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

Jerry Skefos,Melissa Ghulam,Jose Larrauri,Edward Levin,Margaret Bauman,Arjun Mahendra,Gaurang Patel,Ehsan Kholdebarin

doi:10.12688/f1000research.4287.1

Jerry Skefos, Melissa Ghulam + Show 6 more

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https://doi.org/10.12688/f1000research.4287.1

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Abstract

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.

Highlights

Sudden intense sensory stimuli can evoke a rapid muscular reaction called the startle response
In the present study we show that chronic pyrilamine administration prevents the prepulse inhibition (PPI) impairment induced by chronic dizocilpine administration, an effect that is correlated with a reduction in ligand-binding potential of H1 receptors in the anterior cingulate and an increase in nicotinic receptor α7 subunit binding in the insular cortex
Pyrilamine treatment reverses PPI impairment in dizocilpinetreated rats prepulse intensity did not significantly affect inhibition of the startle response, we did observe a trend towards increased PPI with increased prepulse intensity (Figure 2, Dataset 1)

Summary

Introduction

Sudden intense sensory stimuli can evoke a rapid muscular reaction called the startle response. PPI is believed to entail sensory gating mechanisms as well as direct motor reflex inhibition. An expansive network of brain regions underlies startle, PPI, and modulation of PPI. This network includes nuclei within the pontine reticular system, the superior and inferior colliculi, substantia nigra, basolateral amygdala, hippocampus, thalamus, prefrontal cortex, ventral pallidum, striatum, and ventral tegmental area (Swerdlow et al, 2001). PPI is believed to be related to an individual’s ability to filter incoming sensory information as well as inhibit resultant behavior (Braff et al, 2001; Rabin et al, 2009), and has been shown to be impaired in a number of neuropsychological disorders including schizophrenia and autism (Braff et al, 2001). PPI is a useful experimental technique used to investigate sensorimotor gating mechanisms and test therapeutic treatments in animal models of neurologic disease as well as in clinical populations, most extensively in patients with schizophrenia (Swerdlow et al, 2008)

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