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

Abstract

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.

Feedback Controllability is a Normative Theory of Neural Population Dynamics

“…Therefore, it is very likely that the distinct neuron populations underlying feedforward vs. feedback controllability correspond to different classes of excitatory neurons in L5. Indeed, diverse studies in multiple species and brain areas have found that there are two major distinguishable classes of L5 pyramidal neurons: extratelencephalicephalic (ET) and intratelencephalic (IT) [50,51]. Anatomically, ET neurons project to the thalamus, mid-brain, and brainstem, with only modest intra-columnar connectivity.…”

“…Not only do these findings map onto the properties of L5 intra-and extratelencephalic pyramidal neurons, respectively, they intuitively map onto the rotational and amplification dynamics expressed at the population level that we found. Both the non-normality of neural circuits due to Dales law and the distinguishing characteristics of L5 intra-and extratelencephalic neurons are ubiquitous across sensory, cognitive, and motor cortical areas [49,51,50]. As such, there is every reason to believe that similar principles of control will apply throughout cortex.…”

Cadherins orchestrate specific patterns of perisomatic inhibition onto distinct pyramidal cell populations

“…Indeed, mice demonstrate a more adept ability to regulate the activity of ET neurons compared to IT neurons 66 . In contrast, L5 IT cells might compute more diverse information and require increased plasticity 66 CCK+ inputs may confer more precision in the modulation of L5 IT neurons, a phenomenon further reinforced by modulatory pathways 67,68 .…”

Neuromodulatory control of complex adaptive dynamics in the brain

“…Other neuromodulatory classes can instead promote increases in feedback processing. There is evidence to suggest that neuromodulatory neurotransmitters can directly facilitate the interaction between the apical and basal dendritic trees L5 PT pyramidal cells [91][92][93][94]. Hyperpolarization-activated cyclic nucleotide-gated (HCN) Ih channels typically ensure that the apical and basal dendritic compartments of the L5 PT remain electrically isolated from one another [82,95,96].…”