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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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A highly specific microcircuit forms among sister excitatory neurons in ontogenetic radial clones(a–d) Quadruple recording of sister excitatory neurons in individual ontogenetic radial clones located in layer 4 & layer 5/6 (a, b) or layer 2/3 & layer 4 (c, d), and their adjacent non-sister excitatory neurons. See Fig. 3 legend for details. (e, f) Summary of the direction of synaptic connections observed between sister excitatory neurons in individual ontogenetic radial clones. The size of the arrows in f reflects the abundance of the connection.
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Figure 4: A highly specific microcircuit forms among sister excitatory neurons in ontogenetic radial clones(a–d) Quadruple recording of sister excitatory neurons in individual ontogenetic radial clones located in layer 4 & layer 5/6 (a, b) or layer 2/3 & layer 4 (c, d), and their adjacent non-sister excitatory neurons. See Fig. 3 legend for details. (e, f) Summary of the direction of synaptic connections observed between sister excitatory neurons in individual ontogenetic radial clones. The size of the arrows in f reflects the abundance of the connection.

Mentions: Previous studies have revealed the overall organization of the excitatory neuron microcircuit in the mature neocortex 28, 29. Thalamic input enters primarily into layer 4 (the first station of sensory processing). Layer 4 excitatory neurons send ascending projections to pyramidal neurons in layer 2/3 (the second station of columnar processing), which provide a prevalent descending projection to layer 5/6 pyramidal neurons (the third station of columnar processing). Descending and ascending excitatory connections also exist between layer 4 and layer 5/6. In addition to the sister neurons radially situated in layer 2/3 and layer 5/6 (Fig. 3 a–g), our dataset of quadruple recordings contained radially aligned sister neurons located in layer 4 and layer 5/6 (Fig. 4 a and b, and Supplementary Fig. S5a) as well as in layer 2/3 and layer 4 (Fig. 4 c and d, and Supplementary Fig. S5b). These experiments allowed us to address the interlaminar direction preference of synaptic connectivity formed within ontogenetic radial clones of excitatory neurons. We found that 15 out of 21 connected sister excitatory neuron pairs located in layer 2/3 and layer 5/6, and 10 out of 14 pairs of those located in layer 4 and layer 5/6 formed synapses in the descending direction (i.e. from layer 2/3 to layer 5/6 and from layer 4 to layer 5/6), whereas 15 out of 19 pairs of connected sister excitatory neurons located in layer 2/3 and layer 4 formed synapses in the ascending direction (i.e. from layer 4 to layer 2/3, Fig. 4 e and f). These results suggest that the synaptic connection formed among sister excitatory neurons in ontogenetic radial clones is rather specific. Moreover, these results demonstrate that the specificity of synaptic connectivity formed within ontogenetic radial clones of excitatory neurons in the developing neocortex is highly similar to that in the mature neocortex.


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

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

A highly specific microcircuit forms among sister excitatory neurons in ontogenetic radial clones(a–d) Quadruple recording of sister excitatory neurons in individual ontogenetic radial clones located in layer 4 & layer 5/6 (a, b) or layer 2/3 & layer 4 (c, d), and their adjacent non-sister excitatory neurons. See Fig. 3 legend for details. (e, f) Summary of the direction of synaptic connections observed between sister excitatory neurons in individual ontogenetic radial clones. The size of the arrows in f reflects the abundance of the connection.
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Related In: Results  -  Collection

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Figure 4: A highly specific microcircuit forms among sister excitatory neurons in ontogenetic radial clones(a–d) Quadruple recording of sister excitatory neurons in individual ontogenetic radial clones located in layer 4 & layer 5/6 (a, b) or layer 2/3 & layer 4 (c, d), and their adjacent non-sister excitatory neurons. See Fig. 3 legend for details. (e, f) Summary of the direction of synaptic connections observed between sister excitatory neurons in individual ontogenetic radial clones. The size of the arrows in f reflects the abundance of the connection.
Mentions: Previous studies have revealed the overall organization of the excitatory neuron microcircuit in the mature neocortex 28, 29. Thalamic input enters primarily into layer 4 (the first station of sensory processing). Layer 4 excitatory neurons send ascending projections to pyramidal neurons in layer 2/3 (the second station of columnar processing), which provide a prevalent descending projection to layer 5/6 pyramidal neurons (the third station of columnar processing). Descending and ascending excitatory connections also exist between layer 4 and layer 5/6. In addition to the sister neurons radially situated in layer 2/3 and layer 5/6 (Fig. 3 a–g), our dataset of quadruple recordings contained radially aligned sister neurons located in layer 4 and layer 5/6 (Fig. 4 a and b, and Supplementary Fig. S5a) as well as in layer 2/3 and layer 4 (Fig. 4 c and d, and Supplementary Fig. S5b). These experiments allowed us to address the interlaminar direction preference of synaptic connectivity formed within ontogenetic radial clones of excitatory neurons. We found that 15 out of 21 connected sister excitatory neuron pairs located in layer 2/3 and layer 5/6, and 10 out of 14 pairs of those located in layer 4 and layer 5/6 formed synapses in the descending direction (i.e. from layer 2/3 to layer 5/6 and from layer 4 to layer 5/6), whereas 15 out of 19 pairs of connected sister excitatory neurons located in layer 2/3 and layer 4 formed synapses in the ascending direction (i.e. from layer 4 to layer 2/3, Fig. 4 e and f). These results suggest that the synaptic connection formed among sister excitatory neurons in ontogenetic radial clones is rather specific. Moreover, these results demonstrate that the specificity of synaptic connectivity formed within ontogenetic radial clones of excitatory neurons in the developing neocortex is highly similar to that in the mature neocortex.

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.

Show MeSH