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 Castellano
Original Article
  • 86 Downloads

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.

Keywords

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

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

Notes

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.

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)

References

  1. Aaron RV, Benning SD (2016) Postauricular reflexes elicited by soft acoustic clicks and loud noise probes: reliability, prepulse facilitation, and sensitivity to picture contents. Psychophysiology 53(12):1900–1908.  https://doi.org/10.1111/psyp.12757 (Epub 2016 Sep 6) PubMedPubMedCentralCrossRefGoogle Scholar
  2. Aitken P, Zheng Y, Smith PF (2017) Effects of bilateral vestibular deafferentation in rat on hippocampal theta response to somatosensory stimulation, acetylcholine release, and cholinergic neurons in the pedunculopontine tegmental nucleus. Brain Struct Funct.  https://doi.org/10.1007/s00429-017-1407-1 (Epub ahead of print) PubMedGoogle Scholar
  3. Albin RL, Young AB, Penney JB (1989) The functional anatomy of basal ganglia disorders. Trends Neurosci 12(10):366–375 (Review) PubMedCrossRefGoogle Scholar
  4. Borst C, Belal F, Holzgrabe U (2013) Possibilities and limitations of capillary electrophoresis in pharmaceutical analysis. Pharmazie 68(7):526–530PubMedGoogle Scholar
  5. Bosch D, Schmid S (2006) Activation of muscarinic cholinergic receptors inhibits giant neurones in the caudal pontine reticular nucleus. Eur J Neurosci 24(7):1967–1975 (Epub 2006 Oct 16) PubMedCrossRefGoogle Scholar
  6. Brown J, Pan WX, Dudman JT (2014) The inhibitory microcircuit of the substantia nigra provides feedback gain control of the basal ganglia output. Elife 3:e02397.  https://doi.org/10.7554/eLife.02397 PubMedPubMedCentralGoogle Scholar
  7. Buonamici M, Cervini MA, Rossi AC, Sebastiani L, Raffaelli A, Bagnoli P (1990) Injections of 6-hydroxydopamine in the substantia nigra of the rat brain: morphological and biochemical effects. Behav Brain Res 38(1):83–95PubMedCrossRefGoogle Scholar
  8. Carey RJ (1986) Relationship of changes in spontaneous motor activity to spontaneous circling in rats with unilateral 6-hydroxydopamine lesions of the substantia nigra. Exp Neurol 92(3):591–600PubMedCrossRefGoogle Scholar
  9. Castellano O, Moscoso A, Riolobos AS, Carro J, Arji M, Molina V, López DE, Sancho C (2009) Chronic administration of risperidone to healthy rats: a behavioural and morphological study. Behav Brain Res 205(2):488–498.  https://doi.org/10.1016/j.bbr.2009.08.002 (Epub 2009 Aug 7) PubMedCrossRefGoogle Scholar
  10. Cui G, Jun SB, Jin X, Pham MD, Vogel SS, Lovinger DM, Costa RM (2013) Concurrent activation of striatal direct and indirect pathways during action initiation. Nature 494(7436):238–242.  https://doi.org/10.1038/nature11846 (Epub 2013 Jan 23) PubMedPubMedCentralCrossRefGoogle Scholar
  11. Czech DP, Lee J, Correia J, Loke H, Möller EK, Harley VR (2014) Transient neuroprotection by SRY upregulation in dopamine cells following injury in males. Endocrinology 155(7):2602–2612.  https://doi.org/10.1210/en.2013-2158 (Epub 2014 Apr 7) PubMedCrossRefGoogle Scholar
  12. Davis M (1990) Animal models of anxiety based on classical conditioning: the conditioned emotional response (CER) and the fear-potentiated startle effect. Pharmacol Ther 47(2):147–165 (Review) PubMedCrossRefGoogle Scholar
  13. Davis M (1992) The role of the amygdala in fear-potentiated startle: implications for animal models of anxiety. Trends Pharmacol Sci 13(1):35–41 (Review) PubMedCrossRefGoogle Scholar
  14. Di Chiara G, Morelli M, Porceddu ML, Gessa GL (1979) Role of thalamic gamma-aminobutyrate in motor functions: catalepsy and ipsiversive turning after intrathalamic muscimol. Neuroscience 4(10):1453–1465PubMedCrossRefGoogle Scholar
  15. Ebert U, Koch M (1992) Glutamate receptors mediate acoustic input to the reticular brain stem. Neuroreport 3(5):429–432PubMedCrossRefGoogle Scholar
  16. Fendt M, Koch M (1999) Cholinergic modulation of the acoustic startle response in the caudal pontine reticular nucleus of the rat. Eur J Pharmacol 370(2):101–107PubMedCrossRefGoogle Scholar
  17. Ford B, Holmes CJ, Mainville L, Jones BE (1995) GABAergic neurons in the rat pontomesencephalic tegmentum: codistribution with cholinergic and other tegmental neurons projecting to the posterior lateral hypothalamus. J Comp Neurol 363(2):177–196PubMedCrossRefGoogle Scholar
  18. Freeze BS, Kravitz AV, Hammack N, Berke JD, Kreitzer AC (2013) Control of basal ganglia output by direct and indirect pathway projection neurons. J Neurosci 33(47):18531–18539.  https://doi.org/10.1523/JNEUROSCI.1278-13.2013 PubMedPubMedCentralCrossRefGoogle Scholar
  19. Fujimura H, Umbach I (1987) Role of the involvement of the reticular formation in the dementia of Parkinson’s disease. Rev Neurol (Paris) 143(2):108–114 (French) Google Scholar
  20. Fukushima K (1991) The interstitial nucleus of Cajal in the midbrain reticular formation and vertical eye movement. Neurosci Res 10(3):159–187 (Review) PubMedCrossRefGoogle Scholar
  21. Gambardella S, Ferese R, Biagioni F, Busceti CL, Campopiano R, Griguoli AMP, Limanaqi F, Novelli G, Storto M, Fornai F (2017) The Monoamine brainstem reticular formation as a paradigm for re-defining various phenotypes of Parkinson’s disease owing genetic and anatomical specificity. Front Cell Neurosci 11:102.  https://doi.org/10.3389/fncel.2017.00102 (eCollection 2017. Review) PubMedPubMedCentralCrossRefGoogle Scholar
  22. Garcia-Rill E (1991) The pedunculopontine nucleus. Prog Neurobiol 36(5):363–389 (Review) PubMedCrossRefGoogle Scholar
  23. Goetz L, Piallat B, Bhattacharjee M, Mathieu H, David O, Chabardès S (2016) On the role of the pedunculopontine nucleus and mesencephalic reticular formation in locomotion in nonhuman primates. J Neurosci 36(18):4917–4929.  https://doi.org/10.1523/JNEUROSCI.2514-15.2016 PubMedCrossRefGoogle Scholar
  24. Gómez-Nieto R, Horta-Júnior Jde A, Castellano O, Millian-Morell L, Rubio ME, López DE (2014a) Origin and function of short-latency inputs to the neural substrates underlying the acoustic startle reflex. Front Neurosci 8:216.  https://doi.org/10.3389/fnins.2014.00216 (eCollection 2014)PubMedPubMedCentralGoogle Scholar
  25. Gómez-Nieto R, Sinex DG, Horta-Júnior Jde A, Castellano O, Herrero-Turrión JM, López DE (2014b) A fast cholinergic modulation of the primary acoustic startle circuit in rats. Brain Struct Funct 219(5):1555–1573.  https://doi.org/10.1007/s00429-013-0585-8 (Epub 2013 Jun 4) PubMedGoogle Scholar
  26. Granata AR, Kitai ST (1991) Inhibitory substantia nigra inputs to the pedunculopontine neurons. Exp Brain Res 86(3):459–466PubMedCrossRefGoogle Scholar
  27. Gulcebi MI, Ketenci S, Linke R, Hacıoğlu H, Yanalı H, Veliskova J, Moshé SL, Onat F, Çavdar S (2012) Topographical connections of the substantia nigra pars reticulata to higher-order thalamic nuclei in the rat. Brain Res Bull 87(2–3):312–318.  https://doi.org/10.1016/j.brainresbull.2011.11.005 (Epub 2011 Nov 17) PubMedCrossRefGoogle Scholar
  28. Gundersen HJ (1986) Stereology of arbitrary particles. A review of unbiased number and size estimators and the presentation of some new ones, in memory of William R. Thompson. J Microsc 143(Pt 1):3–45PubMedCrossRefGoogle Scholar
  29. Gurney K, Prescott TJ, Redgrave P (2001) A computational model of action selection in the basal ganglia. II. Analysis and simulation of behaviour. Biol Cybern 84(6):411–423PubMedCrossRefGoogle Scholar
  30. Hackley SA, Ren X, Underwood A, Valle-Inclán F (2017) Prepulse inhibition and facilitation of the postauricular reflex, a vestigial remnant of pinna startle. Psychophysiology 54(4):566–577.  https://doi.org/10.1111/psyp.12819 (Epub 2017 Feb 7) PubMedCrossRefGoogle Scholar
  31. He ZG, Liu BW, Li ZX, Tian XB, Liu SG, Manyande A, Zhang DY, Xiang HB (2017) The caudal pedunculopontine tegmental nucleus may be involved in the regulation of skeletal muscle activity by melanocortinsympathetic pathway: a virally mediated trans-synaptic tracing study in spinally transected transgenic mice. Oncotarget.  https://doi.org/10.18632/oncotarget.17983 (Epub ahead of print) Google Scholar
  32. Hernández L, Escalona J, Joshi N, Guzmán N (1991) A laser-induced fluorescence and fluorescence microscopy for capillary electrophoresis zone detection. J Chromatogr A 559(1–2):183–196.  https://doi.org/10.1016/0021-9673(91)80069-S CrossRefGoogle Scholar
  33. Hikida T, Kimura K, Wada N, Funabiki K, Nakanishi S (2010) Distinct roles of synaptic transmission in direct and indirect striatal pathways to reward and aversive behavior. Neuron 66(6):896–907.  https://doi.org/10.1016/j.neuron.2010.05.011 PubMedCrossRefGoogle Scholar
  34. Hirsch EC, Höglinger G, Rousselet E, Breidert T, Parain K, Feger J, Ruberg M, Prigent A, Cohen-Salmon C, Launay JM (2003) Animal models of Parkinson’s disease in rodents induced by toxins: an update. J Neural Transm Suppl 65:89–100 (Review) CrossRefGoogle Scholar
  35. Höglinger GU, Carrard G, Michel PP, Medja F, Lombès A, Ruberg M, Friguet B, Hirsch EC (2003) Dysfunction of mitochondrial complex I and the proteasome: interactions between two biochemical deficits in a cellular model of Parkinson’s disease. J Neurochem 86(5):1297–1307PubMedCrossRefGoogle Scholar
  36. Hökfelt T, Ungerstedt U (1973) Specificity of 6-hydroxydopamine induced degeneration of central monoamine neurones: an electron and fluorescence microscopic study with special reference to intracerebral injection on the nigro-striatal dopamine system. Brain Res 60(2):269–297PubMedCrossRefGoogle Scholar
  37. Honda T, Semba K (1995) An ultrastructural study of cholinergic and non-cholinergic neurons in the laterodorsal and pedunculopontine tegmental nuclei in the rat. Neuroscience 68(3):837–853PubMedCrossRefGoogle Scholar
  38. Hoover JE, Strick PL (1993) Multiple output channels in the basal ganglia. Science 259(5096):819–821PubMedCrossRefGoogle Scholar
  39. Hormigo S, Horta Júnior Jde A, Gómez-Nieto R, López DE (2012) The selective neurotoxin DSP-4 impairs the noradrenergic projections from the locus coeruleus to the inferior colliculus in rats. Front Neural Circuits 6:41.  https://doi.org/10.3389/fncir.2012.00041 (eCollection 2012) PubMedPubMedCentralCrossRefGoogle Scholar
  40. Hormigo S, Gómez-Nieto R, Castellano O, Herrero-Turrión MJ, López DE, de Anchieta de Castro E, Horta-Júnior J (2015) The noradrenergic projection from the locus coeruleus to the cochlear root neurons in rats. Brain Struct Funct 220(3):1477–1496.  https://doi.org/10.1007/s00429-014-0739-3 (Epub 2014 Mar 13) PubMedCrossRefGoogle Scholar
  41. Hormigo S, Vega-Flores G, Castro-Alamancos MA (2016) Basal ganglia output controls active avoidance behavior. J Neurosci 36(40):10274–10284PubMedPubMedCentralCrossRefGoogle Scholar
  42. Hormigo S, Gómez-Nieto R, Sancho C, Herrero-Turrión J, Carro J, López DE, Horta-Júnior JA (2017) Morphological correlates of sex differences in acoustic startle response and prepulse inhibition through projections from locus coeruleus to cochlear root neurons. Brain Struct Funct.  https://doi.org/10.1007/s00429-017-1415-1 (Epub ahead of print) PubMedGoogle Scholar
  43. Hossain MA, Weiner N (1995) Interactions of dopaminergic and GABAergic neurotransmission: impact of 6-hydroxydopamine lesions into the substantia nigra of rats. J Pharmacol Exp Ther 275(1):237–244PubMedGoogle Scholar
  44. Jeon BS, Jackson-Lewis V, Burke RE (1995) 6-Hydroxydopamine lesion of the rat substantia nigra: time course and morphology of cell death. Neurodegeneration 4(2):131–137PubMedCrossRefGoogle Scholar
  45. Kang Y, Kitai ST (1990) Electrophysiological properties of pedunculopontine neurons and their postsynaptic responses following stimulation of substantia nigra reticulata. Brain Res 535(1):79–95PubMedCrossRefGoogle Scholar
  46. Keay KA, Redgrave P, Dean P (1988) Cardiovascular and respiratory changes elicited by stimulation of rat superior colliculus. Brain Res Bull 20(1):13–26PubMedCrossRefGoogle Scholar
  47. Koch M (1999) The neurobiology of startle. Prog Neurobiol 59(2):107–128 (Review) PubMedCrossRefGoogle Scholar
  48. Koch M, Ebert U (1993) Enhancement of the acoustic startle response by stimulation of an excitatory pathway from the central amygdala/basal nucleus of Meynert to the pontine reticular formation. Exp Brain Res 93(2):231–241PubMedCrossRefGoogle Scholar
  49. Koch M, Schnitzler HU (1997) The acoustic startle response in rats-circuits mediating evocation, inhibition and potentiation. Behav Brain Res 89(1–2):35–49 (Review) PubMedCrossRefGoogle Scholar
  50. Koch M, Kungel M, Herbert H (1993) Cholinergic neurons in the pedunculopontine tegmental nucleus are involved in the mediation of prepulse inhibition of the acoustic startle response in the rat. Exp Brain Res 97(1):71–82PubMedCrossRefGoogle Scholar
  51. Krase W, Koch M, Schnitzler HU (1993) Glutamate antagonists in the reticular formation reduce the acoustic startle response. Neuroreport 4(1):13–16PubMedCrossRefGoogle Scholar
  52. Kravitz AV, Kreitzer AC (2012) Striatal mechanisms underlying movement, reinforcement, and punishment. Physiology (Bethesda) 27(3):167–177.  https://doi.org/10.1152/physiol.00004.2012 (Review) Google Scholar
  53. Kravitz AV, Freeze BS, Parker PR, Kay K, Thwin MT, Deisseroth K, Kreitzer AC (2010) Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry. Nature 466(7306):622–626.  https://doi.org/10.1038/nature09159 (Epub 2010 Jul 7) PubMedPubMedCentralCrossRefGoogle Scholar
  54. Kumari V, Hamid A, Brand A, Antonova E (2015) Acoustic prepulse inhibition: one ear is better than two, but why and when? Psychophysiology 52(5):714–721.  https://doi.org/10.1111/psyp.12391 (Epub 2014 Dec 5) PubMedCrossRefGoogle Scholar
  55. Lavoie B, Parent A (1994a) Pedunculopontine nucleus in the squirrel monkey: cholinergic and glutamatergic projections to the substantia nigra. J Comp Neurol 344(2):232–241PubMedCrossRefGoogle Scholar
  56. Lavoie B, Parent A (1994b) Pedunculopontine nucleus in the squirrel monkey: distribution of cholinergic and monoaminergic neurons in the mesopontine tegmentum with evidence for the presence of glutamate in cholinergic neurons. J Comp Neurol 344(2):190–209PubMedCrossRefGoogle Scholar
  57. Lee Y, López DE, Meloni EG, Davis M (1996) A primary acoustic startle pathway: obligatory role of cochlear root neurons and the nucleus reticularis pontis caudalis. J Neurosci 16(11):3775–3789PubMedGoogle Scholar
  58. Mandel S, Grünblatt E, Riederer P, Youdim MB (2003) Genes and oxidative stress in parkinsonism: cDNA microarray studies. Adv Neurol 91:123–132 (Review)Google Scholar
  59. Meesarapee B, Thampithak A, Jaisin Y, Sanvarinda P, Suksamrarn A, Tuchinda P, Morales NP, Sanvarinda Y (2014) Curcumin I mediates neuroprotective effect through attenuation of quinoprotein formation, p-p38 MAPK expression, and caspase-3 activation in 6-hydroxydopamine treated SH-SY5Y cells. Phytother Res 28(4):611–616.  https://doi.org/10.1002/ptr.5036 (Epub 2013 Jul 16) PubMedCrossRefGoogle Scholar
  60. Mendez JS, Finn BW (1975) Use of 6-hydroxydopamine to create lesions in catecholamine neurons in rats. J Neurosurg 42(2):166–173PubMedCrossRefGoogle Scholar
  61. Mesulam MM, Mufson EJ, Levey AI, Wainer BH (1983) Cholinergic innervation of cortex by the basal forebrain: cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (substantia innominata), and hypothalamus in the rhesus monkey. J Comp Neurol 214(2):170–197PubMedCrossRefGoogle Scholar
  62. Mesulam MM, Geula C, Bothwell MA, Hersh LB (1989) Human reticular formation: cholinergic neurons of the pedunculopontine and laterodorsal tegmental nuclei and some cytochemical comparisons to forebrain cholinergic neurons. J Comp Neurol 283(4):611–633PubMedCrossRefGoogle Scholar
  63. Mink JW (1996) The basal ganglia: focused selection and inhibition of competing motor programs. Prog Neurobiol 50(4):381–425 (Review)PubMedCrossRefGoogle Scholar
  64. Nair-Roberts RG, Chatelain-Badie SD, Benson E, White-Cooper H, Bolam JP, Ungless MA (2008) Stereological estimates of dopaminergic, GABAergic and glutamatergic neurons in the ventral tegmental area, substantia nigra and retrorubral field in the rat. Neuroscience 152(4):1024–1031.  https://doi.org/10.1016/j.neuroscience.2008.01.046 (Epub 2008 Feb 7) PubMedPubMedCentralCrossRefGoogle Scholar
  65. Naoi M, Maruyama W (2001) Future of neuroprotection in Parkinson’s disease. Parkinsonism Relat Disord 8(2):139–145PubMedCrossRefGoogle Scholar
  66. Noda T, Oka H (1986) Distribution and morphology of tegmental neurons receiving nigral inhibitory inputs in the cat: an intracellular HRP study. J Comp Neurol 244(2):254–266PubMedCrossRefGoogle Scholar
  67. Nodal FR, López DE (2003) Direct input from cochlear root neurons to pontine reticulospinal neurons in albino rat. J Comp Neurol 460(1):80–93PubMedCrossRefGoogle Scholar
  68. Pahapill PA, Lozano AM (2000) The pedunculopontine nucleus and Parkinson’s disease. Brain 123(Pt 9):1767–1783 (Review) Google Scholar
  69. Paxinos G, Watson C (2005) The rat brain in stereotaxic coordinates: the new coronal set—161 diagrams, 5th edn. Academic, San DiegoGoogle Scholar
  70. Pilati N, Barker M, Panteleimonitis S, Donga R, Hamann M (2008) A rapid method combining Golgi and Nissl staining to study neuronal morphology and cytoarchitecture. J Histochem Cytochem 56(6):539–550.  https://doi.org/10.1369/jhc.2008.950246 (Epub 2008 Feb 18) PubMedPubMedCentralCrossRefGoogle Scholar
  71. Redgrave P, Prescott TJ, Gurney K (1999) The basal ganglia: a vertebrate solution to the selection problem? Neuroscience 89(4):1009–1023 (Review) PubMedCrossRefGoogle Scholar
  72. Romanelli P, Esposito V, Schaal DW, Heit G (2005) Somatotopy in the basal ganglia: experimental and clinical evidence for segregated sensorimotor channels. Brain Res Brain Res Rev 48(1):112–128 (Review) PubMedCrossRefGoogle Scholar
  73. Rye DB, Saper CB, Lee HJ, Wainer BH (1987) Pedunculopontine tegmental nucleus of the rat: cytoarchitecture, cytochemistry, and some extrapyramidal connections of the mesopontine tegmentum. J Comp Neurol 259(4):483–528PubMedCrossRefGoogle Scholar
  74. Saint-Cyr JA (2003) Frontal-striatal circuit functions: context, sequence, and consequence. J Int Neuropsychol Soc 9(1):103–127 (Review Erratum in: J Int Neuropsychol Soc. 2003 Mar;9(3):502) PubMedCrossRefGoogle Scholar
  75. Saitoh K, Hattori S, Song WJ, Isa T, Takakusaki K (2003) Nigral GABAergic inhibition upon cholinergic neurons in the rat pedunculopontine tegmental nucleus. Eur J Neurosci 18(4):879–886PubMedCrossRefGoogle Scholar
  76. Sakai K, Gash DM (1994) Effect of bilateral 6-OHDA lesions of the substantia nigra on locomotor activity in the rat. Brain Res 633(1–2):144–150PubMedCrossRefGoogle Scholar
  77. Schmid S, Wilson DA, Rankin CH (2015) Habituation mechanisms and their importance for cognitive function. Front Integr Neurosci 8:97.  https://doi.org/10.3389/fnint.2014.00097 (eCollection 2014) PubMedPubMedCentralCrossRefGoogle Scholar
  78. Sepúlveda J, Oliva P, Contreras E (2004) Neurochemical changes of the extracellular concentrations of glutamate and aspartate in the nucleus accumbens of rats after chronic administration of morphine. Eur J Pharmacol 483(2–3):249–258PubMedCrossRefGoogle Scholar
  79. Shaikh KT, Yang A, Youshin E, Schmid S (2015) Transgenic LRRK2 (R1441G) rats—a model for Parkinson disease? PeerJ 3:e945.  https://doi.org/10.7717/peerj.945 (eCollection 2015)PubMedPubMedCentralCrossRefGoogle Scholar
  80. Silkis I (2001) The cortico-basal ganglia-thalamocortical circuit with synaptic plasticity. II. Mechanism of synergistic modulation of thalamic activity via the direct and indirect pathways through the basal ganglia. Biosystems 59(1):7–14 (Review) PubMedCrossRefGoogle Scholar
  81. Smith Y, Bolam JP (1990) The output neurones and the dopaminergic neurones of the substantia nigra receive a GABA-containing input from the globus pallidus in the rat. J Comp Neurol 296(1):47–64PubMedCrossRefGoogle Scholar
  82. Smith Y, Villalba R (2008) Striatal and extrastriatal dopamine in the basal ganglia: an overview of its anatomical organization in normal and Parkinsonian brains. Mov Disord 23(Suppl 3):S534–S547.  https://doi.org/10.1002/mds.22027 (Review) PubMedCrossRefGoogle Scholar
  83. Smith Y, Bevan MD, Shink E, Bolam JP (1998) Microcircuitry of the direct and indirect pathways of the basal ganglia. Neuroscience 86(2):353–387 (Review) PubMedCrossRefGoogle Scholar
  84. Smith Y, Raju D, Nanda B, Pare JF, Galvan A, Wichmann T (2009) The thalamostriatal systems: anatomical and functional organization in normal and parkinsonian states. Brain Res Bull 78(2–3):60–68.  https://doi.org/10.1016/j.brainresbull.2008.08.015 (Epub 2008 Sep 19. Review) Google Scholar
  85. Swerdlow NR, Geyer MA (1998) Using an animal model of deficient sensorimotor gating to study the pathophysiology and new treatments of schizophrenia. Schizophr Bull 24(2):285–301 (Review) PubMedCrossRefGoogle Scholar
  86. Takakusaki K, Shiroyama T, Yamamoto T, Kitai ST (1996) Cholinergic and noncholinergic tegmental pedunculopontine projection neurons in rats revealed by intracellular labeling. J Comp Neurol 371(3):345–361PubMedCrossRefGoogle Scholar
  87. Takakusaki K, Obara K, Nozu T, Okumura T (2011) Modulatory effects of the GABAergic basal ganglia neurons on the PPN and the muscle tone inhibitory system in cats. Arch Ital Biol 149(4):385–405.  https://doi.org/10.4449/aib.v149i4.1383 (Epub 2011 Dec 1) PubMedGoogle Scholar
  88. Tecuapetla F, Matias S, Dugue GP, Mainen ZF, Costa RM (2014) Balanced activity in basal ganglia projection pathways is critical for contraversive movements. Nat Commun 5:4315.  https://doi.org/10.1038/ncomms5315 PubMedPubMedCentralCrossRefGoogle Scholar
  89. Tye KM, Deisseroth K (2012) Optogenetic investigation of neural circuits underlying brain disease in animal models. Nat Rev Neurosci 13(4):251–266.  https://doi.org/10.1038/nrn3171 (Review) PubMedCrossRefGoogle Scholar
  90. Ungerstedt U (1971) Striatal dopamine release after amphetamine or nerve degeneration revealed by rotational behaviour. Acta Physiol Scand Suppl 367:49–68PubMedCrossRefGoogle Scholar
  91. Ungerstedt U, Ljungberg T, Steg G (1974) Behavioral, physiological, and neurochemical changes after 6-hydroxydopamine-induced degeneration of the nigro-striatal dopamine neurons. Adv Neurol 5:421–426PubMedGoogle Scholar
  92. Valsamis B, Schmid S (2011) Habituation and prepulse inhibition of acoustic startle in rodents. J Vis Exp 55:e3446.  https://doi.org/10.3791/3446 Google Scholar
  93. Wang HL, Morales M (2009) Pedunculopontine and laterodorsal tegmental nuclei contain distinct populations of cholinergic, glutamatergic and GABAergic neurons in the rat. Eur J Neurosci 29(2):340–358.  https://doi.org/10.1111/j.1460-9568.2008.06576.x PubMedCrossRefGoogle Scholar
  94. West MJ, Slomianka L, Gundersen HJ (1991) Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator. Anat Rec 231(4):482–497PubMedCrossRefGoogle Scholar
  95. Willis GL, Kennedy GA (2004) The implementation of acute versus chronic animal models for treatment discovery in Parkinson’s disease. Rev Neurosci 15(1):75–87 (Review) PubMedCrossRefGoogle Scholar
  96. Wilson VJ (1993) Vestibulospinal reflexes and the reticular formation. Prog Brain Res 97:211–217 (Review) PubMedCrossRefGoogle Scholar
  97. Yamaguchi T, Wang HL, Morales M (2013) Glutamate neurons in the substantia nigra compacta and retrorubral field. Eur J Neurosci 38(11):3602–3610.  https://doi.org/10.1111/ejn.12359 (Epub 2013 Sep 16) PubMedPubMedCentralCrossRefGoogle Scholar
  98. Yeomans JS, Frankland PW (1995) The acoustic startle reflex: neurons and connections. Brain Res Brain Res Rev 21(3):301–314 (Review) PubMedCrossRefGoogle Scholar
  99. Yeomans JS, Li L, Scott BW, Frankland PW (2002) Tactile, acoustic and vestibular systems sum to elicit the startle reflex. Neurosci Biobehav Rev 26(1):1–11 (Review) PubMedCrossRefGoogle Scholar
  100. Yoo JH, Zell V, Wu J, Punta C, Ramajayam N, Shen X, Faget L, Lilascharoen V, Lim BK, Hnasko TS (2017) Activation of Pedunculopontine glutamate neurons is reinforcing. J Neurosci 37(1):38–46.  https://doi.org/10.1523/JNEUROSCI.3082-16.2016 PubMedPubMedCentralCrossRefGoogle Scholar
  101. Young HM, Furness JB, Shuttleworth CW, Bredt DS, Snyder SH (1992) Co-localization of nitric oxide synthase immunoreactivity and NADPH diaphorase staining in neurons of the guinea-pig intestine. Histochemistry 97(4):375–378PubMedCrossRefGoogle Scholar
  102. Zhao Z, Davis M (2004) Fear-potentiated startle in rats is mediated by neurons in the deep layers of the superior colliculus/deep mesencephalic nucleus of the rostral midbrain through the glutamate non-NMDA receptors. J Neurosci 24(46):10326–10334PubMedCrossRefGoogle Scholar
  103. Zhu Y, Liu F, Zou X, Torbey M. Comparison of unbiased estimation of neuronal number in the rat hippocampus with different staining methods. J Neurosci Methods. 2015;254:73–79.  https://doi.org/10.1016/j.jneumeth.2015.07.022 (Epub 2015 Jul 31) CrossRefGoogle Scholar

Copyright information

© 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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