Brain Structure and Function

, Volume 223, Issue 6, pp 2733–2751 | Cite as

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

  • Sebastian Hormigo
  • Dolores E. López
  • Antonio Cardoso
  • Gladys Zapata
  • Jacqueline Sepúlveda
  • Orlando CastellanoEmail author
Original Article


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.


Arginine Aspartate Cochlear root neurons Dopamine GABA Glutamate Motor response Pedunculopontine tegmental nucleus Somatosensory gating Substantia nigra 





Avidin-biotin-peroxidase complex






Acoustic startle reflex


Biotinylated dextran amine




Capillary electrophoresis laser-induced fluorescence detection


Cochlear root neurons


Cerebellar peduncle




γ-Aminobutyric acid




Globus pallidus


Inferior colliculus








Trochlear nucleus


Lateral lemniscus


Molecular weight


Periaqueductal grey


Phosphate buffer


Nucleus reticularis pontis caudalis


Oral pontine reticular nucleus


Pedunculopontine tegmental nucleus


Superior colliculus


Substantia nigra


Substantia nigra pars compacta


Substantia nigra pars reticulata


Superior olivary complex


Tyrosine-hydroxylase immunoreactivity


Facial nerve


Auditory-vestibular nerve


Ventral tegmental area


Cerebellar peduncle, decussation



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.

Compliance with ethical standards

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.

Supplementary material

429_2018_1654_MOESM1_ESM.tif (18.8 mb)
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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© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute for Neuroscience of Castilla y León (INCYL)University of SalamancaSalamancaSpain
  2. 2.Institute of Biomedical Research of Salamanca (IBSAL)University of SalamancaSalamancaSpain
  3. 3.Department of Cell Biology and PathologyUniversity of SalamancaSalamancaSpain
  4. 4.Department of Nursing and Physical TherapyUniversity of SalamancaSalamancaSpain
  5. 5.Department of Pharmacology, Faculty of Biological SciencesUniversity of ConcepciónConcepciónChile

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