Specialized Subpopulations of Deep-Layer Pyramidal Neurons in the Neocortex: Bridging Cellular Properties to Functional Consequences

Abstract

Neocortical pyramidal neurons with somata in layers 5 and 6 are among the most visually striking and enigmatic neurons in the brain. These deep-layer pyramidal neurons (DLPNs) integrate a plethora of cortical and extracortical synaptic inputs along their impressive dendritic arbors. The pattern of cortical output to both local and long-distance targets is sculpted by the unique physiological properties of specific DLPN subpopulations. Here we revisit two broad DLPN subpopulations: those that send their axons within the telencephalon (intratelencephalic neurons) and those that project to additional target areas outside the telencephalon (extratelencephalic neurons). While neuroscientists across many subdisciplines have characterized the intrinsic and synaptic physiological properties of DLPN subpopulations, our increasing ability to selectively target and manipulate these output neuron subtypes advances our understanding of their distinct functional contributions. This Viewpoints article summarizes our current knowledge about DLPNs and highlights recent work elucidating the functional differences between DLPN subpopulations.

Figure 1.

Diversity in characteristic properties of DLPNs in rodent cortex. Whereas ET (blue) and IT (red) projection neurons are found throughout the infragranular layers, distinct subtypes of these projection neurons are found in L5 versus L6. Subtypes of ET and IT projection neurons display diversity in sublaminar localization, dendritic morphology, long-range projection target, and characteristic gene expression. Different DLPN types are characterized by a particular apical dendritic morphology or sublaminar somatic position, but there is extensive variability in these features within each class of DLPNs. For example, L5 IT neurons can possess extensive apical tufts or can be tuftless. Also shown here are the brain regions to which each DLPN sends long-range axonal projections; these projections can be ipsilateral (i), contralateral (c), or bilateral (b). However, not all neurons belonging to a DLPN type project to each brain region listed. For example, single L5 ETs may project to only a couple of the brain regions listed. Finally, a few of potentially many characteristic molecular markers of each DLPN type are listed (Voelker et al., 2004; Arlotta et al., 2005; Yoneshima et al., 2006; Molyneaux et al., 2009; Fame et al., 2011; Costa and Müller, 2014; Sorensen et al., 2015). Notably, not every neuron belonging to a DLPN type expresses each gene, and there is substantial overlap in the expression of these molecular markers between DLPN subtypes.

Figure 2.

Functional implications of DLPNs. In vivo interrogations of DLPN in various cortical regions have begun to link different DLPNs to distinct function. For example, in visual cortex, L5 PT neurons participate in visual processing of movement and display broad orientation tuning, whereas L5 IT neurons are involved in high-resolution visual acuity. L6 CT neurons control the gain of the output of the cortical circuit. In motor cortex, L5 IT and PT neurons play distinct roles in guiding movement. IT neurons distribute information related to movement planning to other cortical regions and basal ganglia. IT neurons linking cortical hemispheres through the corpus callosum maintain robustness through redundancy. Thalamus-projecting PT neurons are involved in motor planning via the thalamo-cortical loop. Brainstem-projecting PT neurons send command signals to initiate contralateral movements. Additionally, in auditory cortex, L6 IT neurons participate in multimodal integration and L5 ET neurons in learning-induced plasticity of sound localization. Reconstructed pyramidal neurons from Mieko Morishima, or from www.NeuroMorpho.Org. IDs: 12606-MV-2p (CT), 126012-MV-2f (corticocortical).