Defining area-specific cellular and circuit-level specialization in the human temporal cortex - Project Summary / Abstract The ability to rapidly and accurately recognize objects is a core function of the primate visual system. Extensive theoretical, behavioral, and invasive neurophysiological studies in nonhuman primates have revealed key neuroanatomical substrates and computational mechanisms involved object recognition. Object recognition is primarily carried out in the ventral visual processing stream, which is composed of multiple, hierarchically organized cortical areas originating in the primary visual cortex and culminating the in anterior portion of the inferior temporal lobe, where neurons encode specific object identities irrespective of size, position, and pose. In parallel, there has been a revolution in our understanding of neuronal diversity, with dozens of unique molecular cell types identified in the primate cerebral cortex. High-throughput single-cell genomics studies across multiple species have demonstrated that, while inhibitory interneurons are similar regardless of cortical area, excitatory neurons in different cortical areas have slightly different transcriptomic profiles. Multimodal studies in mice have further revealed that even between primary sensory regions, the morphoelectric properties and local connectivity of conserved cell types can differ. However, little is known about how cortical neurons and local circuits are uniquely specialized in the primate inferior temporal cortex to carry out object identification. The goal of this project is to identify area-specific cellular and circuit-level features that distinguish the human inferior temporal cortex from other cortical areas. Leveraging our access to fresh human brain tissue, we have identified electrophysiological and synaptic features that are unique to upper-layer excitatory neurons in the human inferior temporal gyrus. Here, we will build on these findings and test the hypothesis that excitatory neurons in the human inferior temporal cortex are uniquely specialized to carry out object recognition computations. In Aim 1, we will perform multimodal profiling of single-neuron morphology, electrophysiology and gene expression using Patch-seq to examine intrinsic biophysical properties, spontaneous activity, plasticity, response to neuromodulators, and detailed axodendritic morphology of neuron. Using the transcriptomic information obtained from each neuron, we will identify the specific molecular cell types and genes involved. In Aim 2, we will perform barcoded rabies virus circuit mapping in organotypic slices to identify cell type–specific, local connectivity motifs that may play an important role in local computations enabling rapid computation of object identity in the inferior temporal cortex. These data will provide fundamental insights into the neurobiological mechanisms underlying visual object recognition in the human inferior temporal cortex and, more broadly, on the extent to which excitatory cortical neurons in the human cerebral cortex are specialized to perform unique computations in functionally different cortical areas. Ultimately, a more mechanistic understanding of area-specific neuronal physiology and local circuit connectivity can potentially inform biologically realistic models to improve the speed and accuracy of computer vision platforms performing object recognition tasks.
