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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

Astrocytic perisynaptic processes ensheathe MFT of adult-born neurons. a Electron micrographs of astrocytic processes (false-colored in green) ensheathing synapses between axon terminals of 56 dpi adult-born neurons (red) and dendrites or thorny excrescences of CA3 pyramidal neurons (blue). The perisynaptic ensheathement covers the presynaptic bouton (left panel) or both the presynaptic terminal and the dendrite (right panel). Arrows indicate glycogen granules; arrowheads indicate cytoskeletal filaments. b Three-dimensional reconstruction of a synapse between the dendrite of a CA3 pyramidal neuron (white) and the axon terminal of a newborn neuron (red), ensheathed by an astrocytic process (green). c Confocal micrographs showing contacts between the MFT of a 56 dpi adult-born neuron and astrocytic processes. Left panel maximal intensity projection (after deconvolution). Right panel single focal plane and orthogonal projections. d Distribution of the proportion of the surface of MFT covered by astrocytic processes, as a function of MFT area and neuronal age (Spearman’s Rank correlation test, p = 0.25, R2 = 0.01, n = 5–12 MFT per timepoint). Scale bars in a and b 1 µm, in c 2 µm
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Fig2: Astrocytic perisynaptic processes ensheathe MFT of adult-born neurons. a Electron micrographs of astrocytic processes (false-colored in green) ensheathing synapses between axon terminals of 56 dpi adult-born neurons (red) and dendrites or thorny excrescences of CA3 pyramidal neurons (blue). The perisynaptic ensheathement covers the presynaptic bouton (left panel) or both the presynaptic terminal and the dendrite (right panel). Arrows indicate glycogen granules; arrowheads indicate cytoskeletal filaments. b Three-dimensional reconstruction of a synapse between the dendrite of a CA3 pyramidal neuron (white) and the axon terminal of a newborn neuron (red), ensheathed by an astrocytic process (green). c Confocal micrographs showing contacts between the MFT of a 56 dpi adult-born neuron and astrocytic processes. Left panel maximal intensity projection (after deconvolution). Right panel single focal plane and orthogonal projections. d Distribution of the proportion of the surface of MFT covered by astrocytic processes, as a function of MFT area and neuronal age (Spearman’s Rank correlation test, p = 0.25, R2 = 0.01, n = 5–12 MFT per timepoint). Scale bars in a and b 1 µm, in c 2 µm

Mentions: Finally, we examined the astrocytic ensheathment on the efferent synapses of the new neurons in the CA3 area, i.e., the mossy fiber terminals (MFT). Using serial-section electron microscopy, we analyzed 27 MFT and found that all but one were ensheathed by astrocytic perisynaptic processes (Fig. 2a, b) that covered either the terminal only (1 of 26 boutons, Fig. 2a left panel) or both the dendrite and the terminal (25 of 26 boutons, Fig. 2a right panel and Fig. 2b). Consistently with previous observations in the CA3, astrocytic processes were tightly apposed to the MFT or the dendritic shaft but never touched thorny excrescences or synaptic clefts, which were engulfed in the MFT (Rollenhagen et al. 2007). Using confocal microscopy, we then examined whether perisynaptic processes changed with neuronal age. We examined 64 MFT of adult-born neurons at 14, 17, 21, 28 and 56 dpi (5–12 MFT per mouse, 1–2 mice per time point, Fig. 2c, d) and measured the percentage of the projected surface area of the MFT covered by astrocytic processes. On average, 24.6 ± 1.6 % of the surface area of terminals was covered by astrocytic processes. Although the projected area of the MFT increased with neuronal age (Supplementary Fig. 3), the proportion of MFT area covered by astrocytic processes remained constant (Spearman’s Rank correlation test, p = 0.25, R2 = 0.01, Fig. 2d). Thus, perisynaptic processes were present on MFT and their coverage did not depend on MFT size or neuronal age.Fig. 2


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)

Astrocytic perisynaptic processes ensheathe MFT of adult-born neurons. a Electron micrographs of astrocytic processes (false-colored in green) ensheathing synapses between axon terminals of 56 dpi adult-born neurons (red) and dendrites or thorny excrescences of CA3 pyramidal neurons (blue). The perisynaptic ensheathement covers the presynaptic bouton (left panel) or both the presynaptic terminal and the dendrite (right panel). Arrows indicate glycogen granules; arrowheads indicate cytoskeletal filaments. b Three-dimensional reconstruction of a synapse between the dendrite of a CA3 pyramidal neuron (white) and the axon terminal of a newborn neuron (red), ensheathed by an astrocytic process (green). c Confocal micrographs showing contacts between the MFT of a 56 dpi adult-born neuron and astrocytic processes. Left panel maximal intensity projection (after deconvolution). Right panel single focal plane and orthogonal projections. d Distribution of the proportion of the surface of MFT covered by astrocytic processes, as a function of MFT area and neuronal age (Spearman’s Rank correlation test, p = 0.25, R2 = 0.01, n = 5–12 MFT per timepoint). Scale bars in a and b 1 µm, in c 2 µm
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig2: Astrocytic perisynaptic processes ensheathe MFT of adult-born neurons. a Electron micrographs of astrocytic processes (false-colored in green) ensheathing synapses between axon terminals of 56 dpi adult-born neurons (red) and dendrites or thorny excrescences of CA3 pyramidal neurons (blue). The perisynaptic ensheathement covers the presynaptic bouton (left panel) or both the presynaptic terminal and the dendrite (right panel). Arrows indicate glycogen granules; arrowheads indicate cytoskeletal filaments. b Three-dimensional reconstruction of a synapse between the dendrite of a CA3 pyramidal neuron (white) and the axon terminal of a newborn neuron (red), ensheathed by an astrocytic process (green). c Confocal micrographs showing contacts between the MFT of a 56 dpi adult-born neuron and astrocytic processes. Left panel maximal intensity projection (after deconvolution). Right panel single focal plane and orthogonal projections. d Distribution of the proportion of the surface of MFT covered by astrocytic processes, as a function of MFT area and neuronal age (Spearman’s Rank correlation test, p = 0.25, R2 = 0.01, n = 5–12 MFT per timepoint). Scale bars in a and b 1 µm, in c 2 µm
Mentions: Finally, we examined the astrocytic ensheathment on the efferent synapses of the new neurons in the CA3 area, i.e., the mossy fiber terminals (MFT). Using serial-section electron microscopy, we analyzed 27 MFT and found that all but one were ensheathed by astrocytic perisynaptic processes (Fig. 2a, b) that covered either the terminal only (1 of 26 boutons, Fig. 2a left panel) or both the dendrite and the terminal (25 of 26 boutons, Fig. 2a right panel and Fig. 2b). Consistently with previous observations in the CA3, astrocytic processes were tightly apposed to the MFT or the dendritic shaft but never touched thorny excrescences or synaptic clefts, which were engulfed in the MFT (Rollenhagen et al. 2007). Using confocal microscopy, we then examined whether perisynaptic processes changed with neuronal age. We examined 64 MFT of adult-born neurons at 14, 17, 21, 28 and 56 dpi (5–12 MFT per mouse, 1–2 mice per time point, Fig. 2c, d) and measured the percentage of the projected surface area of the MFT covered by astrocytic processes. On average, 24.6 ± 1.6 % of the surface area of terminals was covered by astrocytic processes. Although the projected area of the MFT increased with neuronal age (Supplementary Fig. 3), the proportion of MFT area covered by astrocytic processes remained constant (Spearman’s Rank correlation test, p = 0.25, R2 = 0.01, Fig. 2d). Thus, perisynaptic processes were present on MFT and their coverage did not depend on MFT size or neuronal age.Fig. 2

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