Dysgranular retrosplenial cortex modulates histaminergic and nonhistaminergic itch processing

Area of Science:

• Neuroscience
• Behavioral Science

Background:

• Itch is a complex sensation often leading to scratching.
• The anterior cingulate cortex and prelimbic cortex are known to modulate itch.
• The role of the retrosplenial cortex (RSC) in itch processing remains largely unexplored.

Purpose of the Study:

• To investigate the involvement of the dysgranular retrosplenial cortex (RSCd) in itch modulation.
• To identify specific neuronal populations and pathways within the RSCd that regulate itch-scratching behavior.

Main Methods:

• Utilized c-Fos immunohistochemistry and fiber photometry to measure neuronal activity in the RSCd during itch.
• Employed designer receptors exclusively activated by designer drugs (DREADDs) for pharmacogenetic manipulation of RSCd neurons.
• Investigated the effects of inhibiting global RSCd neurons, pyramidal neurons within RSCd, and projections from the caudal anterior cingulate cortex (cACC) to RSCd.
• Assessed scratching behavior in response to 5-HT or compound 48/80 injections in rats.
• Evaluated motor ability to rule out non-specific effects.

Main Results:

• Neuronal activity in the RSCd was significantly elevated during itch-scratching processing.
• Pharmacogenetic inhibition of RSCd neurons reduced the frequency and duration of scratching.
• Selective inhibition of RSCd pyramidal neurons or cACC to RSCd excitatory projections also decreased itch-related scratching.
• Motor function remained unaffected by the interventions.

Conclusions:

• The dysgranular retrosplenial cortex (RSCd), particularly its pyramidal neurons, is critically involved in the central regulation of itch.
• Excitatory projections from the caudal anterior cingulate cortex (cACC) to the RSCd are important for itch processing.
• These findings highlight a novel neural circuit for controlling both histaminergic and non-histaminergic itch.