Dataset Information

Cell type composition and circuit organization of clonally related excitatory neurons in the juvenile mouse neocortex.

ABSTRACT: Clones of excitatory neurons derived from a common progenitor have been proposed to serve as elementary information processing modules in the neocortex. To characterize the cell types and circuit diagram of clonally related excitatory neurons, we performed multi-cell patch clamp recordings and Patch-seq on neurons derived from Nestin-positive progenitors labeled by tamoxifen induction at embryonic day 10.5. The resulting clones are derived from two radial glia on average, span cortical layers 2-6, and are composed of a random sampling of transcriptomic cell types. We find an interaction between shared lineage and connection type: related neurons are more likely to be connected vertically across cortical layers, but not laterally within the same layer. These findings challenge the view that related neurons show uniformly increased connectivity and suggest that integration of vertical intra-clonal input with lateral inter-clonal input may represent a developmentally programmed connectivity motif supporting the emergence of functional circuits.

SUBMITTER: Cadwell CR

PROVIDER: S-EPMC7162653 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Cell type composition and circuit organization of clonally related excitatory neurons in the juvenile mouse neocortex.

Cadwell Cathryn R CR Scala Federico F Fahey Paul G PG Kobak Dmitry D Mulherkar Shalaka S Sinz Fabian H FH Papadopoulos Stelios S Tan Zheng H ZH Johnsson Per P Hartmanis Leonard L Li Shuang S Cotton Ronald J RJ Tolias Kimberley F KF Sandberg Rickard R Berens Philipp P Jiang Xiaolong X Tolias Andreas Savas AS

eLife 20200305

Clones of excitatory neurons derived from a common progenitor have been proposed to serve as elementary information processing modules in the neocortex. To characterize the cell types and circuit diagram of clonally related excitatory neurons, we performed multi-cell patch clamp recordings and Patch-seq on neurons derived from <i>Nestin</i>-positive progenitors labeled by tamoxifen induction at embryonic day 10.5. The resulting clones are derived from two radial glia on average, span cortical la ...[more]

PMID: 32134385

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Project description:A key feature of excitatory synapses is the existence of subsynaptic protein nanoclusters whose precise alignment across the cleft in a trans-synaptic nanocolumn influences the strength of synaptic transmission. However, whether nanocolumn properties vary between excitatory synapses functioning in different cellular contexts is unknown. We used a combination of confocal and DNA-PAINT super-resolution microscopy to directly compare the organization of shared scaffold proteins at two important excitatory synapses - those forming onto excitatory principal neurons (Ex→Ex synapses) and those forming onto parvalbumin-expressing interneurons (Ex→PV synapses). As in Ex→Ex synapses, we find that in Ex→PV synapses presynaptic Munc13-1 and postsynaptic PSD-95 both form nanoclusters that demonstrate alignment, underscoring synaptic nanostructure and the trans-synaptic nanocolumn as conserved organizational principles of excitatory synapses. Despite the general conservation of these features, we observed specific differences in the characteristics of pre- and postsynaptic Ex→PV nanostructure. Ex→PV synapses contained larger PSDs with fewer PSD-95 NCs when accounting for size than Ex→Ex synapses. Furthermore, the PSD-95 NCs were larger and denser. The identity of the postsynaptic cell also had a retrograde impact on Munc13-1 organization, as Ex→PV synapses hosted larger Munc13-1 puncta that contained less dense but larger and more numerous Munc13-1 NCs. Moreover, we measured the spatial variability of transsynaptic alignment in these synapse types, revealing protein alignment in Ex→PV synapses over a distinct range of distances compared to Ex→Ex synapses. We conclude that while general principles of nanostructure and alignment are shared, cell-specific elements of nanodomain organization likely contribute to functional diversity of excitatory synapses. Understanding the rules of synapse nanodomain assembly, which themselves are cell-type specific, will be essential for illuminating brain network dynamics.

Dataset Information

Cell type composition and circuit organization of clonally related excitatory neurons in the juvenile mouse neocortex.

Publications

Cell type composition and circuit organization of clonally related excitatory neurons in the juvenile mouse neocortex.

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