Abstract
Many neuropsychiatric disorders, such as schizophrenia, have been associated with olfactory dysfunction and abnormalities in the prepulse inhibition (PPI) response to a startle reflex. However, whether these two abnormalities could be related is unclear. The present investigations were designed to determine whether theblockage of olfactory sensory input by zinc sulfate infusion in the olfactory naris (0.5 ml, 0.17 M, ZnE) can disturb the PPI response. Furthermore, a bilateral microinjection of lidocaine/MK801 in the olfactory bulb (OB) was administered to examine whether the blockage of olfactory sensory input could impair the PPI response. To identify the neural projection between olfaction and PPI-related areas, trans-synaptic retrograde tracing with the recombinant pseudorabies virus (PRV) was used. Our results demonstrated that blockage of olfactory sensory input could disturb olfactory behavior. In the function studies, we demonstrated that blockage of olfactory sensory input could impair the pre-pulse inhibition of the startle response following decreased c-Fos expression in relevant brain regions during the PPI responses. Furthermore, similar and more robust findings indicated that blockage of olfactory sensory input by microinjection of lidocaine/MK801 in the OB could impair the PPI response. In the circuit-level studies, we demonstrated that trans-synaptic retrograde tracing with PRV exhibited a large portion of labeled neurons in several regions of the olfactory cortices from the pedunculopontine tegmental nucleus (PPTg). Thus, these data suggest that the olfactory system participates in the PPI regulating fields and plays a role in the pre-pulse inhibition of the startle response in rats.
Highlights
An intact nervous system engages a variety of mechanisms to suppress or ‘‘filter out’’ irrelevant information in sensory, cognitive and motor domains to enable an individual to focus on the most salient stimuli in the environment (Braff and Geyer, 1990)
All animals were treated in accordance with the Wuhan Institute of Physics and Mathematics (WIPM), Chinese Academy of Sciences (CAS) guidelines regarding the practice of animal care
When the lemon odor was replaced by a novel odor in the discrimination test, pairwise comparisons indicated that the control animals spent more time investigating the mint odor than the mineral oil (p < 0.05), whereas the animals that received the ZnE application to the naris did not exhibit a significant difference in their sniffing times between the mint and control odors (Figures 1A,B)
Summary
An intact nervous system engages a variety of mechanisms to suppress or ‘‘filter out’’ irrelevant information in sensory, cognitive and motor domains to enable an individual to focus on the most salient stimuli in the environment (Braff and Geyer, 1990). Olfaction was included in PPI studies have demonstrated that many neuropsychiatric disorders exhibit an impaired ability to suppress irrelevant information. Patients with schizophrenia exhibited impairments in automatically filtering irrelevant thoughts and sensory stimuli (Geyer et al, 2002). Clinical observations have demonstrated that olfactory dysfunction occurred in neuropsychiatric disorders (Martzke et al, 1997). In rodents, some animal models of neuropsychiatric disease have been demonstrated to exhibit olfactory dysfunction (Huckins et al, 2013). Whether there is a relationship between olfactory dysfunction and an abnormal PPI is unclear
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