Diversity of layer 5 projection neurons in the mouse motor cortex

Abstract

In the primary motor cortex (M1), layer 5 projection neurons signal directly to distant motor structures to drive movement. Despite their pivotal position and acknowledged diversity these neurons are traditionally separated into broad commissural and corticofugal types, and until now no attempt has been made at resolving the basis for their diversity. We therefore probed the electrophysiological and morphological properties of retrogradely labeled M1 corticospinal (CSp), corticothalamic (CTh), and commissural projecting corticostriatal (CStr) and corticocortical (CC) neurons. An unsupervised cluster analysis established at least four phenotypes with additional differences between lumbar and cervical projecting CSp neurons. Distinguishing parameters included the action potential (AP) waveform, firing behavior, the hyperpolarisation-activated sag potential, sublayer position, and soma and dendrite size. CTh neurons differed from CSp neurons in showing spike frequency acceleration and a greater sag potential. CStr neurons had the lowest AP amplitude and maximum rise rate of all neurons. Temperature influenced spike train behavior in corticofugal neurons. At 26°C CTh neurons fired bursts of APs more often than CSp neurons, but at 36°C both groups fired regular APs. Our findings provide reliable phenotypic fingerprints to identify distinct M1 projection neuron classes as a tool to understand their unique contributions to motor function.

JNK1 controls dendritic field size in L2/3 and L5 of the motor cortex, constrains soma size, and influences fine motor coordination

“…Many of the pyramidal neurons we traced in L5 had large somas consistent with their being corticospinal projecting neurons of L5B (Oswald et al, 2013). Three-dimensional confocal sections underwent Sholl analysis.…”

Instructing Perisomatic Inhibition by Direct Lineage Reprogramming of Neocortical Projection Neurons

“…We next considered whether the observed increase in inhibition could be due to inhibitory input onto distinct regions of PNs (e.g., cell soma, axonal hillock, or dendritic arbor), as CFuPNs differ from CPNs in cell morphology, including larger somata (Larkman and Mason, 1990) and broader apical dendritic tuft arborization (Oswald et al, 2013). …”

Chimeric rabies SADB19-VSVg-pseudotyped lentiviral vectors mediate long-range retrograde transduction from the mouse spinal cord

“…Retrograde labeling using fluorescent dyes has uncovered some of this complexity and allowed both electrophysiological and morphological identification of these subtypes. 24,25 To extend these analyses towards understanding function at the molecular (protein/RNA) level, it will be necessary to develop viruses capable of retrograde transport that can also regulate gene expression. Viral technologies, as described here, combined with overexpression, shRNA-mediated knockdown, optogenetics and the rapidly evolving field of genome editing will enormously expand our capacity for understanding neuronal function at the molecular, physiological and behavioral levels.…”

“…Male Swiss Webster mice (2-3-month old) were used for all injections. Protocols followed those used in Oswald et al 24 Briefly, mice were anaesthetized with 70 mg kg − 1 ketamine, 0.5 mg kg − 1 domitor and given 0.05 mg kg − 1 atropine to reduce lung secretions. Mice were shaved at the lumbar hump and local analgesic (4 mg kg − 1 lignocaine) applied above the incision.…”