Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, United States; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States; Department of Statistical Sciences, University of Padova, Padova, Italy; Division of Biostatistics and Epidemiology, Department of Healthcare Policy and Research, Weill Cornell Medicine, New York, United States
David Stafford
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
Benjamin Snyder
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
Andrew Egladyous
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
Desiree Chu
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
Savitha Sridharan
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
Daniel P Mossing
Department of Biophysics, University of California, Berkeley, Berkeley, United States
Liam Paninski
Neurobiology and Behavior Program, Columbia University, New York, United States; Center for Theoretical Neuroscience, Columbia University, New York, United States; Departments of Statistics and Neuroscience, Columbia University, New York, United States; Grossman Center for the Statistics of Mind, Columbia University, New York, United States
John Ngai
Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, United States; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States; QB3 Functional Genomics Laboratory, University of California, Berkeley, Berkeley, United States
Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, United States; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
The neocortex is functionally organized into layers. Layer four receives the densest bottom up sensory inputs, while layers 2/3 and 5 receive top down inputs that may convey predictive information. A subset of cortical somatostatin (SST) neurons, the Martinotti cells, gate top down input by inhibiting the apical dendrites of pyramidal cells in layers 2/3 and 5, but it is unknown whether an analogous inhibitory mechanism controls activity in layer 4. Using high precision circuit mapping, in vivo optogenetic perturbations, and single cell transcriptional profiling, we reveal complementary circuits in the mouse barrel cortex involving genetically distinct SST subtypes that specifically and reciprocally interconnect with excitatory cells in different layers: Martinotti cells connect with layers 2/3 and 5, whereas non-Martinotti cells connect with layer 4. By enforcing layer-specific inhibition, these parallel SST subnetworks could independently regulate the balance between bottom up and top down input.
