Research from the Abdus-Saboor Lab Published in Cell

Brittany Bistis
January 25, 2023

How does physical touch elicit an emotional reaction? Our bodies differentiate between human-human physical contact that is pleasurable, painful, or just awkward. A large body of literature focuses on the role of the brain in the emotional side of physical touch processing. The Abdus-Saboor lab recently published a study in Cell that demonstrates an important, specific role for sensory neurons in the skin in communicating rewarding physical touch to the brain.

To investigate rewarding touch circuits in the peripheral nervous system, the Abdus-Saboor lab studies pleasure-associated behaviors in mice. When stroked on the back by a soft swab of cotton or by a male mouse she deems acceptable, a female mouse will stretch out her neck and dip her back. Former students in the lab of Dr. Ishmail Abdus-Saboor, Dr. Leah Elias and Will Foster found they could get their transgenic female mice to do this behavior just by shining a blue light on them. The mice reacted as if they had been physically touched. “We knew we stumbled on something big,” said Dr. Abdus-Saboor, “When I saw the data I immediately began running through the halls telling any colleague who would listen. Even with just our first animal, I knew we had discovered something important.”

These transgenic mice were engineered to express a light-sensitive protein in a small population of sensory neurons. These sensory neurons specifically innervated the hairy skin and are typified by expression of the cell membrane receptor protein MRGPRB4. With this scheme, the Abdus-Saboor lab is able to stimulate MRGPRB4+ neurons simply by stimulating the blue-light activated channel. When Dr. Elias shone blue light on her mice, she was able to capture how their positive “back-dipping” response with high-speed videography.

The Abdus-Saboor lab then sought to quantify how pleasurable the activation of the MRGPRB4+ sensory neurons is. Dr. Elias placed a mouse in a multi-chamber pen and shone light on it when it was in one specific chamber. She found that the mice began to prefer to spend time in the chamber where they had received the MRGPRB4+ neuron-activating light. This further indicated that activation of these neurons is rewarding. Selectively killing these B4+ neurons with a toxin engineered to only be active in this cell population, resulted in female mice that did not seem to enjoy gentle stroking and were unreceptive to the physical overtures of a male mouse, while activating these B4+ neurons triggered a dopamine release in the female mouse brain.

“This study highlights the untapped potential of targeting the peripheral nervous system to alter behavior and reward circuits in the brain,” said Dr. Abdus-Saboor, “Moreover, pathways such as the one we identified might be altered in disease states like autism, where social touch often loses its rewarding quality.”