Parvalbumin Stained Cells Are Reduced in the Cerebral Cortex of Individuals with Autism Spectrum Disorders

Background:  Postmortem studies in autism spectrum disorders (ASD) indicate alterations in the number and/or distribution of neurons within the cerebral cortex. The presence of heterotopias and dysplasias create a suitable scenario for an excitatory/inhibitory imbalance capable of explaining some of the core features of the condition.

Objectives:   Here we examine the number and location of interneuronal subpopulations within the prefrontal cortex in autism.  We propose that an alteration in the number and/or type of interneurons could help explain alterations in cognition, sensory problems, and seizures commonly observed in ASD. 

Methods:  To test this hypothesis we collected cortical tissue from 10 male subjects with autism and 10 age (7 to 56 years old) and gender matched neurotypicals. Formalin fixed blocks (2 cm³) containing each area (BA 46, 47 and 9) were collected based on anatomical landmarks. We sectioned blocks into 14 µm sections and performed Nissl staining in three of the sections. We took pictures of each Nissl section and determine the boundaries of each the areas of interest based on the cytoarchitecture of the cortical layers.  The localization in the Nissl stained tissue allowed us to select the region of tissue where immunochemistry was performed. We performed triple immunostaining for markers of the three main cortical interneuron subpopulations: parvalbumin+ (PV); calbindin+ (CB); and calretinin+ (CR). We quantified the number of interneurons that express each marker within each cortical layer, and statistically compared results between groups.

Results:   We found that the number of PV+ interneurons is decreased in upper layers of areas B46 and 47 in autism. Based on the morphology, size and layer distribution of PV+ cells in each group, we propose that the PV+ cells we found to be decreased in upper layers in the prefrontal cortex in autism are most likely Chandellier cells. 

Conclusions:   Chandellier cells are crucial for proper cortical function. Chandellier cells are the only cortical interneurons that synapse on the initial axon segment of pyramidal neurons, thereby controlling the output signal from pyramidal cells. The variability in the number of lost PV+ cells in the cortex with autism might explain the presence of seizures in some patients with autism. Using the same tissue, we are currently investigating PV+ chandelier cell terminals within each cortical layer. Exploring whether and how Chandellier interneurons are altered in autism will open new lines of research that focus on the modulation of signaling factors and genes that control interneuronal genesis, migration, and survival, as well as on transmission of electrical signals between cortical neurons in autism.