Fig. 4
Neuronal populations in LPFC layer 1 change in parallel between children and adults with and without autism. a There was a trend towards a reduction in neuron density between neurotypical children and adults. Neuron density values were normalized such that the highest density has a value of 1. Cases used in this analysis: 451, 4337, M3835 M, 6004, 4981, HAW, HAY, HCD, HCF. b There was a reduction in neuron density between typical children and adults, with a ratio of mean neuron density in children/adults of approximately 1.27. c Mean neuron density in adults with and without autism (mean control = 6602 ± 1186 cells/mm3, mean autism = 6939 ± 217 neurons/mm3) was not statistically different. d The decrease in neuron density from childhood to adulthood was not different between groups. e There was a trend towards an increase in neuron density with age between young and older adults. f The area fraction containing cells increased slightly in neurotypical development, likely representing simultaneous dilution of neurons within the neuropil and expansion of glial cell populations with age. g There was no difference between the percent surface area occupied by cells between autistic and neurotypical groups. h CR neuron density increased between children and adults. In this sample, this trend was primarily driven by high density of CR neurons in older adults. The solid line shows the overall trend towards an increase in CR neuron density with age, the dotted line shows the decrease in CR neuron density when comparing children and young adults i The trend towards a decrease in CR neuron density in layer 1 was similar in neurotypical individuals and individuals with autism. j PV neurons were present in layer 1 in neurotypical children; their density decreased significantly in adults, and in many adult cases these neurons were not found. k PV neurons were prominent in layer 1 of non-autistic (mean = 329 ± 69 neurons/mm3) and autistic children (mean = 312 ± 231 neurons/mm3), and their density decreased significantly in adults (mean control = 33 ± 39 cells/mm3, mean autism =15 ± 26 neurons/mm3, p = 0.006). l We calculated the relative proportions of the three inhibitory interneuron subtypes in layer 1. CR was the most prominent inhibitory interneuron subtype, labeling 73.07 ± 16.07% of labeled neurons. CB was expressed by 16.32 ± 15.81% of labeled inhibitory neurons, while PV was the least prominent interneuron subtype labeling only 10.60 ± 9.10% of labeled interneurons in layer 1. m 88.44 ± 7.24% of neurons were not labeled with calcium binding proteins in layer 1. n We calculated mean inhibitory neuron densities, including cases of all ages. CR-immunoreactive neurons were the densest neuron population (mean control = 1385 ± 696 neurons/mm3, mean autism = 1436 ± 733 neurons/mm3), followed by CB- (mean control = 194 ± 127 neurons/mm3, mean autism = 138 ± 124 neurons/mm3) and PV- neurons (mean control = 220 ± 215 neurons/mm3, mean autism = 248 ± 239 neurons/mm3). There were no significant differences between groups. Autism cases AN 03345, 1182, AN 04682, and B-6677 and control case HCF were not included in CR quantitative analyses due to inconsistent staining. Autism case B-6677 was not included in PV quantitative analyses due to inconsistent staining. Left panels in g-k present developmental trends on a case-by-case basis, and right panels show mean ± SD for children and adults