Chandelier Cartridge Density Is Reduced in the Prefrontal Cortex in Autism

Abstract

An alteration in the balance of excitation-inhibition has been proposed as a common characteristic of the cerebral cortex in autism, which may be due to an alteration in the number and/or function of the excitatory and/or inhibitory cells that form the cortical circuitry. We previously found a decreased number of the parvalbumin (PV)+ interneuron known as Chandelier (Ch) cell in the prefrontal cortex in autism. This decrease could result from a decreased number of Ch cells, but also from decreased PV protein expression by Ch cells. To further determine if Ch cell number is altered in autism, we quantified the number of Ch cells following a different approach and different patient cohort than in our previous studies. We quantified the number of Ch cell cartridges-rather than Ch cell somata-that expressed GAT1-rather than PV. Specifically, we quantified GAT1+ cartridges in prefrontal areas BA9, BA46, and BA47 of 11 cases with autism and 11 control cases. We found that the density of GAT1+ cartridges was decreased in autism in all areas and layers. Whether this alteration is cause or effect remains unclear but could result from alterations that take place during cortical prenatal and/or postnatal development.

Keywords: GAT1; autism; cartridge; chandelier cell; parvalbumin; postmortem.

Figure 1

(A) Prefrontal regions selected for this study: BA9, BA46, and BA47. (B) Nissl-stained columns of the prefrontal regions of interest. Scale bar: 300 μm.

Figure 2

(A) GAT1 immunostaining of BA9 prefrontal cortex in a control case. (B and C) High magnification of cartridges outlines in A, located in upper (B) and lower (C) layers. Scale bar: 500 μm in (A), 25 μm in (B).

Figure 3

Representation of the average cartridge distribution within cortical areas BA9 (A), BA46 (B), and BA47 (C) for control and autism cases. Cases of autism have less cartridges that control cases for the same area. Scale bar: 500 μm.

Figure 4

Number of cartridges in the whole radial dimension (total), supragranular layers, and infragranular layers, in the cerebral cortex in control and autism cases in BA9 (A), BA46 (B), and BA47 (C). There is a significant decrease in the number of cartridges in all cases. Horizontal bar represents the mean and whiskers the standard deviations.

Figure 5

An alteration in the process of generation (1), migration (2), and/or cell death (3) could be responsible for the decreased number of Ch cells that we described in autism.