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Nicotine receptors mediating sensorimotor gating and its enhancement by systemic nicotine

Prepulse inhibition (PPI) of startle occurs when intensity stimuli precede stronger startle-inducing stimuli by 10–1000 ms. PPI deficits are found in individuals with schizophrenia and other psychiatric disorders, and they correlate with other cognitive impairments. Animal research and clinical stud...

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Autores principales: Pinnock, Farena, Bosch, Daniel, Brown, Tyler, Simons, Nadine, Yeomans, John R., DeOliveira, Cleusa, Schmid, Susanne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324144/
https://www.ncbi.nlm.nih.gov/pubmed/25717295
http://dx.doi.org/10.3389/fnbeh.2015.00030
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author Pinnock, Farena
Bosch, Daniel
Brown, Tyler
Simons, Nadine
Yeomans, John R.
DeOliveira, Cleusa
Schmid, Susanne
author_facet Pinnock, Farena
Bosch, Daniel
Brown, Tyler
Simons, Nadine
Yeomans, John R.
DeOliveira, Cleusa
Schmid, Susanne
author_sort Pinnock, Farena
collection PubMed
description Prepulse inhibition (PPI) of startle occurs when intensity stimuli precede stronger startle-inducing stimuli by 10–1000 ms. PPI deficits are found in individuals with schizophrenia and other psychiatric disorders, and they correlate with other cognitive impairments. Animal research and clinical studies have demonstrated that both PPI and cognitive function can be enhanced by nicotine. PPI has been shown to be mediated, at least in part, by mesopontine cholinergic neurons that project to pontine startle neurons and activate muscarinic and potentially nicotine receptors (nAChRs). The subtypes and anatomical location of nAChRs involved in mediating and modulating PPI remain unresolved. We tested the hypothesis that nAChRs that are expressed by pontine startle neurons contribute to PPI. We also explored whether or not these pontine receptors are responsible for the nicotine enhancement of PPI. While systemic administration of nAChR antagonists had limited effects on PPI, PnC microinfusions of the non-α7nAChR preferring antagonist TMPH, but not of the α7nAChR antagonist MLA, into the PnC significantly reduced PPI. Electrophysiological recordings from startle-mediating PnC neurons confirmed that nicotine affects excitability of PnC neurons, which could be antagonized by TMPH, but not by MLA, indicating the expression of non-α7nAChR. In contrast, systemic nicotine enhancement of PPI was only reversed by systemic MLA and not by TMPH or local microinfusions of MLA into the PnC. In summary, our data indicate that non-α7nAChRs in the PnC contribute to PPI at stimulus intervals of 100 ms or less, whereas activation of α7nAChRs in other brain areas is responsible for the systemic nicotine enhancement of PPI. This is important knowledge for the correct interpretation of behavioral, preclinical, and clinical data as well as for developing drugs for the amelioration of PPI deficits and the enhancement of cognitive function.
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spelling pubmed-43241442015-02-25 Nicotine receptors mediating sensorimotor gating and its enhancement by systemic nicotine Pinnock, Farena Bosch, Daniel Brown, Tyler Simons, Nadine Yeomans, John R. DeOliveira, Cleusa Schmid, Susanne Front Behav Neurosci Neuroscience Prepulse inhibition (PPI) of startle occurs when intensity stimuli precede stronger startle-inducing stimuli by 10–1000 ms. PPI deficits are found in individuals with schizophrenia and other psychiatric disorders, and they correlate with other cognitive impairments. Animal research and clinical studies have demonstrated that both PPI and cognitive function can be enhanced by nicotine. PPI has been shown to be mediated, at least in part, by mesopontine cholinergic neurons that project to pontine startle neurons and activate muscarinic and potentially nicotine receptors (nAChRs). The subtypes and anatomical location of nAChRs involved in mediating and modulating PPI remain unresolved. We tested the hypothesis that nAChRs that are expressed by pontine startle neurons contribute to PPI. We also explored whether or not these pontine receptors are responsible for the nicotine enhancement of PPI. While systemic administration of nAChR antagonists had limited effects on PPI, PnC microinfusions of the non-α7nAChR preferring antagonist TMPH, but not of the α7nAChR antagonist MLA, into the PnC significantly reduced PPI. Electrophysiological recordings from startle-mediating PnC neurons confirmed that nicotine affects excitability of PnC neurons, which could be antagonized by TMPH, but not by MLA, indicating the expression of non-α7nAChR. In contrast, systemic nicotine enhancement of PPI was only reversed by systemic MLA and not by TMPH or local microinfusions of MLA into the PnC. In summary, our data indicate that non-α7nAChRs in the PnC contribute to PPI at stimulus intervals of 100 ms or less, whereas activation of α7nAChRs in other brain areas is responsible for the systemic nicotine enhancement of PPI. This is important knowledge for the correct interpretation of behavioral, preclinical, and clinical data as well as for developing drugs for the amelioration of PPI deficits and the enhancement of cognitive function. Frontiers Media S.A. 2015-02-11 /pmc/articles/PMC4324144/ /pubmed/25717295 http://dx.doi.org/10.3389/fnbeh.2015.00030 Text en Copyright © 2015 Pinnock, Bosch, Brown, Simons, Yeomans, DeOliveira and Schmid. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Pinnock, Farena
Bosch, Daniel
Brown, Tyler
Simons, Nadine
Yeomans, John R.
DeOliveira, Cleusa
Schmid, Susanne
Nicotine receptors mediating sensorimotor gating and its enhancement by systemic nicotine
title Nicotine receptors mediating sensorimotor gating and its enhancement by systemic nicotine
title_full Nicotine receptors mediating sensorimotor gating and its enhancement by systemic nicotine
title_fullStr Nicotine receptors mediating sensorimotor gating and its enhancement by systemic nicotine
title_full_unstemmed Nicotine receptors mediating sensorimotor gating and its enhancement by systemic nicotine
title_short Nicotine receptors mediating sensorimotor gating and its enhancement by systemic nicotine
title_sort nicotine receptors mediating sensorimotor gating and its enhancement by systemic nicotine
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324144/
https://www.ncbi.nlm.nih.gov/pubmed/25717295
http://dx.doi.org/10.3389/fnbeh.2015.00030
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