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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

Schematic illustration of the formation of astrocytic perisynaptic processes on spines or MFT from adult–born neurons. a Dendritic spines: as a spine from a new neuron extends from its dendrite (gray), it touches several potential presynaptic partners (pink, left panel). Upon reaching its target axon terminal (blue, middle panel), the spine forms a multiple-synapse bouton. The perisynaptic process that was present on the pre-existing synapse modifies its structure to ensheathe the newly formed spine (green, right panel). b MFT: as a MFT from a newborn neuron (gray) extends, it generally contacts a dendrite (red) already synapsing with one or several other MFT (blue). The perisynaptic process (green) that was present on the pre-existing synapse modifies its structure to ensheathe the newly formed MFT
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Fig6: Schematic illustration of the formation of astrocytic perisynaptic processes on spines or MFT from adult–born neurons. a Dendritic spines: as a spine from a new neuron extends from its dendrite (gray), it touches several potential presynaptic partners (pink, left panel). Upon reaching its target axon terminal (blue, middle panel), the spine forms a multiple-synapse bouton. The perisynaptic process that was present on the pre-existing synapse modifies its structure to ensheathe the newly formed spine (green, right panel). b MFT: as a MFT from a newborn neuron (gray) extends, it generally contacts a dendrite (red) already synapsing with one or several other MFT (blue). The perisynaptic process (green) that was present on the pre-existing synapse modifies its structure to ensheathe the newly formed MFT

Mentions: The relatively small number of astrocytes generated during adulthood suggests that adult-born neurons are principally contacted by pre-existing astrocytes. We, however, do not exclude that some perisynaptic processes may be formed by astrocytes generated during adulthood, prior to the observed newborn neurons. Furthermore, the observation of perisynaptic processes on MSB indicates that pre-existing perisynaptic processes modify their structure to ensheath nascent spines from adult-born neurons, as schematized in Fig. 6. Thus, these observations suggest that pre-existing perisynaptic processes are highly plastic and modulate their structure to establish contact with the nascent spines or boutons of adult-born neurons. These results are consistent with the notion that astrocytes remain plastic throughout adulthood. Indeed, previous reports have shown that astrocytic processes are very plastic and their motility is coordinated with the motility of dendritic spines (Nishida and Okabe 2007; Haber et al. 2006; Hirrlinger et al. 2004; Witcher et al. 2007). Astrocytes extend and retract processes towards nascent dendritic spines in the course of minutes and, interestingly, glial processes are more stable on larger spines, suggesting that they may contribute to spine maturation (Haber et al. 2006). Indeed, when analyzing the motility of astrocytic processes and of their adjacent dendritic spines, Nishida et al. found that astrocytic contact enhanced the lifetime and maturation of nascent dendritic spines (Nishida and Okabe 2007). Also, astrocytes are able to increase their ensheathement of excitatory synapses on dendritic spines during a period of modified neuronal activity in the adult mouse, indicating that their structural plasticity is regulated by neuronal activity (Hirrlinger et al. 2004; Genoud et al. 2006). Further experiments using live-imaging approaches on adult-born neurons and astrocytic processes may determine whether the growth of astrocytic processes precedes or follows the growth and stabilization of dendritic spines of adult-born neurons and to what extent these contacts are necessary for the stable integration of new neurons. However, in view of these studies, we predict that the structural plasticity of astrocytes is necessary to enable the proper integration of adult-born neurons in the hippocampal network and a dysregulation of pre-existing glia may impair the synaptic integration of new neurons in the adult hippocampus. Consistently, the expression of a mutated form of GFAP in the astroglial compartment reduced adult neurogenesis and impaired the development of adult-born neurons in a mouse model of Alexander’s disease (Hagemann et al. 2013).Fig. 6


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)

Schematic illustration of the formation of astrocytic perisynaptic processes on spines or MFT from adult–born neurons. a Dendritic spines: as a spine from a new neuron extends from its dendrite (gray), it touches several potential presynaptic partners (pink, left panel). Upon reaching its target axon terminal (blue, middle panel), the spine forms a multiple-synapse bouton. The perisynaptic process that was present on the pre-existing synapse modifies its structure to ensheathe the newly formed spine (green, right panel). b MFT: as a MFT from a newborn neuron (gray) extends, it generally contacts a dendrite (red) already synapsing with one or several other MFT (blue). The perisynaptic process (green) that was present on the pre-existing synapse modifies its structure to ensheathe the newly formed MFT
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig6: Schematic illustration of the formation of astrocytic perisynaptic processes on spines or MFT from adult–born neurons. a Dendritic spines: as a spine from a new neuron extends from its dendrite (gray), it touches several potential presynaptic partners (pink, left panel). Upon reaching its target axon terminal (blue, middle panel), the spine forms a multiple-synapse bouton. The perisynaptic process that was present on the pre-existing synapse modifies its structure to ensheathe the newly formed spine (green, right panel). b MFT: as a MFT from a newborn neuron (gray) extends, it generally contacts a dendrite (red) already synapsing with one or several other MFT (blue). The perisynaptic process (green) that was present on the pre-existing synapse modifies its structure to ensheathe the newly formed MFT
Mentions: The relatively small number of astrocytes generated during adulthood suggests that adult-born neurons are principally contacted by pre-existing astrocytes. We, however, do not exclude that some perisynaptic processes may be formed by astrocytes generated during adulthood, prior to the observed newborn neurons. Furthermore, the observation of perisynaptic processes on MSB indicates that pre-existing perisynaptic processes modify their structure to ensheath nascent spines from adult-born neurons, as schematized in Fig. 6. Thus, these observations suggest that pre-existing perisynaptic processes are highly plastic and modulate their structure to establish contact with the nascent spines or boutons of adult-born neurons. These results are consistent with the notion that astrocytes remain plastic throughout adulthood. Indeed, previous reports have shown that astrocytic processes are very plastic and their motility is coordinated with the motility of dendritic spines (Nishida and Okabe 2007; Haber et al. 2006; Hirrlinger et al. 2004; Witcher et al. 2007). Astrocytes extend and retract processes towards nascent dendritic spines in the course of minutes and, interestingly, glial processes are more stable on larger spines, suggesting that they may contribute to spine maturation (Haber et al. 2006). Indeed, when analyzing the motility of astrocytic processes and of their adjacent dendritic spines, Nishida et al. found that astrocytic contact enhanced the lifetime and maturation of nascent dendritic spines (Nishida and Okabe 2007). Also, astrocytes are able to increase their ensheathement of excitatory synapses on dendritic spines during a period of modified neuronal activity in the adult mouse, indicating that their structural plasticity is regulated by neuronal activity (Hirrlinger et al. 2004; Genoud et al. 2006). Further experiments using live-imaging approaches on adult-born neurons and astrocytic processes may determine whether the growth of astrocytic processes precedes or follows the growth and stabilization of dendritic spines of adult-born neurons and to what extent these contacts are necessary for the stable integration of new neurons. However, in view of these studies, we predict that the structural plasticity of astrocytes is necessary to enable the proper integration of adult-born neurons in the hippocampal network and a dysregulation of pre-existing glia may impair the synaptic integration of new neurons in the adult hippocampus. Consistently, the expression of a mutated form of GFAP in the astroglial compartment reduced adult neurogenesis and impaired the development of adult-born neurons in a mouse model of Alexander’s disease (Hagemann et al. 2013).Fig. 6

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