White Matter Interstitial Neurons in the Adult Human Brain: 3% of Cortical Neurons in Quest for Recognition.

Goran Sedmak,Miloš Judaš

doi:10.3390/cells10010190

Abstract

White matter interstitial neurons (WMIN) are a subset of cortical neurons located in the subcortical white matter. Although they were fist described over 150 years ago, they are still largely unexplored and often considered a small, functionally insignificant neuronal population. WMIN are adult remnants of neurons located in the transient fetal subplate zone (SP). Following development, some of the SP neurons undergo apoptosis, and the remaining neurons are incorporated in the adult white matter as WMIN. In the adult human brain, WMIN are quite a large population of neurons comprising at least 3% of all cortical neurons (between 600 and 1100 million neurons). They include many of the morphological neuronal types that can be found in the overlying cerebral cortex. Furthermore, the phenotypic and molecular diversity of WMIN is similar to that of the overlying cortical neurons, expressing many glutamatergic and GABAergic biomarkers. WMIN are often considered a functionally unimportant subset of neurons. However, upon closer inspection of the scientific literature, it has been shown that WMIN are integrated in the cortical circuitry and that they exhibit diverse electrophysiological properties, send and receive axons from the cortex, and have active synaptic contacts. Based on these data, we are able to enumerate some of the potential WMIN roles, such as the control of the cerebral blood flow, sleep regulation, and the control of information flow through the cerebral cortex. Also, there is a number of studies indicating the involvement of WMIN in the pathophysiology of many brain disorders such as epilepsy, schizophrenia, Alzheimer’s disease, etc. All of these data indicate that WMIN are a large population with an important function in the adult brain. Further investigation of WMIN could provide us with novel data crucial for an improved elucidation of the pathophysiology of many brain disorders. In this review, we provide an overview of the current WMIN literature, with an emphasis on studies conducted on the human brain.

Highlights

The human brain is composed of billions of molecularly, structurally, and functionally distinct neurons
We provide an overview of the current white matter interstitial neurons (WMIN) literature, with an emphasis on studies conducted on the human brain
In all species analyzed to date, WMIN are present throughout the entire subcortical white matter [3,6,9,13,15,16,17,19,21,29,30,31,32]

Summary

Introduction

The human brain is composed of billions of molecularly, structurally, and functionally distinct neurons. In all species analyzed to date, WMIN are present throughout the entire subcortical white matter [3,6,9,13,15,16,17,19,21,29,30,31,32] They display morphological and molecular heterogeneity almost equal to that of cortical neurons in the remaining six cortical layers and include both pyramidal and non-pyramidal types [9,16,17,18,33] (Figure 1). The quantitative studies of the number of WMIN have been significantly influenced by three factors: (a) the assumption that the majority of subplate neurons undergo apoptosis; (b) the assumption that the surviving WMIN represent a pathological finding; and (c) existing problems with a proper delineation of WMIN-containing compartments These issues have contributed to the persistence of the notion that WMIN are a rather small neuronal population in the human brain, probably significant only in pathological cases. The part of the white matter which should represent the “WMIN compartment” has been defined in significantly different ways, leading to significantly different WMIN counts (for details, see [32])

Illustration

Functional Importance of WMIN

Pathology of WMIN

Findings

Conclusions