Histamine and acetylcholine receptor involvement in sensorimotor gating: an autoradiography study

Sensory gating is a way by which the brain manages sensory information flow. For optimal allocation of neural resources, it is important to be able to screen out (or “gate”) irrelevant sensory information when another stimulus is being processed.  Sensorimotor gating more generally refers to the overall process of modulation of the motor responses to sensory stimuli.  Impaired sensorimotor gating is seen in a variety of neurobehavioral disorders including schizophrenia, autism and sensory processing disorder. The degree of sensorimotor gating can be studied behaviorally by indexing prepulse inhibition (PPI). PPI reflects the degree of suppression of a startle response to an intense sensory stimulus when it is preceded by a more modest sensory stimulus. The neural circuitry underlying PPI has been shown to include dopaminergic and cholinergic systems. We previously found that histaminergic H1 receptors also play important roles in sensorimotor gating: the acute administration of the histamine H1 antagonist, pyrilamine, significantly reverses the PPI impairment caused by the NMDA glutamate antagonist, dizocilpine (MK-801). The current study was conducted to determine the anatomic bases for histaminergic and cholinergic regulation of the effect of NMDA antagonism on PPI.  Using autoradiography, we found that pyrilamine treatment decreased H1 receptor binding in the anterior cingulate, which correlated with PPI improvement.  Furthermore, we found that pyrilamine treatment resulted in increased α7-nicotinic acetylcholine receptor binding in the insular cortex, which also correlated with PPI improvement.  These findings shed light on the interaction between histamine and acetylcholine signaling in a distributed network of PPI modulation.