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Specific synapses develop preferentially among sister excitatory neurons in the neocortex.

Yu YC, Bultje RS, Wang X, Shi SH - Nature (2009)

Bottom Line: We found that radially aligned sister excitatory neurons have a propensity for developing unidirectional chemical synapses with each other rather than with neighbouring non-siblings.Moreover, these synaptic connections display the same interlaminar directional preference as those observed in the mature neocortex.These results indicate that specific microcircuits develop preferentially within ontogenetic radial clones of excitatory neurons in the developing neocortex and contribute to the emergence of functional columnar microarchitectures in the mature neocortex.

View Article: PubMed Central - PubMed

Affiliation: Developmental Biology Program, Memorial Sloan Kettering Cancer Centre, 1275 York Avenue, USA.

ABSTRACT
Neurons in the mammalian neocortex are organized into functional columns. Within a column, highly specific synaptic connections are formed to ensure that similar physiological properties are shared by neuron ensembles spanning from the pia to the white matter. Recent studies indicate that synaptic connectivity in the neocortex is sparse and highly specific to allow even adjacent neurons to convey information independently. How this fine-scale microcircuit is constructed to create a functional columnar architecture at the level of individual neurons largely remains a mystery. Here we investigate whether radial clones of excitatory neurons arising from the same mother cell in the developing neocortex serve as a substrate for the formation of this highly specific microcircuit. We labelled ontogenetic radial clones of excitatory neurons in the mouse neocortex by in utero intraventricular injection of enhanced green fluorescent protein (EGFP)-expressing retroviruses around the onset of the peak phase of neocortical neurogenesis. Multiple-electrode whole-cell recordings were performed to probe synapse formation among these EGFP-labelled sister excitatory neurons in radial clones and the adjacent non-siblings during postnatal stages. We found that radially aligned sister excitatory neurons have a propensity for developing unidirectional chemical synapses with each other rather than with neighbouring non-siblings. Moreover, these synaptic connections display the same interlaminar directional preference as those observed in the mature neocortex. These results indicate that specific microcircuits develop preferentially within ontogenetic radial clones of excitatory neurons in the developing neocortex and contribute to the emergence of functional columnar microarchitectures in the mature neocortex.

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Synapse formation between sister excitatory neurons in ontogenetic radial clones(a) Images of a pair of EGFP-expressing (green, middle) sister neurons in a radial clone in whole-cell configuration. Alexa 546-conjugated biocytin (red, right) was included in the recording pipette to confirm the cells being recorded and to reveal cell morphology. DIC image is shown to the left and arrows indicate two EGFP-expressing green sister neurons. Scale bars: 100 µm and 50 µm. (b, c) Sample traces of action potentials triggered in the presynaptic neurons (red) and EPSCs (b) or EPSPs (c) recorded in the postsynaptic neurons under voltage-clamp (b) or current-clamp (c) mode (green or black). The bold traces represent the average and the grey traces represent the individual recordings. Scale bars: 40 mV, 15 pA, and 200 msec (b); 50 mV, 1.5 mV, and 50 msec (c). (d) EPSC-blockage in postsynaptic neuron 2 by NBQX and D-AP5, but not by picrotoxin. Scale bar: 10 pA and 5 msec. (e) Summary of the rate of connectivity between sister excitatory neuron pairs in individual radial clones.
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Figure 2: Synapse formation between sister excitatory neurons in ontogenetic radial clones(a) Images of a pair of EGFP-expressing (green, middle) sister neurons in a radial clone in whole-cell configuration. Alexa 546-conjugated biocytin (red, right) was included in the recording pipette to confirm the cells being recorded and to reveal cell morphology. DIC image is shown to the left and arrows indicate two EGFP-expressing green sister neurons. Scale bars: 100 µm and 50 µm. (b, c) Sample traces of action potentials triggered in the presynaptic neurons (red) and EPSCs (b) or EPSPs (c) recorded in the postsynaptic neurons under voltage-clamp (b) or current-clamp (c) mode (green or black). The bold traces represent the average and the grey traces represent the individual recordings. Scale bars: 40 mV, 15 pA, and 200 msec (b); 50 mV, 1.5 mV, and 50 msec (c). (d) EPSC-blockage in postsynaptic neuron 2 by NBQX and D-AP5, but not by picrotoxin. Scale bar: 10 pA and 5 msec. (e) Summary of the rate of connectivity between sister excitatory neuron pairs in individual radial clones.

Mentions: Synapse formation is a key step in the functional development of neurons in the brain. To assess synapses formed onto the excitatory neurons in ontogenetic radial clones, we examined the spontaneous miniature excitatory postsynaptic currents (mini-EPSCs) (Supplementary Fig. S2 e–k). While the mean amplitude of mini-EPSCs detected at different developmental stages remained similar (Supplementary Fig. S2 e and f), the frequency increased drastically as development progressed (Supplementary Fig. S2 e and g). Moreover, the rise and decay of mini-EPSCs speeded up significantly with development (Fig. 2 h–k). These results suggest progressive formation and maturation of synapses onto the excitatory neurons in ontogenetic radial clones during postnatal development.


Specific synapses develop preferentially among sister excitatory neurons in the neocortex.

Yu YC, Bultje RS, Wang X, Shi SH - Nature (2009)

Synapse formation between sister excitatory neurons in ontogenetic radial clones(a) Images of a pair of EGFP-expressing (green, middle) sister neurons in a radial clone in whole-cell configuration. Alexa 546-conjugated biocytin (red, right) was included in the recording pipette to confirm the cells being recorded and to reveal cell morphology. DIC image is shown to the left and arrows indicate two EGFP-expressing green sister neurons. Scale bars: 100 µm and 50 µm. (b, c) Sample traces of action potentials triggered in the presynaptic neurons (red) and EPSCs (b) or EPSPs (c) recorded in the postsynaptic neurons under voltage-clamp (b) or current-clamp (c) mode (green or black). The bold traces represent the average and the grey traces represent the individual recordings. Scale bars: 40 mV, 15 pA, and 200 msec (b); 50 mV, 1.5 mV, and 50 msec (c). (d) EPSC-blockage in postsynaptic neuron 2 by NBQX and D-AP5, but not by picrotoxin. Scale bar: 10 pA and 5 msec. (e) Summary of the rate of connectivity between sister excitatory neuron pairs in individual radial clones.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2727717&req=5

Figure 2: Synapse formation between sister excitatory neurons in ontogenetic radial clones(a) Images of a pair of EGFP-expressing (green, middle) sister neurons in a radial clone in whole-cell configuration. Alexa 546-conjugated biocytin (red, right) was included in the recording pipette to confirm the cells being recorded and to reveal cell morphology. DIC image is shown to the left and arrows indicate two EGFP-expressing green sister neurons. Scale bars: 100 µm and 50 µm. (b, c) Sample traces of action potentials triggered in the presynaptic neurons (red) and EPSCs (b) or EPSPs (c) recorded in the postsynaptic neurons under voltage-clamp (b) or current-clamp (c) mode (green or black). The bold traces represent the average and the grey traces represent the individual recordings. Scale bars: 40 mV, 15 pA, and 200 msec (b); 50 mV, 1.5 mV, and 50 msec (c). (d) EPSC-blockage in postsynaptic neuron 2 by NBQX and D-AP5, but not by picrotoxin. Scale bar: 10 pA and 5 msec. (e) Summary of the rate of connectivity between sister excitatory neuron pairs in individual radial clones.
Mentions: Synapse formation is a key step in the functional development of neurons in the brain. To assess synapses formed onto the excitatory neurons in ontogenetic radial clones, we examined the spontaneous miniature excitatory postsynaptic currents (mini-EPSCs) (Supplementary Fig. S2 e–k). While the mean amplitude of mini-EPSCs detected at different developmental stages remained similar (Supplementary Fig. S2 e and f), the frequency increased drastically as development progressed (Supplementary Fig. S2 e and g). Moreover, the rise and decay of mini-EPSCs speeded up significantly with development (Fig. 2 h–k). These results suggest progressive formation and maturation of synapses onto the excitatory neurons in ontogenetic radial clones during postnatal development.

Bottom Line: We found that radially aligned sister excitatory neurons have a propensity for developing unidirectional chemical synapses with each other rather than with neighbouring non-siblings.Moreover, these synaptic connections display the same interlaminar directional preference as those observed in the mature neocortex.These results indicate that specific microcircuits develop preferentially within ontogenetic radial clones of excitatory neurons in the developing neocortex and contribute to the emergence of functional columnar microarchitectures in the mature neocortex.

View Article: PubMed Central - PubMed

Affiliation: Developmental Biology Program, Memorial Sloan Kettering Cancer Centre, 1275 York Avenue, USA.

ABSTRACT
Neurons in the mammalian neocortex are organized into functional columns. Within a column, highly specific synaptic connections are formed to ensure that similar physiological properties are shared by neuron ensembles spanning from the pia to the white matter. Recent studies indicate that synaptic connectivity in the neocortex is sparse and highly specific to allow even adjacent neurons to convey information independently. How this fine-scale microcircuit is constructed to create a functional columnar architecture at the level of individual neurons largely remains a mystery. Here we investigate whether radial clones of excitatory neurons arising from the same mother cell in the developing neocortex serve as a substrate for the formation of this highly specific microcircuit. We labelled ontogenetic radial clones of excitatory neurons in the mouse neocortex by in utero intraventricular injection of enhanced green fluorescent protein (EGFP)-expressing retroviruses around the onset of the peak phase of neocortical neurogenesis. Multiple-electrode whole-cell recordings were performed to probe synapse formation among these EGFP-labelled sister excitatory neurons in radial clones and the adjacent non-siblings during postnatal stages. We found that radially aligned sister excitatory neurons have a propensity for developing unidirectional chemical synapses with each other rather than with neighbouring non-siblings. Moreover, these synaptic connections display the same interlaminar directional preference as those observed in the mature neocortex. These results indicate that specific microcircuits develop preferentially within ontogenetic radial clones of excitatory neurons in the developing neocortex and contribute to the emergence of functional columnar microarchitectures in the mature neocortex.

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