in: MedlinePlus

Distribution of perisynaptic processes and of potential presynaptic partners. a Electron micrographs of dendritic spines from new neurons (30 dpi, false-colored in red) synapsing with an axon terminal (blue) and showing an astrocytic process (green) intercalated between the spine and a potential presynaptic partner (pink). Scale bar 0.5 µm. b–d Three-dimensional reconstructions of dendritic spines (red), their presynaptic partner (blue) and a potential presynaptic partner (pink), separated by an astrocytic process (green). For illustrative purpose, only one potential presynaptic partner and the portion of the astrocytic process intercalating between this terminal and the spine has been rendered. Scale bar 0.5 µm e Schematic representation of the average number of presynaptic terminals and astrocytic processes surrounding a dendritic spine from a new neuron (gray), showing four potential presynaptic partners (pink) and one synapsing axon terminal (blue). Perisynaptic processes (green) are shown, two of which intercalate between the spine and two potential presynaptic partners (arrows)
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Fig5: Distribution of perisynaptic processes and of potential presynaptic partners. a Electron micrographs of dendritic spines from new neurons (30 dpi, false-colored in red) synapsing with an axon terminal (blue) and showing an astrocytic process (green) intercalated between the spine and a potential presynaptic partner (pink). Scale bar 0.5 µm. b–d Three-dimensional reconstructions of dendritic spines (red), their presynaptic partner (blue) and a potential presynaptic partner (pink), separated by an astrocytic process (green). For illustrative purpose, only one potential presynaptic partner and the portion of the astrocytic process intercalating between this terminal and the spine has been rendered. Scale bar 0.5 µm e Schematic representation of the average number of presynaptic terminals and astrocytic processes surrounding a dendritic spine from a new neuron (gray), showing four potential presynaptic partners (pink) and one synapsing axon terminal (blue). Perisynaptic processes (green) are shown, two of which intercalate between the spine and two potential presynaptic partners (arrows)

Mentions: Dendritic spines rarely have a straight neck and do not necessarily synapse with the nearest axonal bouton. Since new neurons preferentially contact pre-existing axonal boutons (Toni et al. 2007, 2008), we hypothesized that astrocytic perisynaptic processes, by ensheathing pre-existing axons, may play a structural role in the connectivity of the spines of the newborn neurons. To assess this possibility, we examined the spatial distribution of astrocytic processes and axonal boutons in the vicinity of new dendritic spines. We used serial section electron microscopy and analyzed the volume within a radius of 1 μm around dendritic spines from new neurons at 30 dpi (n = 62 spines analyzed). We found that the distance between dendritic spines and the closest astrocytic process ranged between 0 and 100 nm and 81 % of the dendritic spines were touched by an astrocytic process, either on the head or on the neck (Fig. 5). On average, 5.4 axonal boutons were found in a radius of 1 μm from a given spine and could, in principle, make a synapse with it, thereby defining a connectivity fraction of 0.18, similar to the connectivity fraction reported for the CA1 area (Mishchenko et al. 2010) (boutons isolated from the spine by a dendrite or an axon, were not taken into account). For 34 spines for which the volume was fully reconstructed, the potential presynaptic partners not synapsing with the spine represented a total of 150 boutons. Of these, 109 were synapsing already with an unlabeled spine, indicating they were glutamatergic and functional and 41 were not completely comprised in the reconstructed volume. Three potential presynaptic partners were found to synapse with a dendrite, suggesting they were GABAergic and were removed from the analysis. More importantly, for 56 of 147 boutons (38 %, p = 0.005 for equal proportions H0), an astrocytic process was found intercalated between the boutons and the new spine (Fig. 5). Together, these results show that pre-existing perisynaptic processes intercalate between the new spines and some of their potential presynaptic partners and by doing so, may play a structural role in their connectivity by blocking the access of the spines to some of their potential partners.Fig. 5


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

Krzisch M, Temprana SG, Mongiat LA, Armida J, Schmutz V, Virtanen MA, Kocher-Braissant J, Kraftsik R, Vutskits L, Conzelmann KK, Bergami M, Gage FH, Schinder AF, Toni N - Brain Struct Funct (2014)

Distribution of perisynaptic processes and of potential presynaptic partners. a Electron micrographs of dendritic spines from new neurons (30 dpi, false-colored in red) synapsing with an axon terminal (blue) and showing an astrocytic process (green) intercalated between the spine and a potential presynaptic partner (pink). Scale bar 0.5 µm. b–d Three-dimensional reconstructions of dendritic spines (red), their presynaptic partner (blue) and a potential presynaptic partner (pink), separated by an astrocytic process (green). For illustrative purpose, only one potential presynaptic partner and the portion of the astrocytic process intercalating between this terminal and the spine has been rendered. Scale bar 0.5 µm e Schematic representation of the average number of presynaptic terminals and astrocytic processes surrounding a dendritic spine from a new neuron (gray), showing four potential presynaptic partners (pink) and one synapsing axon terminal (blue). Perisynaptic processes (green) are shown, two of which intercalate between the spine and two potential presynaptic partners (arrows)
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Related In: Results  -  Collection

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Fig5: Distribution of perisynaptic processes and of potential presynaptic partners. a Electron micrographs of dendritic spines from new neurons (30 dpi, false-colored in red) synapsing with an axon terminal (blue) and showing an astrocytic process (green) intercalated between the spine and a potential presynaptic partner (pink). Scale bar 0.5 µm. b–d Three-dimensional reconstructions of dendritic spines (red), their presynaptic partner (blue) and a potential presynaptic partner (pink), separated by an astrocytic process (green). For illustrative purpose, only one potential presynaptic partner and the portion of the astrocytic process intercalating between this terminal and the spine has been rendered. Scale bar 0.5 µm e Schematic representation of the average number of presynaptic terminals and astrocytic processes surrounding a dendritic spine from a new neuron (gray), showing four potential presynaptic partners (pink) and one synapsing axon terminal (blue). Perisynaptic processes (green) are shown, two of which intercalate between the spine and two potential presynaptic partners (arrows)
Mentions: Dendritic spines rarely have a straight neck and do not necessarily synapse with the nearest axonal bouton. Since new neurons preferentially contact pre-existing axonal boutons (Toni et al. 2007, 2008), we hypothesized that astrocytic perisynaptic processes, by ensheathing pre-existing axons, may play a structural role in the connectivity of the spines of the newborn neurons. To assess this possibility, we examined the spatial distribution of astrocytic processes and axonal boutons in the vicinity of new dendritic spines. We used serial section electron microscopy and analyzed the volume within a radius of 1 μm around dendritic spines from new neurons at 30 dpi (n = 62 spines analyzed). We found that the distance between dendritic spines and the closest astrocytic process ranged between 0 and 100 nm and 81 % of the dendritic spines were touched by an astrocytic process, either on the head or on the neck (Fig. 5). On average, 5.4 axonal boutons were found in a radius of 1 μm from a given spine and could, in principle, make a synapse with it, thereby defining a connectivity fraction of 0.18, similar to the connectivity fraction reported for the CA1 area (Mishchenko et al. 2010) (boutons isolated from the spine by a dendrite or an axon, were not taken into account). For 34 spines for which the volume was fully reconstructed, the potential presynaptic partners not synapsing with the spine represented a total of 150 boutons. Of these, 109 were synapsing already with an unlabeled spine, indicating they were glutamatergic and functional and 41 were not completely comprised in the reconstructed volume. Three potential presynaptic partners were found to synapse with a dendrite, suggesting they were GABAergic and were removed from the analysis. More importantly, for 56 of 147 boutons (38 %, p = 0.005 for equal proportions H0), an astrocytic process was found intercalated between the boutons and the new spine (Fig. 5). Together, these results show that pre-existing perisynaptic processes intercalate between the new spines and some of their potential presynaptic partners and by doing so, may play a structural role in their connectivity by blocking the access of the spines to some of their potential partners.Fig. 5

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Fundamental Neurosciences, University of Lausanne, 9 rue du Bugnon, 1005, Lausanne, Switzerland.

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.

No MeSH data available.


Related in: MedlinePlus