Inhibitory interneurons of the human prefrontal cortex display conserved evolution of the phenotype and related genes

Abstract

Inhibitory interneurons participate in local processing circuits, playing a central role in executive cognitive functions of the prefrontal cortex. Although humans differ from other primates in a number of cognitive domains, it is not currently known whether the interneuron system has changed in the course of primate evolution leading to our species. In this study, we examined the distribution of different interneuron subtypes in the prefrontal cortex of anthropoid primates as revealed by immunohistochemistry against the calcium-binding proteins calbindin, calretinin and parvalbumin. In addition, we tested whether genes involved in the specification, differentiation and migration of interneurons show evidence of positive selection in the evolution of humans. Our findings demonstrate that cellular distributions of interneuron subtypes in human prefrontal cortex are similar to other anthropoid primates and can be explained by general scaling rules. Furthermore, genes underlying interneuron development are highly conserved at the amino acid level in primate evolution. Taken together, these results suggest that the prefrontal cortex in humans retains a similar inhibitory circuitry to that in closely related primates, even though it performs functional operations that are unique to our species. Thus, it is likely that other significant modifications to the connectivity and molecular biology of the prefrontal cortex were overlaid on this conserved interneuron architecture in the course of human evolution.

Distinction of Neurons, Glia and Endothelial Cells in the Cerebral Cortex: An Algorithm Based on Cytological Features

“…Use of this approach to quantify the major cell types in the brain can complement and significantly increase the value of studies that use modern molecular or neurochemical labeling techniques to estimate ratios of specific subtypes of cells within a population. Examples of previous studies that used similar approaches include reports showing that inhibitory neurons represent 20–30% of all neurons in the mammalian neocortex and in the frontal cortex of humans they make up approximately 21% of the neuronal population (Hornung and De Tribolet, 1994; Kalus and Senitz, 1996; Benes et al, 2001; Sherwood et al, 2010). These approaches are especially suited for the quantification and comparison of cell types between different cortical areas and brain nuclei.…”

A Dual Comparative Approach: Integrating Lines of Evidence from Human Evolutionary Neuroanatomy and Neurodevelopmental Disorders

“…Through comparative analyses, we can begin to further understand how the function of specialized cells contributes to interspecific variation in cognitive abilities. Previous research, however, has not found differences in inhibitory interneuron numbers or their distribution in cortical areas, including BA 9, BA 4, BA 32, and BA 44, between humans and anthropoid primates [Sherwood et al, 2010]. The conserved phenotype displayed by inhibitory interneurons in the cortex suggests instead that other genetic and regulatory mechanisms contribute to differences in functional regulation of pyramidal cells by inhibitory interneurons.…”

“…In the primate cerebral cortex, approximately 15-30% of neurons are inhibitory, GABAergic interneurons [DeFelipe, 1997; Sherwood et al, 2010]. Inhibitory interneurons of the cerebral cortex serve an important role in modulating excitatory neuronal function, including control of rhythmic oscillations across assemblages of pyramidal neurons [DeFelipe, 1997] important for the regulation of spike-timing dependent synaptic plasticity.…”

Tyrosine hydroxylase-producing neurons in the human cerebral cortex do not colocalize with calcium-binding proteins or the serotonin 3A receptor

“…In the mouse, a subset of cortical interneurons can be identified by the expression of the ionotropic serotonergic receptor subtype, 5-hydroxytryptamine 3A (5-HT 3A R), and this subgroup overlaps with the previously-identified CR subset (Lee et al, 2010; Rudy et al, 2011; Vucurovic et al, 2010). Interneurons in the primate neocortex, likewise, have been subdivided into three neurochemically-distinct groups that contain PV, CR, or another calcium-binding protein calbindin (CB) (Carder et al, 1996; Conde et al, 1994; DeFelipe, 1997; Gabbott et al, 1997; Glezer et al, 1993; Sherwood et al, 2007, 2010; Zaitsev et al, 2009). The presence of 5-HT 3A R in human interneurons has not been reported.…”