The Number of Parvalbumin-Expressing Chandellier and Basket Cells Are Differentially Decreased in Medial Prefrontal Cortex in Autism

Background:  

Cortical interneurons have been linked with the altered balance of excitation / inhibition in the cerebral cortex that is present in autism. However, a specific subtype of interneuron had not been correlated with autism until we discovered that the number of parvalbumin (PV) expressing interneurons was decreased in the prefrontal cortex in autism. PV+ interneurons are the primary cortical interneuron that directly innervates the pyramidal neuron soma or axon initial segment. There are two PV+ interneuron subtypes: Basket (Bsk) cells and Chandellier (Ch) cells. Bsk cells innervate the soma and proximal dendrites of pyramidal neurons, while Ch cells innervate the initial segment of pyramidal neuron axon. Both Bsk and Ch cells are fast-spiking neurons that innervate a large number of pyramidal neurons, and therefore even a small decrease in Ch or Bsk cell number could critically impair pyramidal neuron output and regional cortical function.  These cells account for only 1% of total neurons in the cerebral cortex, with Bsk cells more numerous than Ch cells. 

Objectives:  

We investigated whether one subtype of the PV+ cells, the Bsk or Ch cell, or both, was decreased in the medial prefrontal cortex (Brodmann areas (BA) 46, 47, and 9) in autism. 

Methods:  

A specific marker that differentiates Bsk from Ch cells has not been devised. However, we have designed a method that allows us to discern between these two cell types. Our method is based on the differential expression of Vicia villosa lectin (VVA) by Bsk and Ch cells. VVA lectin belongs to a family of tetrameric glycoproteins that binds to N-acetylgalactosamine, which is present in the perineuronal net surrounding Bsk cells. While the vast majority of Bsk cells can be labeled using VVA, Ch cells do not express VVA. We used PV and VVA double labeling, and based on exclusion distinguished Ch cells from Bsk cells in cortical slices of prefrontal cortex in autism and control groups. We then quantified the number of each cell type (PV+/VVA+; PV+AVV-) present in each Brodmann area in our tissue samples and compared data between autism and control groups. 

Results:  

We found that PV+ Ch cells (VVA-) but not PV+ Bsk cells (VVA+) are decreased in prefrontal BA46 and BA47, while both PV+ Chk and PV+ Bs cells are decreased in prefrontal BA9.

Conclusions:

The changes in PV+ Ch and PV+ Bsk cells reported here may reflect altered information processing within the PFC and could contribute to the cognitive impairments seen in autism.