Innovations present in the primate interneuron repertoire.

Area of Science:

• Neuroscience
• Evolutionary Biology
• Genomics

Background:

• Primates and rodents share a common ancestor but exhibit significant behavioral and cognitive differences.
• The cellular basis for these interspecies brain variations remains largely unknown.

Purpose of the Study:

• To investigate the cellular and molecular underpinnings of brain differences between primates and rodents.
• To identify homologous interneuron types and their expression patterns across species.

Main Methods:

• Single-nucleus RNA sequencing was employed to profile RNA expression in individual interneurons.
• Comparative analysis was performed on homologous brain regions from humans, macaques, marmosets, mice, and ferrets.

Main Results:

• Homologous interneuron types were identified but varied in abundance and gene expression across species, with less variation among primates.
• A significant fraction of species-specific interneuron marker genes lacked conservation across species.
• The 'ivy cell' interneuron type, found in the mouse hippocampus, is abundant in the primate neocortex but absent in mice and ferrets.
• A novel primate-specific striatal interneuron type, constituting approximately 30% of striatal interneurons, was discovered.

Conclusions:

• Evolutionary divergence has led to distinct interneuron populations and gene expression profiles in primate and rodent brains.
• Regional cortical context influences RNA expression patterns in adult neocortical interneurons.
• The emergence of novel interneuron types in primates, particularly in the striatum, highlights unique evolutionary adaptations.