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3 results on '"Alfiler, Lauren"'

1. Morphoelectric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex.

Author

Chartrand T, Dalley R, Close J, Goriounova NA, Lee BR, Mann R, Miller JA, Molnar G, Mukora A, Alfiler L, Baker K, Bakken TE, Berg J, Bertagnolli D, Braun T, Brouner K, Casper T, Csajbok EA, Dee N, Egdorf T, Enstrom R, Galakhova AA, Gary A, Gelfand E, Goldy J, Hadley K, Heistek TS, Hill D, Jorstad N, Kim L, Kocsis AK, Kruse L, Kunst M, Leon G, Long B, Mallory M, McGraw M, McMillen D, Melief EJ, Mihut N, Ng L, Nyhus J, Oláh G, Ozsvár A, Omstead V, Peterfi Z, Pom A, Potekhina L, Rajanbabu R, Rozsa M, Ruiz A, Sandle J, Sunkin SM, Szots I, Tieu M, Toth M, Trinh J, Vargas S, Vumbaco D, Williams G, Wilson J, Yao Z, Barzo P, Cobbs C, Ellenbogen RG, Esposito L, Ferreira M, Gouwens NW, Grannan B, Gwinn RP, Hauptman JS, Jarsky T, Keene CD, Ko AL, Koch C, Ojemann JG, Patel A, Ruzevick J, Silbergeld DL, Smith K, Sorensen SA, Tasic B, Ting JT, Waters J, de Kock CPJ, Mansvelder HD, Tamas G, Zeng H, Kalmbach B, and Lein ES

Subjects
Animals, Humans, Mice, Axons metabolism, Interneurons metabolism, Pyramidal Cells metabolism, Transcriptome, Neocortex cytology, Neocortex metabolism
Abstract

Neocortical layer 1 (L1) is a site of convergence between pyramidal-neuron dendrites and feedback axons where local inhibitory signaling can profoundly shape cortical processing. Evolutionary expansion of human neocortex is marked by distinctive pyramidal neurons with extensive L1 branching, but whether L1 interneurons are similarly diverse is underexplored. Using Patch-seq recordings from human neurosurgical tissue, we identified four transcriptomic subclasses with mouse L1 homologs, along with distinct subtypes and types unmatched in mouse L1. Subclass and subtype comparisons showed stronger transcriptomic differences in human L1 and were correlated with strong morphoelectric variability along dimensions distinct from mouse L1 variability. Accompanied by greater layer thickness and other cytoarchitecture changes, these findings suggest that L1 has diverged in evolution, reflecting the demands of regulating the expanded human neocortical circuit.

Published
2023
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2. Signature morphoelectric properties of diverse GABAergic interneurons in the human neocortex.

Author

Lee BR, Dalley R, Miller JA, Chartrand T, Close J, Mann R, Mukora A, Ng L, Alfiler L, Baker K, Bertagnolli D, Brouner K, Casper T, Csajbok E, Donadio N, Driessens SLW, Egdorf T, Enstrom R, Galakhova AA, Gary A, Gelfand E, Goldy J, Hadley K, Heistek TS, Hill D, Hou WH, Johansen N, Jorstad N, Kim L, Kocsis AK, Kruse L, Kunst M, León G, Long B, Mallory M, Maxwell M, McGraw M, McMillen D, Melief EJ, Molnar G, Mortrud MT, Newman D, Nyhus J, Opitz-Araya X, Ozsvár A, Pham T, Pom A, Potekhina L, Rajanbabu R, Ruiz A, Sunkin SM, Szöts I, Taskin N, Thyagarajan B, Tieu M, Trinh J, Vargas S, Vumbaco D, Waleboer F, Walling-Bell S, Weed N, Williams G, Wilson J, Yao S, Zhou T, Barzó P, Bakken T, Cobbs C, Dee N, Ellenbogen RG, Esposito L, Ferreira M, Gouwens NW, Grannan B, Gwinn RP, Hauptman JS, Hodge R, Jarsky T, Keene CD, Ko AL, Korshoej AR, Levi BP, Meier K, Ojemann JG, Patel A, Ruzevick J, Silbergeld DL, Smith K, Sørensen JC, Waters J, Zeng H, Berg J, Capogna M, Goriounova NA, Kalmbach B, de Kock CPJ, Mansvelder HD, Sorensen SA, Tamas G, Lein ES, and Ting JT

Subjects
Animals, Humans, Mice, Electrophysiological Phenomena, gamma-Aminobutyric Acid metabolism, Patch-Clamp Techniques, GABAergic Neurons metabolism, Interneurons metabolism, Neocortex cytology, Neocortex metabolism
Abstract

Human cortex transcriptomic studies have revealed a hierarchical organization of γ-aminobutyric acid-producing (GABAergic) neurons from subclasses to a high diversity of more granular types. Rapid GABAergic neuron viral genetic labeling plus Patch-seq (patch-clamp electrophysiology plus single-cell RNA sequencing) sampling in human brain slices was used to reliably target and analyze GABAergic neuron subclasses and individual transcriptomic types. This characterization elucidated transitions between PVALB and SST subclasses, revealed morphological heterogeneity within an abundant transcriptomic type, identified multiple spatially distinct types of the primate-specialized double bouquet cells (DBCs), and shed light on cellular differences between homologous mouse and human neocortical GABAergic neuron types. These results highlight the importance of multimodal phenotypic characterization for refinement of emerging transcriptomic cell type taxonomies and for understanding conserved and specialized cellular properties of human brain cell types.

Published
2023
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3. Local connectivity and synaptic dynamics in mouse and human neocortex.

Author

Campagnola L, Seeman SC, Chartrand T, Kim L, Hoggarth A, Gamlin C, Ito S, Trinh J, Davoudian P, Radaelli C, Kim MH, Hage T, Braun T, Alfiler L, Andrade J, Bohn P, Dalley R, Henry A, Kebede S, Alice M, Sandman D, Williams G, Larsen R, Teeter C, Daigle TL, Berry K, Dotson N, Enstrom R, Gorham M, Hupp M, Dingman Lee S, Ngo K, Nicovich PR, Potekhina L, Ransford S, Gary A, Goldy J, McMillen D, Pham T, Tieu M, Siverts L, Walker M, Farrell C, Schroedter M, Slaughterbeck C, Cobb C, Ellenbogen R, Gwinn RP, Keene CD, Ko AL, Ojemann JG, Silbergeld DL, Carey D, Casper T, Crichton K, Clark M, Dee N, Ellingwood L, Gloe J, Kroll M, Sulc J, Tung H, Wadhwani K, Brouner K, Egdorf T, Maxwell M, McGraw M, Pom CA, Ruiz A, Bomben J, Feng D, Hejazinia N, Shi S, Szafer A, Wakeman W, Phillips J, Bernard A, Esposito L, D'Orazi FD, Sunkin S, Smith K, Tasic B, Arkhipov A, Sorensen S, Lein E, Koch C, Murphy G, Zeng H, and Jarsky T

Subjects
Adult, Animals, Datasets as Topic, Excitatory Postsynaptic Potentials, Female, Humans, Inhibitory Postsynaptic Potentials, Male, Mice, Mice, Transgenic, Models, Neurological, Neocortex cytology, Temporal Lobe cytology, Temporal Lobe physiology, Visual Cortex cytology, Visual Cortex physiology, Neocortex physiology, Neural Pathways, Neurons physiology, Synapses physiology, Synaptic Transmission
Abstract

We present a unique, extensive, and open synaptic physiology analysis platform and dataset. Through its application, we reveal principles that relate cell type to synaptic properties and intralaminar circuit organization in the mouse and human cortex. The dynamics of excitatory synapses align with the postsynaptic cell subclass, whereas inhibitory synapse dynamics partly align with presynaptic cell subclass but with considerable overlap. Synaptic properties are heterogeneous in most subclass-to-subclass connections. The two main axes of heterogeneity are strength and variability. Cell subclasses divide along the variability axis, whereas the strength axis accounts for substantial heterogeneity within the subclass. In the human cortex, excitatory-to-excitatory synaptic dynamics are distinct from those in the mouse cortex and vary with depth across layers 2 and 3.

Published
2022
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