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Scholarly Works (4 results)

  • Article
  • Peer Reviewed
UC Berkeley Previously Published Works (2018)
Understanding how cortical activity generates sensory perceptions requires a detailed dissection of the function of cortical layers. Despite our relatively extensive knowledge of their anatomy and wiring, we have a limited grasp of what each layer contributes to cortical computation. We need to develop a theory of cortical function that is rooted solidly in each layer's component cell types and fine circuit architecture and produces predictions that can be validated by specific perturbations. Here we briefly review the progress toward such a theory and suggest an experimental road map toward this goal. We discuss new methods for the all-optical interrogation of cortical layers, for correlating in vivo function with precise identification of transcriptional cell type, and for mapping local and long-range activity in vivo with synaptic resolution. The new technologies that can crack the function of cortical layers are finally on the immediate horizon.
    Cover page: Cracking the Function of Layers in the Sensory Cortex
    • Thesis
    • Peer Reviewed
    UC Berkeley Electronic Theses and Dissertations (2018)

    Understanding how the canonical circuit implements computations requires that we characterize the components of the circuit and determine how they interact. Cortical components are often equated to the various classes of excitatory and inhibitory neuronal cell-types that occupy the six cortical layers. Excitatory cortical neurons are known to exhibit stereotyped, cell-type specific patterns of connectivity; these excitatory synaptic pathways are a central feature of cortical organization. It has been less clear whether inhibitory neurons are organized according to a similar logic. In this thesis I describe my efforts to map the inhibitory pathways of the neocortex, using the mouse primary somatosensory barrel cortex as a model.

    In Chapter 1, I will give an introduction to theories of cortical function and general overview of the organization of cortical circuits. I will also provide a focused review of the inhibitory circuitry in layer 5 of the cortex. This chapter is presented, in part, in the form of reproductions of material from two reviews (one published and one in preparation) that I co-authored with my advisor. In Chapter 2, I describe the discovery of a novel disynaptic inhibitory pathway between layer 4 and layer 5 of the somatosensory cortex, and present evidence that this pathway contributes to selective sensory representations in layer 5. This work is presented as a published manuscript, which I co-authored with Dr. Scott Pluta. In Chapter 3, I describe a series of experiments probing the organization of two subnetworks of dendrite-targeting interneurons. These subnetworks exhibit complementary patterns of connectivity which enable them to differentially modulate the dynamics of cortical activity in a layer-specific manner. This work is presented as a first author manuscript (currently in review). Finally, in Chapter 4 I offer closing thoughts and directions for future work.

      Cover page: Inhibitory pathways in the neocortical microcircuit
      • Article
      • Peer Reviewed
      UC Berkeley Previously Published Works (2019)
      The descending microcircuit from layer 2/3 (L2/3) to layer 5 (L5) is one of the strongest excitatory pathways in the cortex, presumably forming a core component of its feedforward hierarchy. To date, however, no experiments have selectively tested the impact of L2/3 activity on L5 during active sensation. We used optogenetic, cell-type-specific manipulation of L2/3 neurons in the barrel cortex of actively sensing mice (of either sex) to elucidate the significance of this pathway to sensory coding in L5. Contrary to standard models, activating L2/3 predominantly suppressed spontaneous activity in L5, whereas deactivating L2/3 mainly facilitated touch responses in L5. Somatostatin interneurons are likely important to this suppression because their optogenetic deactivation significantly altered the functional impact of L2/3 onto L5. The net effect of L2/3 was to enhance the stimulus selectivity and expand the range of L5 output. These data imply that the core cortical pathway increases the selectivity and expands the range of cortical output through feedforward inhibition.SIGNIFICANCE STATEMENT The primary sensory cortex contains six distinct layers that interact to form the basis of our perception. While rudimentary patterns of connectivity between the layers have been outlined quite extensively in vitro, functional relationships in vivo, particularly during active sensation, remain poorly understood. We used cell-type-specific optogenetics to test the functional relationship between layer 2/3 and layer 5. Surprisingly, we discovered that L2/3 primarily suppresses cortical output from L5. The recruitment of somatostatin-positive interneurons is likely fundamental to this relationship. The net effect of this translaminar suppression is to enhance the selectivity and expand the range of receptive fields, therefore potentially sharpening the perception of space.
        Cover page: Superficial Layers Suppress the Deep Layers to Fine-tune Cortical Coding
        • Article
        • Peer Reviewed
        UC Berkeley Previously Published Works (2019)
        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.
          Cover page: Complementary networks of cortical somatostatin interneurons enforce layer specific control
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