Extended Data Fig. 4: Morphology of Patch-seq and EM cells grouped by subclass or Sst MET-type.

Morphology of Patch-seq (before vertical line) and EM cells (after vertical line, including from the columnar sample and curated MCs) grouped by subclass or Sst MET-type. Abbreviations above cells indicate target cell type (described in Extended Data Fig. 2). Perisomatic targeting cells (PTC), distal dendrite targeting cells (DTC), sparsely targeting cells (STC), and inhibitory targeting cells (ITC). The number indicates the frequency with which that cell was predicted to that MET-type. For Sst MET-types, at least one EM cell is predicted to belong to 11 of 13 Sst MET-types. Sst MET-types: Sst MET-1, -2, -5, and -7 contain only a few EM neurons, but visual inspection demonstrates that morphologies are quite similar between Patch-seq cells and EM; these neurons are largely distal targeting cells (DTCs), consistent with the Sst subclass prediction. Sst MET-3 EM column neurons (n = 15) are found in L2/3 and L4 and largely have DTC connectivity profiles (11/15 cells). These cells have one longer, descending dendrite, and a “fanning” axonal profile that widens in L1 and L2/3. Sst MET-4 EM column and curated neurons (n = 11) have somas in L5, and dominant L1 axon. All column cells (6/6 cells) are also DTCs. Sst MET-6 EM column and curated neurons (n = 9) have somas in deep L5 and a “T-shaped” axonal profile. Six of seven column neurons are DTCs. Sst MET-8 column and curated neurons (n = 12) have somas in L4 and upper L5 and dominant L4 axon. Five out of ten column neurons have an Sst-consistent, DTC label. All of these neurons, like the Patch-seq neurons in this type, have axon in L1. Neurons that map to other connection types lack axon in L1. Sst MET-9 column and curated neurons (n = 6) have somas in upper L5 or L6 and large dendritic trees. Four of the five column neurons are DTCs. Sst MET-10 column neurons (n = 4) have somas in upper L5 or L6 and large dendritic trees with dominant axon in L5 and/or L6. Half of the cells are DTCs with axons that extend to superficial layers, but not necessarily to L1. Sst MET-12 column neurons (n = 12) have somas in L6. Most cells have large dendritic trees and diverse axonal phenotypes. EM DTCs that map to this type lack L1-projections and are thus non-Martinotti cells (3/12). EM PTCs also frequently map to Sst MET-types that are dominated by non-Martinotti neurons (5/12 cells are PTCs). Lamp5 subclass: Patch-seq Lamp5 neurons most characteristically have small dendrites and a wide, dense, horizontally extending axon in L1. All L1 EM cells (9/9) have small dendrites and the sparse targeting cell (STC) profile that is suggested to correspond to Lamp5/neurogliaform cells (NGCs). Lamp5 neurons found in deeper layers also have dense axon overlapping with their dendrites, but it’s distributed across layers. Only 7/21 deep Lamp5 cells are STCs. Pvalb subclass: Patch-seq Pvalb neurons have typical Pvalb/basket cell morphologies with stellate dendrites and abundant local axon in each cell’s soma layer. Most cells extend axon across multiple layers, but avoid L1. Thirty of 37 EM column cells are proximal targeting cells (PTCs). Scng subclass: Patch-seq Scng neurons have widely branching bitufted or multipolar dendrites and axons. EM column cells that map to this type (n = 4) each have a different connectivity type. Vip subclass: Patch-seq Vip neurons frequently have bipolar primary dendrites and axon with a narrow horizontal and long vertical extent. Twenty out of 22 EM column cells that map to Vip have an inhibitory cell targeting type (ITCs), which is consistent with Vip neurons. Figure adapted with permission from ref. ¹⁶, Cell Press.