Regional specialization of upper-layer inhibitory interneuron organization in the human prefrontal cortex

Area of Science:

• Neuroscience
• Neuroanatomy
• Cellular Neuroscience

Background:

• GABAergic interneurons are crucial for cortical microcircuit function.
• The anatomical organization of interneuron populations in the human prefrontal cortex is not well understood.
• Understanding these populations is key to deciphering prefrontal cortex function.

Purpose of the Study:

• To investigate the laminar distribution and regional organization of major GABAergic interneuron populations.
• To compare these populations in the dorsal (Brodmann area 9) and ventral (Brodmann area 14r) human prefrontal cortex.
• To identify region-specific specializations in inhibitory interneuron organization.

Main Methods:

• Analysis of postmortem human prefrontal cortex tissue from five adult male brains.
• Use of molecular markers: calretinin (CR), parvalbumin (PV), calbindin (CB), and somatostatin (SOM).
• Double-labeling immunofluorescence and RNAscope in situ hybridization to confirm phenotypes and overlaps.

Main Results:

• Calretinin+ (CR+) neurons were the largest interneuron population, enriched in supragranular layers.
• Parvalbumin+ (PV+) neurons concentrated in layers III-IV; Somatostatin+ (SOM+) neurons were more uniformly distributed.
• Ventral prefrontal cortex (BA14r) had a significantly higher proportion of CR+ neurons than dorsal (BA9), indicating region-specific differences.

Conclusions:

• Significant regional specialization exists in the organization of inhibitory interneurons within the human prefrontal cortex.
• Differences in supragranular inhibitory circuitry may underlie distinct functional architectures of dorsal and ventral prefrontal networks.
• These findings provide critical anatomical insights into prefrontal cortex functional specialization.