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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.


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Astrocytic modulation of glutamatergic synaptic transmission on adult-born neurons. a, b Representative experiment showing whole-cell recordings obtained from a retrovirally labeled 4-week-old neuron. Paired pulses (50 ms apart) were delivered to the perforant path at low frequency (0.07 Hz) in the presence of picrotoxin (100 µM). a Postsynaptic current traces obtained before (Baseline, at 4 min), during (DHK, at 17 min) and after (Wash, at 32 min) application of DHK (300 µM). Each trace is an average of 12 sweeps. Scalebars 100 pA, 20 ms. b Peak amplitude of the first EPSC and paired-pulse ratio (PPR) measured in the same experiment shown in a. Dotted lines denote mean baseline values. c Mean values obtained from nine experiments showing normalized peak EPSCs and PPR. Data points were binned in 1-min intervals. Dots indicate mean ± SEM values. DHK reduced peak EPSC amplitude (0.64 ± 0.06, p < 0.01, Wilcoxon test for paired samples). PPR increase was consistent but not significant (1.33 ± 0.26, p = 0.16, Wilcoxon test for paired samples). Gray bars denote DHK (300 µM) application
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Fig4: Astrocytic modulation of glutamatergic synaptic transmission on adult-born neurons. a, b Representative experiment showing whole-cell recordings obtained from a retrovirally labeled 4-week-old neuron. Paired pulses (50 ms apart) were delivered to the perforant path at low frequency (0.07 Hz) in the presence of picrotoxin (100 µM). a Postsynaptic current traces obtained before (Baseline, at 4 min), during (DHK, at 17 min) and after (Wash, at 32 min) application of DHK (300 µM). Each trace is an average of 12 sweeps. Scalebars 100 pA, 20 ms. b Peak amplitude of the first EPSC and paired-pulse ratio (PPR) measured in the same experiment shown in a. Dotted lines denote mean baseline values. c Mean values obtained from nine experiments showing normalized peak EPSCs and PPR. Data points were binned in 1-min intervals. Dots indicate mean ± SEM values. DHK reduced peak EPSC amplitude (0.64 ± 0.06, p < 0.01, Wilcoxon test for paired samples). PPR increase was consistent but not significant (1.33 ± 0.26, p = 0.16, Wilcoxon test for paired samples). Gray bars denote DHK (300 µM) application

Mentions: It is conceivable that the observed physical interactions between perisynaptic astrocytic processes and nascent synapses play both structural and functional roles in the synaptic connectivity of newborn neurons. For instance, it is well known that astrocytic glutamate transporters exert a tight control of glutamate clearance at the synapse (Huang and Bergles 2004). Perisynaptic glutamate uptake can shape the strength and kinetics of postsynaptic currents, which in turn determines the responsiveness to incoming inputs (Oliet et al. 2001). To test whether synaptic transmission onto newborn neurons is also modulated in this fashion, the effect of dihydrokainate (DHK, 300 µM), a specific blocker of the astrocytic glutamate transporter GLT-1 (Oliet et al. 2001; Zhang et al. 2009), was tested on evoked postsynaptic responses. We recorded EPSCs from retrovirally labeled granule cells, at 30 dpi, in response to paired pulses delivered to the perforant path (Laplagne et al. 2006). DHK elicited a significant reduction in the EPSC amplitude that was accompanied by an increase in paired pulse ratio (PPR, Fig. 4). The enhanced paired pulse ratio indicates that presynaptic release probability has been reduced by DHK. Thus, astrocytic glutamate transporters enhance release probability and, as a consequence, strengthen excitatory synaptic transmission onto newly generated granule cells.Fig. 4


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 modulation of glutamatergic synaptic transmission on adult-born neurons. a, b Representative experiment showing whole-cell recordings obtained from a retrovirally labeled 4-week-old neuron. Paired pulses (50 ms apart) were delivered to the perforant path at low frequency (0.07 Hz) in the presence of picrotoxin (100 µM). a Postsynaptic current traces obtained before (Baseline, at 4 min), during (DHK, at 17 min) and after (Wash, at 32 min) application of DHK (300 µM). Each trace is an average of 12 sweeps. Scalebars 100 pA, 20 ms. b Peak amplitude of the first EPSC and paired-pulse ratio (PPR) measured in the same experiment shown in a. Dotted lines denote mean baseline values. c Mean values obtained from nine experiments showing normalized peak EPSCs and PPR. Data points were binned in 1-min intervals. Dots indicate mean ± SEM values. DHK reduced peak EPSC amplitude (0.64 ± 0.06, p < 0.01, Wilcoxon test for paired samples). PPR increase was consistent but not significant (1.33 ± 0.26, p = 0.16, Wilcoxon test for paired samples). Gray bars denote DHK (300 µM) application
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Related In: Results  -  Collection

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Fig4: Astrocytic modulation of glutamatergic synaptic transmission on adult-born neurons. a, b Representative experiment showing whole-cell recordings obtained from a retrovirally labeled 4-week-old neuron. Paired pulses (50 ms apart) were delivered to the perforant path at low frequency (0.07 Hz) in the presence of picrotoxin (100 µM). a Postsynaptic current traces obtained before (Baseline, at 4 min), during (DHK, at 17 min) and after (Wash, at 32 min) application of DHK (300 µM). Each trace is an average of 12 sweeps. Scalebars 100 pA, 20 ms. b Peak amplitude of the first EPSC and paired-pulse ratio (PPR) measured in the same experiment shown in a. Dotted lines denote mean baseline values. c Mean values obtained from nine experiments showing normalized peak EPSCs and PPR. Data points were binned in 1-min intervals. Dots indicate mean ± SEM values. DHK reduced peak EPSC amplitude (0.64 ± 0.06, p < 0.01, Wilcoxon test for paired samples). PPR increase was consistent but not significant (1.33 ± 0.26, p = 0.16, Wilcoxon test for paired samples). Gray bars denote DHK (300 µM) application
Mentions: It is conceivable that the observed physical interactions between perisynaptic astrocytic processes and nascent synapses play both structural and functional roles in the synaptic connectivity of newborn neurons. For instance, it is well known that astrocytic glutamate transporters exert a tight control of glutamate clearance at the synapse (Huang and Bergles 2004). Perisynaptic glutamate uptake can shape the strength and kinetics of postsynaptic currents, which in turn determines the responsiveness to incoming inputs (Oliet et al. 2001). To test whether synaptic transmission onto newborn neurons is also modulated in this fashion, the effect of dihydrokainate (DHK, 300 µM), a specific blocker of the astrocytic glutamate transporter GLT-1 (Oliet et al. 2001; Zhang et al. 2009), was tested on evoked postsynaptic responses. We recorded EPSCs from retrovirally labeled granule cells, at 30 dpi, in response to paired pulses delivered to the perforant path (Laplagne et al. 2006). DHK elicited a significant reduction in the EPSC amplitude that was accompanied by an increase in paired pulse ratio (PPR, Fig. 4). The enhanced paired pulse ratio indicates that presynaptic release probability has been reduced by DHK. Thus, astrocytic glutamate transporters enhance release probability and, as a consequence, strengthen excitatory synaptic transmission onto newly generated granule cells.Fig. 4

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