Limits...
Dynamic development of the first synapse impinging on adult-born neurons in the olfactory bulb circuit.

Katagiri H, Pallotto M, Nissant A, Murray K, Sassoè-Pognetto M, Lledo PM - Neural Syst Circuits (2011)

Bottom Line: We found that both the ratio of N-methyl-D-aspartate receptor (NMDAR) to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), and the number of functional release sites at proximal inputs reached a maximum during the critical period for the sensory-dependent survival of newborn cells, well before the completion of dendritic arborization.Interestingly, the latter morphological changes disappeared in more mature newly-formed neurons, when the NMDAR to AMPAR ratio had decreased and functional presynaptic terminals expressed only single release sites.Together, these findings show that the first glutamatergic inputs to adult-generated OB interneurons undergo a unique sequence of maturation stages.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory for Perception and Memory, Institut Pasteur, Paris, France. pmlledo@pasteur.fr.

ABSTRACT
The olfactory bulb (OB) receives and integrates newborn interneurons throughout life. This process is important for the proper functioning of the OB circuit and consequently, for the sense of smell. Although we know how these new interneurons are produced, the way in which they integrate into the pre-existing ongoing circuits remains poorly documented. Bearing in mind that glutamatergic inputs onto local OB interneurons are crucial for adjusting the level of bulbar inhibition, it is important to characterize when and how these inputs from excitatory synapses develop on newborn OB interneurons. We studied early synaptic events that lead to the formation and maturation of the first glutamatergic synapses on adult-born granule cells (GCs), the most abundant subtype of OB interneuron. Patch-clamp recordings and electron microscopy (EM) analysis were performed on adult-born interneurons shortly after their arrival in the adult OB circuits. We found that both the ratio of N-methyl-D-aspartate receptor (NMDAR) to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), and the number of functional release sites at proximal inputs reached a maximum during the critical period for the sensory-dependent survival of newborn cells, well before the completion of dendritic arborization. EM analysis showed an accompanying change in postsynaptic density shape during the same period of time. Interestingly, the latter morphological changes disappeared in more mature newly-formed neurons, when the NMDAR to AMPAR ratio had decreased and functional presynaptic terminals expressed only single release sites. Together, these findings show that the first glutamatergic inputs to adult-generated OB interneurons undergo a unique sequence of maturation stages.

No MeSH data available.


Related in: MedlinePlus

Presynaptic properties of synapses contacting developing and mature GCs. (A) Typical responses to paired-pulse stimulation delivered at the proximal site. Top: Mean responses for the whole dataset (all successes and failures). Middle: Mean potency values for responses to the first and second rounds of stimulation (successful responses only). Bottom: AMPAR-mediated EPSC amplitude and potency. AMPAR-mediated EPSC amplitude for responses to the second round of stimulation, after AMPAR-mediated EPSCs amplitude to first stimulation was scaled (black) to potency for AMPAR-mediated EPSCs amplitude (gray). Scale bar = 10 ms and 10 pA. (B) Paired-pulse ratios for successful responses (left) (ten slices, six mice) and AMPAR-mediated EPSC amplitude (right), recorded from mature GCs (10 slices, six mice). (C) Left: Potency ratio (successful responses only) plotted as a function of AMPAR-mediated EPSCs amplitude ratio (successes and failures) recorded from mature GCs. Most points fell on or near the horizontal dashed line. The linear regression line fitted to all data points is shown in black. P < 0.05 indicates significant deviation of the slope from zero. Right: Comparison between observed (exp) Yes and predicted (Poisson) potency ratios. Predicted values were obtained using a Poisson model. Data were for mature GCs. (D) Ratio of AMPAR-mediated to NMDAR-mediated EPSC amplitude increased during the early developmental stage (class 3 versus class 4, class 4 versus mature; *P < 0.05) (class 3: six slices, six mice; class 4: nine slices, eight mice; class 5: four slices, four mice; mature: six slices, five mice).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3278389&req=5

Figure 7: Presynaptic properties of synapses contacting developing and mature GCs. (A) Typical responses to paired-pulse stimulation delivered at the proximal site. Top: Mean responses for the whole dataset (all successes and failures). Middle: Mean potency values for responses to the first and second rounds of stimulation (successful responses only). Bottom: AMPAR-mediated EPSC amplitude and potency. AMPAR-mediated EPSC amplitude for responses to the second round of stimulation, after AMPAR-mediated EPSCs amplitude to first stimulation was scaled (black) to potency for AMPAR-mediated EPSCs amplitude (gray). Scale bar = 10 ms and 10 pA. (B) Paired-pulse ratios for successful responses (left) (ten slices, six mice) and AMPAR-mediated EPSC amplitude (right), recorded from mature GCs (10 slices, six mice). (C) Left: Potency ratio (successful responses only) plotted as a function of AMPAR-mediated EPSCs amplitude ratio (successes and failures) recorded from mature GCs. Most points fell on or near the horizontal dashed line. The linear regression line fitted to all data points is shown in black. P < 0.05 indicates significant deviation of the slope from zero. Right: Comparison between observed (exp) Yes and predicted (Poisson) potency ratios. Predicted values were obtained using a Poisson model. Data were for mature GCs. (D) Ratio of AMPAR-mediated to NMDAR-mediated EPSC amplitude increased during the early developmental stage (class 3 versus class 4, class 4 versus mature; *P < 0.05) (class 3: six slices, six mice; class 4: nine slices, eight mice; class 5: four slices, four mice; mature: six slices, five mice).

Mentions: We also examined the electrophysiological properties of class 5 cells at later time points after viral injection. At about 14 dpi, newborn class 5 GCs exhibit long-term potentiation (LTP) at proximal glutamatergic synapses, but this plasticity disappears over time [26]. Thus, the properties of the input synapses on fully mature GCs may differ from those of synapses on class 5 cells. To examine this possibility, two consecutive stimuli of minimal intensity were delivered to evoke neurotransmitter release from presynaptic terminals contacting mature non-GFP-labeled GCs (Figure 7A). The success rate of the second response exceeded that of the first (a ratio of 1.45 ± 0.17) (Figure 7B). Paired-pulse stimulation also resulted in the facilitation of the mean AMPAR-mediated current amplitude in pre-existing mature GCs (a ratio of 1.33 ± 0.15) (Figure 7A). Neither the success rate ratio nor the paired-pulse ratio differed between developing and mature GCs. The predicted potency ratio was significantly greater than the observed ratio in mature GCs (Figure 7C). Consistent with this result, the linear regression line that fitted data obtained from mature GCs was almost parallel to the horizontal line (slope 0.09 ± 0.15) (Figure 7C). The predicted potency ratio by a simple Poisson release model was also significantly greater than the measured ratio for mature GCs (P < 0.03). Similar to the findings for class 3 cells, these results indicate that mature GCs receive proximal synapses characterized by a single functional release site.


Dynamic development of the first synapse impinging on adult-born neurons in the olfactory bulb circuit.

Katagiri H, Pallotto M, Nissant A, Murray K, Sassoè-Pognetto M, Lledo PM - Neural Syst Circuits (2011)

Presynaptic properties of synapses contacting developing and mature GCs. (A) Typical responses to paired-pulse stimulation delivered at the proximal site. Top: Mean responses for the whole dataset (all successes and failures). Middle: Mean potency values for responses to the first and second rounds of stimulation (successful responses only). Bottom: AMPAR-mediated EPSC amplitude and potency. AMPAR-mediated EPSC amplitude for responses to the second round of stimulation, after AMPAR-mediated EPSCs amplitude to first stimulation was scaled (black) to potency for AMPAR-mediated EPSCs amplitude (gray). Scale bar = 10 ms and 10 pA. (B) Paired-pulse ratios for successful responses (left) (ten slices, six mice) and AMPAR-mediated EPSC amplitude (right), recorded from mature GCs (10 slices, six mice). (C) Left: Potency ratio (successful responses only) plotted as a function of AMPAR-mediated EPSCs amplitude ratio (successes and failures) recorded from mature GCs. Most points fell on or near the horizontal dashed line. The linear regression line fitted to all data points is shown in black. P < 0.05 indicates significant deviation of the slope from zero. Right: Comparison between observed (exp) Yes and predicted (Poisson) potency ratios. Predicted values were obtained using a Poisson model. Data were for mature GCs. (D) Ratio of AMPAR-mediated to NMDAR-mediated EPSC amplitude increased during the early developmental stage (class 3 versus class 4, class 4 versus mature; *P < 0.05) (class 3: six slices, six mice; class 4: nine slices, eight mice; class 5: four slices, four mice; mature: six slices, five mice).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3278389&req=5

Figure 7: Presynaptic properties of synapses contacting developing and mature GCs. (A) Typical responses to paired-pulse stimulation delivered at the proximal site. Top: Mean responses for the whole dataset (all successes and failures). Middle: Mean potency values for responses to the first and second rounds of stimulation (successful responses only). Bottom: AMPAR-mediated EPSC amplitude and potency. AMPAR-mediated EPSC amplitude for responses to the second round of stimulation, after AMPAR-mediated EPSCs amplitude to first stimulation was scaled (black) to potency for AMPAR-mediated EPSCs amplitude (gray). Scale bar = 10 ms and 10 pA. (B) Paired-pulse ratios for successful responses (left) (ten slices, six mice) and AMPAR-mediated EPSC amplitude (right), recorded from mature GCs (10 slices, six mice). (C) Left: Potency ratio (successful responses only) plotted as a function of AMPAR-mediated EPSCs amplitude ratio (successes and failures) recorded from mature GCs. Most points fell on or near the horizontal dashed line. The linear regression line fitted to all data points is shown in black. P < 0.05 indicates significant deviation of the slope from zero. Right: Comparison between observed (exp) Yes and predicted (Poisson) potency ratios. Predicted values were obtained using a Poisson model. Data were for mature GCs. (D) Ratio of AMPAR-mediated to NMDAR-mediated EPSC amplitude increased during the early developmental stage (class 3 versus class 4, class 4 versus mature; *P < 0.05) (class 3: six slices, six mice; class 4: nine slices, eight mice; class 5: four slices, four mice; mature: six slices, five mice).
Mentions: We also examined the electrophysiological properties of class 5 cells at later time points after viral injection. At about 14 dpi, newborn class 5 GCs exhibit long-term potentiation (LTP) at proximal glutamatergic synapses, but this plasticity disappears over time [26]. Thus, the properties of the input synapses on fully mature GCs may differ from those of synapses on class 5 cells. To examine this possibility, two consecutive stimuli of minimal intensity were delivered to evoke neurotransmitter release from presynaptic terminals contacting mature non-GFP-labeled GCs (Figure 7A). The success rate of the second response exceeded that of the first (a ratio of 1.45 ± 0.17) (Figure 7B). Paired-pulse stimulation also resulted in the facilitation of the mean AMPAR-mediated current amplitude in pre-existing mature GCs (a ratio of 1.33 ± 0.15) (Figure 7A). Neither the success rate ratio nor the paired-pulse ratio differed between developing and mature GCs. The predicted potency ratio was significantly greater than the observed ratio in mature GCs (Figure 7C). Consistent with this result, the linear regression line that fitted data obtained from mature GCs was almost parallel to the horizontal line (slope 0.09 ± 0.15) (Figure 7C). The predicted potency ratio by a simple Poisson release model was also significantly greater than the measured ratio for mature GCs (P < 0.03). Similar to the findings for class 3 cells, these results indicate that mature GCs receive proximal synapses characterized by a single functional release site.

Bottom Line: We found that both the ratio of N-methyl-D-aspartate receptor (NMDAR) to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), and the number of functional release sites at proximal inputs reached a maximum during the critical period for the sensory-dependent survival of newborn cells, well before the completion of dendritic arborization.Interestingly, the latter morphological changes disappeared in more mature newly-formed neurons, when the NMDAR to AMPAR ratio had decreased and functional presynaptic terminals expressed only single release sites.Together, these findings show that the first glutamatergic inputs to adult-generated OB interneurons undergo a unique sequence of maturation stages.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory for Perception and Memory, Institut Pasteur, Paris, France. pmlledo@pasteur.fr.

ABSTRACT
The olfactory bulb (OB) receives and integrates newborn interneurons throughout life. This process is important for the proper functioning of the OB circuit and consequently, for the sense of smell. Although we know how these new interneurons are produced, the way in which they integrate into the pre-existing ongoing circuits remains poorly documented. Bearing in mind that glutamatergic inputs onto local OB interneurons are crucial for adjusting the level of bulbar inhibition, it is important to characterize when and how these inputs from excitatory synapses develop on newborn OB interneurons. We studied early synaptic events that lead to the formation and maturation of the first glutamatergic synapses on adult-born granule cells (GCs), the most abundant subtype of OB interneuron. Patch-clamp recordings and electron microscopy (EM) analysis were performed on adult-born interneurons shortly after their arrival in the adult OB circuits. We found that both the ratio of N-methyl-D-aspartate receptor (NMDAR) to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), and the number of functional release sites at proximal inputs reached a maximum during the critical period for the sensory-dependent survival of newborn cells, well before the completion of dendritic arborization. EM analysis showed an accompanying change in postsynaptic density shape during the same period of time. Interestingly, the latter morphological changes disappeared in more mature newly-formed neurons, when the NMDAR to AMPAR ratio had decreased and functional presynaptic terminals expressed only single release sites. Together, these findings show that the first glutamatergic inputs to adult-generated OB interneurons undergo a unique sequence of maturation stages.

No MeSH data available.


Related in: MedlinePlus