Fast-spiking Parvalbumin Interneurons are Frequently Myelinated in the Cerebral Cortex of Mice and Humans.

J Stedehouder,S A Kushner,J A Slotman,J J Couey,B Hosseini,G Shpak,C M F Dirven,D Brizee,A B Houtsmuller

doi:10.1093/cercor/bhx203

Abstract

Myelination, the insulating ensheathment of axons by oligodendrocytes, is thought to both optimize signal propagation and provide metabolic support. Despite the well-established physiological importance of myelination to neuronal function, relatively little is known about the myelination of GABAergic interneurons in the cerebral cortex. Here, we report that a large fraction of myelin in mouse cerebral cortex ensheaths GABAergic interneurons, reaching up to 80% in hippocampal subregions. Moreover, we find that a very high proportion of neocortical and hippocampal parvalbumin (PV) interneurons exhibit axonal myelination. Using a combination of intracellular recordings and biocytin labeling of ex vivo human neocortex, we also confirm that axons of fast-spiking PV interneurons are extensively myelinated in the human brain. PV interneuron myelination in both mice and humans exhibits a stereotyped topography with a bias towards proximal axonal segments and relatively short internodes (~27 μm) interspersed with branch points. Interestingly, myelin-deficient Shiverer mice exhibit an increased density and more proximal location of en passant boutons, suggesting that myelination might function in part to regulate synapse formation along PV interneuron axons. Taken together, fast-spiking interneuron myelination is likely to have broad implications for cerebral cortex function in health and disease.

Highlights

Myelination is the insulating ensheathment of axons by oligodendrocytes, demonstrated to optimize action potential (AP) propagation and metabolic demands (Lee et al 2012b; Nave and Werner 2014; Saab et al 2016)
To examine the extent to which GABAergic axons are myelinated in the mouse brain, we utilized the Ai14 cre-dependent fluorescence reporter strain in combination with cre driver lines for either PV or somatostatin (SOM) interneuron subclasses, or broadly among GABAergic interneurons (Glutamate Decarboxylase 2, GAD65; GAD2)
We report that a substantial fraction of myelin in the cerebral cortex ensheaths axons of GABAergic interneurons, a finding predominately attributable to the fastspiking PV+ subclass of interneurons

Summary

Introduction

Myelination is the insulating ensheathment of axons by oligodendrocytes, demonstrated to optimize action potential (AP) propagation and metabolic demands (Lee et al 2012b; Nave and Werner 2014; Saab et al 2016). The myelination of pyramidal neurons has been extensively investigated (Tomassy et al 2014), but comparatively little is known about myelination of GABAergic interneurons. Several studies have reported myelination of local GABAergic interneurons throughout the brain (McGee et al 2005; Micheva et al 2016; Stedehouder and Kushner 2017). The ubiquity of cerebral cortex parvalbumin-positive (PV+) interneuron myelination remains largely unexplored in mice, and has rarely been investigated in humans. GABAergic interneurons exert a powerful modulation on local cerebral cortex network activity and brain oscillations. 5002 | Cerebral Cortex, 2017, Vol 27, No 10

Methods

Results

Conclusion