Neocortical layer 5 subclasses: From cellular properties to roles in behavior

Layer 5 (L5) serves as the main output layer of cortical structures, where long-range projecting pyramidal neurons broadcast the columnar output to other cortical and extracortical regions of the brain. L5 pyramidal neurons are grouped into two subclasses based on their projection targets; while intratelencephalic (IT) neurons project to cortical areas and the striatum, extratelencephalic (ET) neurons project to subcortical areas such as the thalamus, midbrain, and brainstem. Each L5 subclass possesses distinct morphological and electrophysiological properties and is incorporated into a unique synaptic network. Thanks to recent advances in genetic tools and methodologies, it has now become possible to distinguish between the two subclasses in the living brain. There is increasing evidence indicating that each subclass plays a unique role in sensory processing, decision-making, and learning. This review first summarizes the anatomical and physiological properties as well as the neuromodulation of IT and ET neurons in the rodent neocortex, and then reviews recent literature on their roles in sensory processing and rodent behavior. Our ultimate goal is to provide a comprehensive understanding of the role of each subclass in cortical function by examining their operational regimes based on their cellular properties.