Cracking the Function of Layers in the Sensory Cortex

Abstract

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.

Keywords: cortex; cortical layers; cortical microcircuits; inhibitory circuits; neural circuits; neural codes; neural computation; neurotechnology; optogenetics.

Figure 1:. Architectural principles of the cortical layers.

A) Diagram of the major excitatory cell types of the cortical layers, including L4 neurons that project locally, L2/3 and L5 IT (intratelencephalic) neurons that project intracortically, and L5 ‘pyramidal tract’ PT and L6 ‘corticothalamic’ CT neurons that project subcortically. B) Schematic of the ‘feed-forward’ architecture of the neocortex, emphasizing the increase in the specificity of translaminar targets across the layers. L6 circuitry has been excluded for clarity. C) Schematic of the change in the population size of principal cells in each layer (left) and the corresponding sparsity of their population responses to sensory stimuli (right).

Figure 2:. Examples of circuit motifs for basic sensory transformations and computations in L4 and L2/3.

A) Diagram of the thalamocortical circuit that generates orientation selectivity between the visual thalamus and primary visual cortex. Top: structure of receptive fields of the corresponding neurons. B) Diagram of a circuit between L4 and L2/3 that could generate complex cells from simple cells in V1. Top: structure of receptive fields of the corresponding neurons. C) Recurrent excitatory circuitry in L4 that linearly amplifies thalamocortical input. D) A simple feed-forward inhibitory circuit that enforces coincidence detection between thalamus and L4. E) Dimensional expansion of the sensory code between thalamus and cortical L4. F) Diagram of horizontal circuits in L2/3 that might contribute to contextual modulation. G) Schematic of the minimal recurrent excitatory/inhibitory circuit for generating gamma frequency oscillations in L2/3. H) Legend.

Figure 3:. New methods for dissection cortical layer function.

A) Schematic of a mechanical setup for the simultaneous insertion of multiple ultra-high density multielectrode arrays (courtesy of New Scale Technologies). B) Schematic of a multi-layer silicon probe integrating electrodes and optical waveguides for recoding and optogenetics (courtesy of V. Lanzio and S. Cabrini). C) Schematic of a very large field of view high speed volumetric two photon microscope for densely imaging across multiple layers and multiple connected cortical areas simultaneously. D) Schematic of using a holographic multiphoton microscope to selectively perturb individual layers in the same animal on different trials. E) Schematic of a paradigm for mapping the physiological responses of L2/3 and L4 cortical neurons with calcium imaging, and then optogenetically stimulating a precise ensemble of presynaptic L4 neurons while recording from a L2/3 neuron in attempt to recapitulate the sensory response properties of the L2/3 neuron. F) Sequence of proposed experiments for correlating the sensory physiology, synaptic connectivity, and transcriptionally defined cell types of densely imaged cortical neurons across layers.