Abstract
Advances in brain connectomics set the need for detailed knowledge of functional properties of myelinated and non-myelinated (if present) axons in specific white matter pathways. The corpus callosum (CC), a major white matter structure interconnecting brain hemispheres, is extensively used for studying CNS axonal function. Unlike another widely used CNS white matter preparation, the optic nerve where all axons are myelinated, the CC contains also a large population of non-myelinated axons, making it particularly useful for studying both types of axons. Electrophysiological studies of optic nerve use suction electrodes on nerve ends to stimulate and record compound action potentials (CAPs) that adequately represent its axonal population, whereas CC studies use microelectrodes (MEs), recording from a limited area within the CC. Here we introduce a novel robust isolated "whole" CC preparation comparable to optic nerve. Unlike ME recordings where the CC CAP peaks representing myelinated and non-myelinated axons vary broadly in size, "whole" CC CAPs show stable reproducible ratios of these two main peaks, and also reveal a third peak, suggesting a distinct group of smaller caliber non-myelinated axons. We provide detailed characterization of "whole" CC CAPs and conduction velocities of myelinated and non-myelinated axons along the rostro-caudal axis of CC body and show advantages of this preparation for comparing axonal function in wild type and dysmyelinated shiverer mice, studying the effects of temperature dependence, bath-applied drugs and ischemia modeled by oxygen-glucose deprivation. Due to the isolation from gray matter, our approach allows for studying CC axonal function without possible "contamination" by reverberating signals from gray matter. Our analysis of "whole" CC CAPs revealed higher complexity of myelinated and non-myelinated axonal populations, not noticed earlier. This preparation may have a broad range of applications as a robust model for studying myelinated and non-myelinated axons of the CNS in various experimental models.
Highlights
White matter comprises nearly half of brain volume and contains important axonal pathways interconnecting different parts of the brain
In ME recordings, the relative sizes of peaks N1 and N2 vary broadly depending on positioning of the ME tip, while suction electrode (SE)-recorded "whole" corpus callosum (CC) Compound action potential (CAP) are devoid of this bias
Because longer conduction distances allow for better separation of CAP components by their arrival times in this paper we focused on "whole" CC CAPs recorded at 4 mm conduction distance, with symmetrically positioned stimulating and recording SE’s
Summary
White matter comprises nearly half of brain volume and contains important axonal pathways interconnecting different parts of the brain. Recent advances in brain connectomics [1,2,3,4,5,6,7] provided detailed knowledge on structural framework of brain wiring, while the functional properties of axons in many white matter pathways remain less explored. This applies to conduction properties of axons that define the precise timing of signal delivery that is important for coordinated activity of CNS networks. An important advantage of studying the CC is that, unlike another widely studied white matter structure, the optic nerve [34,35,36,37,38,39,40], where virtually all axons are myelinated, the CC contains myelinated and a large population of non-myelinated axons [10,27,41]
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