Dendritic spines function as the primary site for excitatory synaptic contacts on cortical pyramidal cells. Previous research on dendritic spines in autism spectrum disorders (ASD) has shown an increased density of spines on cortical pyramidal cells (Hutsler & Zhang, 2010). Morphological features of spines such as length, width, and the size of the head all have functional significance in neuronal signaling and can be related to spine maturity (Yuste & Majewska, 2000). Given this structure-function relationship, alongside the fact that dendritic spines in Fragile X Syndrome show morphological and density differences compared to neurotypicals, we aim to assess potential alterations to the morphology of dendritic spines in ASD.
Objectives:
The aim of the present study was to assess dendritic spine morphology on cortical pyramidal cells in ASD versus neurotypical subjects. Because spine morphology is relatable to functional significance, alterations in ASD may provide useful information about disrupted inter-neuronal signaling.
Methods:
Post-mortem tissue was acquired from 8 male subjects (4 ASD, 4 neurotypicals). Tissue blocks were taken from the superior temporal gyrus (BA 21), dorsolateral frontal lobes (BA 9), and dorsal parietal lobes (BA 7). The tissue samples were sectioned perpendicular to the gyral axis then stained using a modified Golgi-Kopsch method. Pyramidal cells from cortical layers 2, 3, and 5 were selected at 100x magnification and individual spines were manually analyzed at 1000x magnification on measures of length, thickness, and presence of a head. Data were collected from 5 cells per layer in all 3 regions examined, resulting in approximately 45 cells per case and over 20,000 spines. Synaptic spines were analyzed based on length, distance from the cell body, as well as categorical data (thin versus not thin, head versus no head).
Results:
On average, ASD subjects had longer spines than control subjects. In addition, ASD subjects showed comparable spine lengths in layers 2, 3, and 5 within each region examined, while control subjects’ spine length decreased across layers 2, 3, and 5. Finally, ASD subjects showed a significantly lower proportion of spines with heads relative to neurotypical subjects (Odds Ratio = 1.945, p < .001).
Conclusions:
These results show that ASD subjects exhibit longer spine lengths compared to neurotypicals. This may indicate a greater proportion of immature spines in the autistic brain. Additionally, the fact that ASD subjects show a lower proportion of spines with a head relative to neurotypical subjects indicates a weakened number of synaptic contacts (Yuste & Majewska, 2000) among dendritic spines on cortical pyramidal cells in the autistic brain. These results provide the first systematic demonstration of cortical spine dysmorphology in autism spectrum disorders.