Central Medial Thalamic Nucleus Dynamically Participates in Acute Itch Sensation and Chronic Itch-Induced Anxiety-Like Behavior in Male Mice

Itch is an annoying sensation consisting of both sensory and emotional components. It is known to involve the parabrachial nucleus (PBN), but the following transmission nodes remain elusive. The present study identified that the PBN-central medial thalamic nucleus (CM)-medial prefrontal cortex (mPFC) pathway is essential for itch signal transmission at the supraspinal level in male mice. Chemogenetic inhibition of the CM-mPFC pathway attenuates scratching behavior or chronic itch-related affective responses. CM input to mPFC pyramidal neurons is enhanced in acute and chronic itch models. Specifically chronic itch stimuli also alter mPFC interneuron involvement, resulting in enhanced feedforward inhibition and a distorted excitatory/inhibitory balance in mPFC pyramidal neurons. The present work underscores CM as a transmit node of the itch signal in the thalamus, which is dynamically engaged in both the sensory and affective dimensions of itch with different stimulus salience. Itch is known to involve the parabrachial nucleus, but the following transmission nodes remain elusive. Here, the authors show in male mice that the central medial thalamic nucleus—medial prefrontal cortex (mPFC) pathway transmits itch signals and is involved in both acute scratching and chronic itch-related affective behavior, with an altered excitatory/inhibitory balance in mPFC in chronic itch models.