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Direct and indirect nigrofugal projections to the nucleus reticularis pontis caudalis mediate in the motor execution of the acoustic startle reflex

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Abstract

The acoustic startle reflex (ASR) is a short and intense defensive reaction in response to a loud and unexpected acoustic stimulus. In the rat, a primary startle pathway encompasses three serially connected central structures: the cochlear root neurons, the giant neurons of the nucleus reticularis pontis caudalis (PnC), and the spinal motoneurons. As a sensorimotor interface, the PnC has a central role in the ASR circuitry, especially the integration of different sensory stimuli and brain states into initiation of motor responses. Since the basal ganglia circuits control movement and action selection, we hypothesize that their output via the substantia nigra (SN) may interplay with the ASR primary circuit by providing inputs to PnC. Moreover, the pedunculopontine tegmental nucleus (PPTg) has been proposed as a functional and neural extension of the SN, so it is another goal of this study to describe possible anatomical connections from the PPTg to PnC. Here, we made 6-OHDA neurotoxic lesions of the SN pars compacta (SNc) and submitted the rats to a custom-built ASR measurement session to assess amplitude and latency of motor responses. We found that following lesion of the SNc, ASR amplitude decreased and latency increased compared to those values from the sham-surgery and control groups. The number of dopamine neurons remaining in the SNc after lesion was also estimated using a stereological approach, and it correlated with our behavioral results. Moreover, we employed neural tract-tracing techniques to highlight direct projections from the SN to PnC, and indirect projections through the PPTg. Finally, we also measured levels of excitatory amino acid neurotransmitters in the PnC following lesion of the SN, and found that they change following an ipsi/contralateral pattern. Taken together, our results identify nigrofugal efferents onto the primary ASR circuit that may modulate motor responses.

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Abbreviations

6-OHDA:

6-Hydroxydopamine

ABC:

Avidin-biotin-peroxidase complex

Arg:

Arginine

Asp:

Aspartate

ASR:

Acoustic startle reflex

BDA:

Biotinylated dextran amine

Cb:

Cerebellum

CE-LIFD:

Capillary electrophoresis laser-induced fluorescence detection

CRNs:

Cochlear root neurons

CP:

Cerebellar peduncle

FG:

FluoroGold

GABA:

γ-Aminobutyric acid

Glu:

Glutamate

GP:

Globus pallidus

IC:

Inferior colliculus

IHC:

Immunohistochemistry

i.m.:

Intramuscular

i.p.:

Intraperitoneal

IV:

Trochlear nucleus

LL:

Lateral lemniscus

m.w.:

Molecular weight

PAG:

Periaqueductal grey

PB:

Phosphate buffer

PnC:

Nucleus reticularis pontis caudalis

PnO:

Oral pontine reticular nucleus

PPTg:

Pedunculopontine tegmental nucleus

SC:

Superior colliculus

SN:

Substantia nigra

SNc:

Substantia nigra pars compacta

SNr:

Substantia nigra pars reticulata

SOC:

Superior olivary complex

TH-ir:

Tyrosine-hydroxylase immunoreactivity

VII:

Facial nerve

VIII:

Auditory-vestibular nerve

VTA:

Ventral tegmental area

xcp:

Cerebellar peduncle, decussation

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Acknowledgements

The authors declare no conflicts of interest, financial or otherwise. This study was supported in part by Spanish grants SAF2016-78898-C2-2R (MINECO) and by the University of Salamanca Research Support Grant for GIRs 2017. We would like to thank T. López-Albuquerque for his input in the design of this study, 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, C/ Pintor Fernando Gallego, 1, 37007, Salamanca, Spain

    Sebastian Hormigo, Dolores E. López, Antonio Cardoso & Orlando Castellano

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

    Dolores E. López & Orlando Castellano

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

    Dolores E. López & Orlando Castellano

  4. Department of Nursing and Physical Therapy, University of Salamanca, Salamanca, Spain

    Antonio Cardoso

  5. Department of Pharmacology, Faculty of Biological Sciences, University of Concepción, Concepción, Chile

    Gladys Zapata & Jacqueline Sepúlveda

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  1. Sebastian Hormigo
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  2. Dolores E. López
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  5. Jacqueline Sepúlveda
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  6. Orlando Castellano
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Correspondence to Orlando Castellano.

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Conflict of interest

This study was supported in part by Spanish grants SAF2016-78898-C2-2R (MINECO) and by the University of Salamanca Research Support Grant for GIRs 2017. The funders did not take part in this study whatsoever, and the authors declare no competing conflicts of interest, financial, or otherwise.

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429_2018_1654_MOESM1_ESM.tif

Supplementary Figure 1. Distribution of TH staining in PPTg and PnC after 6-OHDA unilateral lesions of the SNc. A, TH-labeled fibers in the PPTg region in a sham-surgery control case. A1, inset microphotograph of the white square frame in (A) B, TH-labeled fibers in the PnC region in a sham-surgery control case. B1, inset microphotograph of the white square frame in (B) C, TH-labeled fibers in the PPTg region in a representative 6-OHDA neurotoxic lesion of SNc case. C1, inset microphotograph of the white square frame in (C) D, TH-labeled fibers in the PnC region in a representative 6-OHDA neurotoxic lesion of SNc case. D1, inset microphotograph of the white square frame in (D) Note a decrease in the TH-labeled fibers in the lesion cases (c and d) vs. the control cases (a and b) (TIF 19233 KB)

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Hormigo, S., López, D.E., Cardoso, A. et al. Direct and indirect nigrofugal projections to the nucleus reticularis pontis caudalis mediate in the motor execution of the acoustic startle reflex. Brain Struct Funct 223, 2733–2751 (2018). https://doi.org/10.1007/s00429-018-1654-9

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  • DOI: https://doi.org/10.1007/s00429-018-1654-9

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