Morphological analysis of human and mouse dendritic spines reveals a morphological continuum and differences across ages and species

Abstract

Dendritic spines have diverse morphologies, with a wide range of head and neck sizes, and these morphological differences likely generate different functional properties. To explore how this morphological diversity differs across species and ages we analyzed 3D confocal reconstructions of ∼8,000 human spines and ∼1,700 mouse spines, labeled by intracellular injections in fixed tissue. Using unsupervised algorithms, we computationally separated spine heads and necks and systematically measured morphological features of spines in apical and basal dendrites from cortical pyramidal cells. Human spines had unimodal distributions of parameters, without any evidence of morphological subtypes. Their spine necks were longer and thinner in apical than in basal spines, and spine head volumes of an 85-years-old individual were larger than those of a 40-years-old individual. Human spines had longer and thicker necks and larger head volumes than mouse spines. Our results indicate that human spines form part of a morphological continuum, are larger and longer than those of mice, and become larger with increasing adult age. These morphological differences in spines across species could generate functional differences in biochemical and electrical spine compartmentalization, or in synaptic properties, across species and ages.

Significance Statement

Dendritic spines mediate most excitatory contacts in the brain and enable biochemical and electrical compartmentalization. Spine morphologies are diverse and this diversity likely has functional consequences. Here, we use unsupervised algorithms to computationally dissect spine heads and necks and systematically measure morphological features of spines from light microscopy datasets of mouse and human cortex. Human spines form part of a morphological continuum, without evidence of subtypes. Human spines also have longer and thicker necks and bigger head volumes than mouse spines. Our results demonstrate a rich morphological diversity of human spines, and systematic differences across ages and species.