Ultrastructural heterogeneity of human layer 4 excitatory synaptic boutons in the adult temporal lobe neocortex

Abstract

28Synapses are fundamental building blocks that control and modulate the 'behavior' of brain networks. How 29 their structural composition, most notably their quantitative morphology underlies their computational 30properties remains rather unclear, particularly in humans. Here, excitatory synaptic boutons (SBs) in layer 31 4 (L4) of the temporal lobe neocortex (TLN) were quantitatively investigated. 32Biopsies from epilepsy surgery were used for fine-scale and tomographic electron microscopy to 33 generate 3D-reconstructions of SBs. Particularly, the size of active zones (AZs) and of the three functionally 34 defined pools of synaptic vesicles (SVs) were quantified. 35SBs were comparably small (~2.50 μm 2 ), with a single AZ (~0.13 µm 2 ) and preferentially established on 36 spines. SBs had a total pool of ~1800SVs with strikingly large readily releasable (~ 20), recycling (~ 80) 37 and resting pools (~850). 38Thus, human L4 SBs may act as 'amplifiers' of signals from the sensory periphery and integrate, 39 synchronize and modulate intra-and extra-cortical synaptic activity. 40 41 Introduction 42The neocortex of various animal species including non-human primates (NHPs) and humans is characterized 43 by its six-layered structure, the organization into vertical oriented functional slabs so-called cortical columns 44and a system of long-range horizontal axonal collaterals that connect neurons in the same (intra-laminar) 45 and in different (trans-laminar) cortical layers of a given brain area but also with trans-regional projections 46 to different brain regions (reviewed by Rockland and De Felipe 2018). 47The human TLN representing ~17% of the total volume of the neocortex (Kiernan 2012) is regarded as 48 a highly specialized associative brain region roughly subdivided into a superior, medial and inferior gyrus 49 that is highly interconnected with the limbic and various sensory systems. In addition, it is well documented 50 that the TLN represents a homotypic granular, six-layered associative neocortex comparable in its 51 cytoarchitecture with primary sensory cortices but different to heterotypic agranular motor cortex (von 52 Economo and Koskinas 1925;Vogt 2009;Zilles et al. 2015, Zilles andPalomero-Gallagher 2017).The 53 growing interest in the TLN is motivated by its importance in high-order brain functions as audition, vision, 54 memory, language processing, and various multimodal associations. Moreover, the temporal lobe is also 55 involved in several neurological diseases most importantly as the area of origin and onset of temporal lobe 56 epilepsy (TLE; reviewed by Allone et al. 2017;Tai et al. 2018). TLE is the most common form of refractory 57 epilepsy characterized by recurrent, unprovoked focal seizures that may, with progressing disease, also 58 spread to other areas of the brain. Taken together, the TLN represents an important region in the normal and 59 pathologically altered brain in humans. However, relatively little is known about its neural (but see DeFelipe 60 2011; Mohan et al. 2015) and ...