Abstract

The structure of brain regions is assumed to correlate with their function, but there are very few instances in which the relationship has been demonstrated in the live brain. This is due to the difficulty of simultaneously measuring functional and structural properties of brain areas, particularly at cellular resolution. Here, we performed label-free, third-harmonic generation (THG) microscopy to obtain a key structural signature of cortical areas, their effective attenuation lengths (EAL), in the vertical columns of functionally defined primary visual cortex and five adjacent visual areas in awake mice. EALs measured by THG microscopy in the cortex and white matter showed remarkable correspondence with the functional retinotopic sign map of each area. Structural features such as cytoarchitecture, myeloarchitecture and blood vessel architecture were correlated with areal EAL values, suggesting that EAL is a function of these structural features as an optical property of these areas. These results demonstrate for the first time a strong relationship between structural substrates of visual cortical areas and their functional representation maps in vivo. This study may also help in understanding the coupling between structure and function in other animal models as well as in humans.

Highlights

  • Form and function are closely related in nature, and an important question in neuroscience is to understand the relationship between the structure and function of brain regions [1]

  • We recently showed that the effective attenuation lengths (EAL) can be estimated either with third-harmonic generation (THG) imaging of blood vessels and myelin fibers at 1300 nm excitation wavelength in the cortex and in the white matter, respectively, or focally ablating tissue at multiple depths in the primary visual cortex (V1) of awake mice [19]

  • We imaged one field of view (FOV) in random locations. Since both lateral and medial visual areas are smaller than V1, our FOV is mostly located around the center of these higher visual areas

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Summary

Introduction

Form and function are closely related in nature, and an important question in neuroscience is to understand the relationship between the structure and function of brain regions [1]. Cytoarchitecture [2], and myeloarchitecture [3,4] are commonly used metrics for defining structural features of the brain. Previous studies have suggested relationships between cytoarchitecture and function [10,11], as well as between myeloarchitecture and function of brain regions [12,13,14] among humans and nonhuman primates. Some of these relationships can be measured by structural and functional magnetic resonance imaging (MRI) [15]. High-resolution imaging technologies which can provide both structural and functional information in small animal model systems in vivo are needed

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