Churchland lab

By Felicia Davatolhagh & Anne Churchland

Today’s paper is Cortical Glutamatergic Projection Neuron Types Contribute to Distinct Functional Subnetworks by Hemanth Mohan, Xu An, Hideki Kondo, Shengli Zhao, Katherine S. Matho, Simon Musall, Partha Mitra, and Z. Josh Huang. In this paper, the authors reveal that pyramidal tract (PT) and intratelencephalic (IT) pyramidal neuron subtypes have distinct neural responses across cortex during different behavioral states and as an animal processes sensory information. 

Approach: The authors recorded large-scale calcium responses of PT and IT neurons across the dorsal cortex using widefield imaging and genetic targeting. Novel mouse driver lines Fezf2 and Plxnd1 were crossed onto an Ai148 reporter line to selectively express GCaMP6f in PT and IT neurons. This combination permitted the authors to monitor neural activity of distinct cell types through the intact cleared skull to understand the differences between PT and IT neural activity. 

Take-home messages: The main message taken from the paper is the observation that PT and IT neurons have distinct activation patterns during various aspects of behavior. The authors find differences during wakeful resting, spontaneous movements, and sensory stimulation (i.e. visual, whisker, and orofacial). Furthermore, they reveal that PT and IT neurons are dynamically tuned to different sensorimotor components of a hand-assisted pellet feeding task. Specifically, these pyramidal subtypes form functional subnetworks with activation patterns spanning distinct regions. PT neurons were activated across parietal and frontal cortex, while IT neurons were activated in orofacial primary sensory cortex (frontolateral posterior node; FLP) and in primary and secondary motor cortex (frontolateral anterior node; FLA). These subnetworks were further dissected using a laser scanning method to bilaterally inhibit regions of the dorsal cortex, finding that parietofrontal and frontolateral subnetworks serve distinct roles in the feeding behavior paradigm.

Skeptics corner: The authors found preferential activation of IT neurons over PT neurons in response to sensory inputs including visual, orofacial and whisking. This was surprising to us since given our observations of sensory-locked responses in both PT and IT neurons (Musall et al. 2022). It is important to note that a direct comparison of these figures is difficult since ΔF/F is used in Mohan et al, while the figure in Musall et al shows the output of an encoding model. Another potential contributor to this difference in findings may be the use of dissimilar sensory modalities (somatosensory vs. auditory) or behavioral state (passive vs. engaged in a task). Nonetheless, this raises interesting questions about the circumstances under which PT neurons are modulated by sensory signals.