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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

Pre-existing astrocytes ensheathe synapses from adult-born neurons. a, b Confocal micrographs and orthogonal projections of hippocampal sections immunostained for BrdU and NeuN (a) and BrdU and GFAP/S100β (Astro). (b). Scale bar 5 µm. c Scatter plot showing the number of astrocytic territories intersected by newborn neurons, as a function of their normalized dendritic extension (Spearman’s rank correlation test, p < 0.0001, R2 = 0.64, n = 6–26 neurons per timepoint, 85 neurons in total). d Confocal micrographs of newborn neurons (red) in GFAP-GFP mice (left panels) and Aldh1l1-GFP mice (right panels), illustrating one neuron intersecting the territory of several astrocytes (upper panels, arrows) and several neurons intersecting the territory of the same astrocyte (in white squares, lower panels). Scale bars 20 µm. e Electron micrographs of MSBs (stars) formed by the spine of a newborn neuron (dark immunolabeling) and ensheathed by a perisynaptic process (false-colored in green). Arrowheads point to dendritic spines. f 3D reconstruction of the MSB illustrated in the lowerpanel of eScale bars in e and f 0.5 µm. g Electron micrographs of MFT from new neurons (dark immunolabelling, false-colored in red) synapsing with the dendrite or thorny excrescence of a CA3 pyramidal cell (not colorized) that synapse with another non-labeled MFT (blue). The perisynaptic processes are colored in green. h 3D reconstruction of a perisynaptic process (green) ensheathing a MFT from a new neuron (red) and from a non-labeled neuron (blue). Scale bars in g and h 1 µm
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Fig3: Pre-existing astrocytes ensheathe synapses from adult-born neurons. a, b Confocal micrographs and orthogonal projections of hippocampal sections immunostained for BrdU and NeuN (a) and BrdU and GFAP/S100β (Astro). (b). Scale bar 5 µm. c Scatter plot showing the number of astrocytic territories intersected by newborn neurons, as a function of their normalized dendritic extension (Spearman’s rank correlation test, p < 0.0001, R2 = 0.64, n = 6–26 neurons per timepoint, 85 neurons in total). d Confocal micrographs of newborn neurons (red) in GFAP-GFP mice (left panels) and Aldh1l1-GFP mice (right panels), illustrating one neuron intersecting the territory of several astrocytes (upper panels, arrows) and several neurons intersecting the territory of the same astrocyte (in white squares, lower panels). Scale bars 20 µm. e Electron micrographs of MSBs (stars) formed by the spine of a newborn neuron (dark immunolabeling) and ensheathed by a perisynaptic process (false-colored in green). Arrowheads point to dendritic spines. f 3D reconstruction of the MSB illustrated in the lowerpanel of eScale bars in e and f 0.5 µm. g Electron micrographs of MFT from new neurons (dark immunolabelling, false-colored in red) synapsing with the dendrite or thorny excrescence of a CA3 pyramidal cell (not colorized) that synapse with another non-labeled MFT (blue). The perisynaptic processes are colored in green. h 3D reconstruction of a perisynaptic process (green) ensheathing a MFT from a new neuron (red) and from a non-labeled neuron (blue). Scale bars in g and h 1 µm

Mentions: To determine the number of astrocytes potentially contacting a newborn neuron (Fig. 3), we did not use GFAP immunostaining, which labels only the largest processes. We, therefore, used GFAP-GFP mice to measure the mean radius of astrocytes, i.e., the average of the distance between the nucleus and the border of its territory. We analyzed 37 astrocytes from 6 GFAP-GFP mice. We then used Aldh1l1-GFP mice to assess the number of astrocytic territories crossed by an individual newborn neuron. When the distance between the nucleus of a labeled astrocyte and a dendrite of an adult-born neuron was less than or equal to the average radius of an astrocytic territory, astrocytes were likely contacting the identified neuron.


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)

Pre-existing astrocytes ensheathe synapses from adult-born neurons. a, b Confocal micrographs and orthogonal projections of hippocampal sections immunostained for BrdU and NeuN (a) and BrdU and GFAP/S100β (Astro). (b). Scale bar 5 µm. c Scatter plot showing the number of astrocytic territories intersected by newborn neurons, as a function of their normalized dendritic extension (Spearman’s rank correlation test, p < 0.0001, R2 = 0.64, n = 6–26 neurons per timepoint, 85 neurons in total). d Confocal micrographs of newborn neurons (red) in GFAP-GFP mice (left panels) and Aldh1l1-GFP mice (right panels), illustrating one neuron intersecting the territory of several astrocytes (upper panels, arrows) and several neurons intersecting the territory of the same astrocyte (in white squares, lower panels). Scale bars 20 µm. e Electron micrographs of MSBs (stars) formed by the spine of a newborn neuron (dark immunolabeling) and ensheathed by a perisynaptic process (false-colored in green). Arrowheads point to dendritic spines. f 3D reconstruction of the MSB illustrated in the lowerpanel of eScale bars in e and f 0.5 µm. g Electron micrographs of MFT from new neurons (dark immunolabelling, false-colored in red) synapsing with the dendrite or thorny excrescence of a CA3 pyramidal cell (not colorized) that synapse with another non-labeled MFT (blue). The perisynaptic processes are colored in green. h 3D reconstruction of a perisynaptic process (green) ensheathing a MFT from a new neuron (red) and from a non-labeled neuron (blue). Scale bars in g and h 1 µm
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Related In: Results  -  Collection

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Fig3: Pre-existing astrocytes ensheathe synapses from adult-born neurons. a, b Confocal micrographs and orthogonal projections of hippocampal sections immunostained for BrdU and NeuN (a) and BrdU and GFAP/S100β (Astro). (b). Scale bar 5 µm. c Scatter plot showing the number of astrocytic territories intersected by newborn neurons, as a function of their normalized dendritic extension (Spearman’s rank correlation test, p < 0.0001, R2 = 0.64, n = 6–26 neurons per timepoint, 85 neurons in total). d Confocal micrographs of newborn neurons (red) in GFAP-GFP mice (left panels) and Aldh1l1-GFP mice (right panels), illustrating one neuron intersecting the territory of several astrocytes (upper panels, arrows) and several neurons intersecting the territory of the same astrocyte (in white squares, lower panels). Scale bars 20 µm. e Electron micrographs of MSBs (stars) formed by the spine of a newborn neuron (dark immunolabeling) and ensheathed by a perisynaptic process (false-colored in green). Arrowheads point to dendritic spines. f 3D reconstruction of the MSB illustrated in the lowerpanel of eScale bars in e and f 0.5 µm. g Electron micrographs of MFT from new neurons (dark immunolabelling, false-colored in red) synapsing with the dendrite or thorny excrescence of a CA3 pyramidal cell (not colorized) that synapse with another non-labeled MFT (blue). The perisynaptic processes are colored in green. h 3D reconstruction of a perisynaptic process (green) ensheathing a MFT from a new neuron (red) and from a non-labeled neuron (blue). Scale bars in g and h 1 µm
Mentions: To determine the number of astrocytes potentially contacting a newborn neuron (Fig. 3), we did not use GFAP immunostaining, which labels only the largest processes. We, therefore, used GFAP-GFP mice to measure the mean radius of astrocytes, i.e., the average of the distance between the nucleus and the border of its territory. We analyzed 37 astrocytes from 6 GFAP-GFP mice. We then used Aldh1l1-GFP mice to assess the number of astrocytic territories crossed by an individual newborn neuron. When the distance between the nucleus of a labeled astrocyte and a dendrite of an adult-born neuron was less than or equal to the average radius of an astrocytic territory, astrocytes were likely contacting the identified neuron.

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