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Morphological correlates of sex differences in acoustic startle response and prepulse inhibition through projections from locus coeruleus to cochlear root neurons

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Abstract

The noradrenergic locus coeruleus (LC) plays an important role in the promotion and maintenance of arousal and alertness. Our group recently described coerulean projections to cochlear root neurons (CRNs), the first relay of the primary acoustic startle reflex (ASR) circuit. However, the role of the LC in the ASR and its modulation, prepulse inhibition (PPI), is not clear. In this study, we damaged LC neurons and fibers using a highly selective neurotoxin, DSP-4, and then assessed ASR and PPI in male and female rats. Our results showed that ASR amplitude was higher in males at 14 days after DSP-4 injection when compared to pre-administration values and those in the male control group. Such modifications in ASR amplitude did not occur in DSP-4-injected females, which exhibited ASR amplitude within the range of control values. PPI differences between males and females seen in controls were not observed in DSP-4-injected rats for any interstimulus interval tested. DSP-4 injection did not affect ASR and PPI latencies in either the male or the female groups, showing values that were consistent with the sex-related variability observed in control rats. Furthermore, we studied the noradrenergic receptor system in the cochlear nerve root using gene expression analysis. When compared to controls, DSP-4-injected males showed higher levels of expression in all adrenoceptor subtypes; however, DSP-4-injected females showed varied effects depending on the receptor type, with either up-, downregulations, or maintenance of expression levels. Lastly, we determined noradrenaline levels in CRNs and other LC-targeted areas using HPLC assays, and these results correlated with behavioral and adrenoceptor expression changes post DSP-4 injection. Our study supports the participation of LC in ASR and PPI, and contributes toward a better understanding of sex-related differences observed in somatosensory gating paradigms.

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Abbreviations

ABC:

Avidin–biotin–peroxidase complex

ADRs:

Adrenergic receptors

ASR:

Acoustic startle reflex

BS:

Brainstem

Cb:

Cerebellum

CRNs:

Cochlear root neurons

DAB:

3,3′ Diaminobenzidine tetrahydrochloride

DBH:

Dopamine beta-hydroxylase

DHBA:

3,4-Dihydroxybenzylamine

DSP-4:

N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine

HPAA:

4-Hydroxyphenylacetic acid

HPLC:

High-performance liquid chromatography

IC:

Inferior colliculus

IHC:

Immunohistochemistry

ISI:

Interstimulus interval

LC:

Locus coeruleus

MHPG:

3-Methoxy-4-hydroxyphenylglycol

NA:

Noradrenaline

PFC:

Prefrontal cortex

PB:

Phosphate buffer 0.1 M, pH 7.4

PBS:

Phosphate buffered saline

PPI:

Prepulse inhibition

RT-qPCR:

Reverse transcription-quantitative polymerase chain reaction

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Acknowledgements

The authors declare no conflicts of interest, financial or otherwise. The study was supported in part by the Spanish Grants BFU2010-17754 (MICINN) and SAF2016-78898-C2-2R (MINECO), and by the São Paulo State Research Foundation FAPESP proc. 2008/02771-6. The authors also thank Sonia Hernández for technical support in the experiments; and Brian Swoyer and Kristiina Hormigo for language editing services.

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Authors and Affiliations

  1. Institute for Neuroscience of Castilla y León (INCYL), University of Salamanca, Salamanca, Spain

    Sebastian Hormigo, Ricardo Gómez-Nieto, Consuelo Sancho, Javier Herrero-Turrión, Juan Carro & Dolores E. López

  2. Institute of Biomedical Research of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain

    Ricardo Gómez-Nieto, Consuelo Sancho, Javier Herrero-Turrión & Dolores E. López

  3. Department of Cell Biology and Pathology, University of Salamanca, Salamanca, Spain

    Ricardo Gómez-Nieto & Dolores E. López

  4. Department of Physiology and Pharmacology, University of Salamanca, Salamanca, Spain

    Consuelo Sancho

  5. Department of Anatomy, Institute of Biosciences of Botucatu, Univ. Estadual Paulista (UNESP), Distrito de Rubião Jr., S/N, PO.Box 510, Botucatu, SP, 18618-689, Brazil

    José de Anchieta de Castro e Horta-Júnior

Authors
  1. Sebastian Hormigo
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  2. Ricardo Gómez-Nieto
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  3. Consuelo Sancho
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  4. Javier Herrero-Turrión
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  5. Juan Carro
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  6. Dolores E. López
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  7. José de Anchieta de Castro e Horta-Júnior
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Corresponding authors

Correspondence to Sebastian Hormigo or José de Anchieta de Castro e Horta-Júnior.

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Conflict of interest

This study was supported in part by the Spanish Grants BFU2010-17754 (MICINN) and SAF2016-78898-C2-2R (MINECO) to DEL, and by the São Paulo State Research Foundation FAPESP proc. 2008/02771-6 to JACHJ. The funders did not take part of this study whatsoever, and the authors declare no conflicts of interest, financial or otherwise.

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Hormigo, S., Gómez-Nieto, R., Sancho, C. et al. Morphological correlates of sex differences in acoustic startle response and prepulse inhibition through projections from locus coeruleus to cochlear root neurons. Brain Struct Funct 222, 3491–3508 (2017). https://doi.org/10.1007/s00429-017-1415-1

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  • DOI: https://doi.org/10.1007/s00429-017-1415-1

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