Advertisement

Brain Structure and Function

, Volume 220, Issue 5, pp 2739–2763 | Cite as

Localisation and stress-induced plasticity of GABAA receptor subunits within the cellular networks of the mouse dorsal raphe nucleus

  • Nicole L. Corteen
  • Jessica A. Carter
  • Uwe Rudolph
  • Delia Belelli
  • Jeremy J. Lambert
  • Jerome D. SwinnyEmail author
Original Article

Abstract

The dorsal raphe nucleus (DRN) provides the major source of serotonin to the central nervous system (CNS) and modulates diverse neural functions including mood. Furthermore, DRN cellular networks are engaged in the stress–response at the CNS level allowing for adaptive behavioural responses, whilst stress-induced dysregulation of DRN and serotonin release is implicated in psychiatric disorders. Therefore, identifying the molecules regulating DRN activity is fundamental to understand DRN function in health and disease. GABAA receptors (GABAARs) allow for brain region, cell type and subcellular domain-specific GABA-mediated inhibitory currents and are thus key regulators of neuronal activity. Yet, the GABAAR subtypes expressed within the neurochemically diverse cell types of the mouse DRN are poorly described. In this study, immunohistochemistry and confocal microscopy revealed that all serotonergic neurons expressed immunoreactivity for the GABAAR alpha2 and 3 subunits, although the respective signals were co-localised to varying degrees with inhibitory synaptic marker proteins. Only a topographically located sub-population of serotonergic neurons exhibited GABAAR alpha1 subunit immunoreactivity. However, all GABAergic as well as non-GABAergic, non-serotonergic neurons within the DRN expressed GABAAR alpha1 subunit immunoreactivity. Intriguingly, immunoreactivity for the GABAAR gamma2 subunit was enriched on GABAergic rather than serotonergic neurons. Finally, repeated restraint stress increased the expression of the GABAAR alpha3 subunit at the mRNA and protein level. The study demonstrates the identity and location of distinct GABAAR subunits within the cellular networks of the mouse DRN and that stress impacts on the expression levels of particular subunits at the gene and protein level.

Keywords

Serotonin Immunohistochemistry Anxiety Benzodiazepine Depression 

Notes

Acknowledgments

We are extremely grateful to Professors Jean-Marc Fritschy and Werner Sieghart for the generous supply of antibodies against the various GABAAR subunits. We are also sincerely grateful to Scott Rodaway and Angela Scutt for their expert technical assistance.

References

  1. Abramian AM, Comenencia-Ortiz E, Modgil A, Vien TN, Nakamura Y, Moore YE, Maguire JL, Terunuma M, Davies PA, Moss SJ (2014) Neurosteroids promote phosphorylation and membrane insertion of extrasynaptic GABAA receptors. Proc Natl Acad Sci USA 111(19):7132–7137. doi: 10.1073/pnas.1403285111 PubMedCentralCrossRefPubMedGoogle Scholar
  2. Adell A, Casanovas JM, Artigas F (1997) Comparative Study in the rat of the actions of different types of stress on the release of 5-HT in raphe Nuclei and Forebrain Areas. Neuropharmacology 36(4–5):735–741. doi: 10.1016/S0028-3908(97)00048-8 CrossRefPubMedGoogle Scholar
  3. Aronsson M, Fuxe K, Dong Y, Agnati LF, Okret S, Gustafsson J-A (1988) Localization of glucocorticoid receptor mRNA in the male rat brain by in situ hybridization. Proc Natl Acad Sci 85(23):9331–9335PubMedCentralCrossRefPubMedGoogle Scholar
  4. Bang SJ, Commons KG (2012) Forebrain GABAergic projections from the dorsal raphe nucleus identified by using GAD67-GFP knock-in mice. J Comp Neurol 520(18):4157–4167. doi: 10.1002/cne.23146 PubMedCentralCrossRefPubMedGoogle Scholar
  5. Baumann B, Bielau H, Krell D, Agelink M, Diekmann S, Wurthmann C, Trubner K, Bernstein H, Danos P, Bogerts B (2002) Circumscribed numerical deficit of dorsal raphe neurons in mood disorders. Psychol Med 32(1):93–103CrossRefPubMedGoogle Scholar
  6. Belelli D, Harrison NL, Maguire J, Macdonald RL, Walker MC, Cope DW (2009) Extrasynaptic GABAA receptors: form, pharmacology, and function. J Neurosci 29(41):12757–12763. doi: 10.1523/JNEUROSCI.3340-09.2009 PubMedCentralCrossRefPubMedGoogle Scholar
  7. Benson JA, Low K, Keist R, Mohler H, Rudolph U (1998) Pharmacology of recombinant gamma-aminobutyric acidA receptors rendered diazepam-insensitive by point-mutated alpha-subunits. FEBS Lett 431(3):400–404CrossRefPubMedGoogle Scholar
  8. Binder EB, Nemeroff CB (2010) The CRF system, stress, depression and anxiety-insights from human genetic studies. Mol Psychiatry 15(6):574–588. doi: 10.1038/mp.2009.141 PubMedCentralCrossRefPubMedGoogle Scholar
  9. Browne SH, Kang J, Akk G, Chiang LW, Schulman H, Huguenard JR, Prince DA (2001) Kinetic and pharmacological properties of GABAAReceptors in single thalamic neurons and GABAA subunit expression. J Neurophysiol 86(5):2312–2322PubMedGoogle Scholar
  10. Buynitsky T, Mostofsky DI (2009) Restraint stress in biobehavioral research: recent developments. Neurosci Biobehav Rev 33(7):1089–1098. doi: 10.1016/j.neubiorev.2009.05.004 CrossRefPubMedGoogle Scholar
  11. Carter JA, Górecki DC, Mein CA, Ljungberg B, Hafizi S (2013) CpG dinucleotide-specific hypermethylation of the TNS3 gene promoter in human renal cell carcinoma. Epigenetics 8(7):739–747PubMedCentralCrossRefPubMedGoogle Scholar
  12. Celada P, Puig MV, Casanovas JM, Guillazo G, Artigas F (2001) Control of dorsal raphe serotonergic neurons by the medial prefrontal cortex: involvement of serotonin-1A, GABA(A), and glutamate receptors. J Neurosci 21(24):9917–9929PubMedGoogle Scholar
  13. Challis C, Boulden J, Veerakumar A, Espallergues J, Vassoler FM, Pierce RC, Beck SG, Berton O (2013) Raphe GABAergic neurons mediate the acquisition of avoidance after social defeat. J Neurosci 33(35):13978–13988. doi: 10.1523/JNEUROSCI.2383-13.2013 PubMedCentralCrossRefPubMedGoogle Scholar
  14. Corteen NL, Cole TM, Sarna A, Sieghart W, Swinny JD (2011) Localization of GABA-A receptor alpha subunits on neurochemically distinct cell types in the rat locus coeruleus. Eur J Neurosci 34(2):250–262. doi: 10.1111/j.1460-9568.2011.07740.x CrossRefPubMedGoogle Scholar
  15. Crawford LK, Rahman SF, Beck SG (2013) Social stress alters inhibitory synaptic input to distinct subpopulations of raphe serotonin neurons. ACS chemical neuroscience 4(1):200–209. doi: 10.1021/cn300238j PubMedCentralCrossRefPubMedGoogle Scholar
  16. Crestani F, Lorez M, Baer K, Essrich C, Benke D, Laurent JP, Belzung C, Fritschy J-M, Lüscher B, Mohler H (1999) Decreased GABAA-receptor clustering results in enhanced anxiety and a bias for threat cues. Nat Neurosci 2(9):833–839. doi: 10.1038/12207 CrossRefPubMedGoogle Scholar
  17. Dixon CI, Rosahl TW, Stephens DN (2008) Targeted deletion of the GABRA2 gene encoding alpha2-subunits of GABA(A) receptors facilitates performance of a conditioned emotional response, and abolishes anxiolytic effects of benzodiazepines and barbiturates. Pharmacol Biochem Behav 90(1):1–8. doi: 10.1016/j.pbb.2008.01.015 CrossRefPubMedGoogle Scholar
  18. Engin E, Liu J, Rudolph U (2012) Alpha2-containing GABA(A) receptors: a target for the development of novel treatment strategies for CNS disorders. Pharmacol Ther 136(2):142–152. doi: 10.1016/j.pharmthera.2012.08.006 PubMedCentralCrossRefPubMedGoogle Scholar
  19. Essrich C, Lorez M, Benson JA, Fritschy JM, Luscher B (1998) Postsynaptic clustering of major GABAA receptor subtypes requires the gamma 2 subunit and gephyrin. Nat Neurosci 1(7):563–571. doi: 10.1038/2798 CrossRefPubMedGoogle Scholar
  20. Eyre MD, Renzi M, Farrant M, Nusser Z (2012) Setting the time course of inhibitory synaptic currents by mixing multiple GABA(A) receptor alpha subunit isoforms. J Neurosci 32(17):5853–5867. doi: 10.1523/JNEUROSCI.6495-11.2012 PubMedCentralCrossRefPubMedGoogle Scholar
  21. Fan KY, Baufreton J, Surmeier DJ, Chan CS, Bevan MD (2012) Proliferation of external globus pallidus-subthalamic nucleus synapses following degeneration of midbrain dopamine neurons. J Neurosci 32(40):13718–13728. doi: 10.1523/JNEUROSCI.5750-11.2012 PubMedCentralCrossRefPubMedGoogle Scholar
  22. Farrant M, Nusser Z (2005) Variations on an inhibitory theme: phasic and tonic activation of GABA(A) receptors. Nat Rev Neurosci 6(3):215–229. doi: 10.1038/nrn1625 CrossRefPubMedGoogle Scholar
  23. Fritschy JM, Mohler H (1995) GABAA-receptor heterogeneity in the adult rat brain: differential regional and cellular distribution of seven major subunits. J Comp Neurol 359(1):154–194. doi: 10.1002/cne.903590111 CrossRefPubMedGoogle Scholar
  24. Fritschy J-M, Weinmann Oliver, Wenzel Andreas, Benke Dietmar (1998) Synapse-specific localisation of NMDA and GABAA receptor subunits revealed by antigen retrieval immunohistochemistry. J Comp Neurol 390:194–210CrossRefPubMedGoogle Scholar
  25. Fu W, Le Maitre E, Fabre V, Bernard JF, David Xu ZQ, Hokfelt T (2010) Chemical neuroanatomy of the dorsal raphe nucleus and adjacent structures of the mouse brain. J Comp Neurol 518(17):3464–3494. doi: 10.1002/cne.22407 CrossRefPubMedGoogle Scholar
  26. Gao B, Fritschy JM, Benke D, Mohler H (1993) Neuron-specific expression of GABAA-Receptor subtypes: differential association of the alpha1 and alpha3 subunits with serotinergic and GABAergic neurons. Neuroscience 54(4):881–892CrossRefPubMedGoogle Scholar
  27. Gervasoni D, Peyron C, Rampon C, Barbagli B, Chouvet G, Urbain N, Fort P, Luppi PH (2000) Role and origin of the GABAergic innervation of dorsal raphe serotonergic neurons. J Neurosci 20(11):4217–4225. Pii: 20/11/4217PubMedGoogle Scholar
  28. Gunn BG, Cunningham L, Cooper MA, Corteen NL, Seifi M, Swinny JD, Lambert JJ, Belelli D (2013) Dysfunctional astrocytic and synaptic regulation of hypothalamic glutamatergic transmission in a mouse model of early-life adversity: relevance to neurosteroids and programming of the stress response. J Neurosci 33(50):19534–19554. doi: 10.1523/JNEUROSCI.1337-13.2013 PubMedCentralCrossRefPubMedGoogle Scholar
  29. Hauger RL, Risbrough V, Oakley RH, Olivares-Reyes JA, Dautzenberg FM (2009) Role of CRF Receptor signaling in stress vulnerability, anxiety, and depression. Ann N Y Acad Sci 1179(1):120–143. doi: 10.1111/j.1749-6632.2009.05011.x PubMedCentralCrossRefPubMedGoogle Scholar
  30. Hortnagl H, Tasan RO, Wieselthaler A, Kirchmair E, Sieghart W, Sperk G (2013) Patterns of mRNA and protein expression for 12 GABAA receptor subunits in the mouse brain. Neuroscience 236:345–372. doi: 10.1016/j.neuroscience.2013.01.008 PubMedCentralCrossRefPubMedGoogle Scholar
  31. Jacobs BL, Azmitia EC (1992) Structure and function of the brain serotonin system. Physiol Rev 72(1):165–229PubMedGoogle Scholar
  32. Kennedy PJ, Feng J, Robison A, Maze I, Badimon A, Mouzon E, Chaudhury D, Damez-Werno DM, Haggarty SJ, Han M-H (2013) Class I HDAC inhibition blocks cocaine-induced plasticity by targeted changes in histone methylation. Nat Neurosci 16(4):434–440PubMedCentralCrossRefPubMedGoogle Scholar
  33. Keshavarzy F, Bonnet C, Bezhadi G, Cespuglio R (2014) Expression patterns of c-Fos early gene and phosphorylated ERK in the rat brain following 1-h immobilization stress: concomitant changes induced in association with stress-related sleep rebound. Brain Struct Funct. doi: 10.1007/s00429-014-0728-6 PubMedGoogle Scholar
  34. Kirby LG, Allen AR, Lucki I (1995) Regional differences in the effects of forced swimming on extracellular levels of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid. Brain Res 682(1–2):189–196. doi: 10.1016/0006-8993(95)00349-U CrossRefPubMedGoogle Scholar
  35. Kirby LG, Chou-Green JM, Davis K, Lucki I (1997) The effects of different stressors on extracellular 5-hydroxytryptamine and 5-hydroxyindoleacetic acid. Brain Res 760(1–2):218–230. doi: 10.1016/S0006-8993(97)00287-4 CrossRefPubMedGoogle Scholar
  36. Kirby LG, Rice KC, Valentino RJ (2000) Effects of corticotropin-releasing factor on neuronal activity in the serotonergic dorsal raphe nucleus. Neuropsychopharmacology 22(2):148–162. doi: 10.1016/S0893-133X(99)00093-7 CrossRefPubMedGoogle Scholar
  37. Kirby LG, Freeman-Daniels E, Lemos JC, Nunan JD, Lamy C, Akanwa A, Beck SG (2008) Corticotropin-releasing factor increases GABA synaptic activity and induces inward current in 5-hydroxytryptamine dorsal raphe neurons. J Neurosci 28(48):12927–12937. doi: 10.1523/JNEUROSCI.2887-08.2008 PubMedCentralCrossRefPubMedGoogle Scholar
  38. Kittler JT, Delmas P, Jovanovic JN, Brown DA, Smart TG, Moss SJ (2000) Constitutive endocytosis of GABAA receptors by an association with the adaptin AP2 complex modulates inhibitory synaptic currents in hippocampal neurons. J Neurosci 20(21):7972–7977PubMedGoogle Scholar
  39. Kittler JT, Chen G, Honing S, Bogdanov Y, McAinsh K, Arancibia-Carcamo IL, Jovanovic JN, Pangalos MN, Haucke V, Yan Z (2005) Phospho-dependent binding of the clathrin AP2 adaptor complex to GABAA receptors regulates the efficacy of inhibitory synaptic transmission. Proc Natl Acad Sci USA 102(41):14871–14876PubMedCentralCrossRefPubMedGoogle Scholar
  40. Koester C, Rudolph U, Haenggi T, Papilloud A, Fritschy JM, Crestani F (2013) Dissecting the role of diazepam-sensitive gamma-aminobutyric acid type A receptors in defensive behavioral reactivity to mild threat. Pharmacol Biochem Behav 103(3):541–549. doi: 10.1016/j.pbb.2012.10.004 CrossRefPubMedGoogle Scholar
  41. Kos CH (2004) Cre/loxP system for generating tissue-specific knockout mouse models. Nutr Rev 62(6 Pt 1):243–246PubMedGoogle Scholar
  42. Kralic JE, Sidler C, Parpan F, Homanics GE, Morrow AL, Fritschy JM (2006) Compensatory alteration of inhibitory synaptic circuits in cerebellum and thalamus of gamma-aminobutyric acid type A receptor alpha1 subunit knockout mice. J Comp Neurol 495(4):408–421. doi: 10.1002/cne.20866 CrossRefPubMedGoogle Scholar
  43. Lamy CM, Beck SG (2010) Swim stress differentially blocks CRF receptor mediated responses in dorsal raphe nucleus. Psychoneuroendocrinology 35(9):1321–1332PubMedCentralCrossRefPubMedGoogle Scholar
  44. Lee HS, Kim MA, Valentino RJ, Waterhouse BD (2003) Glutamatergic afferent projections to the dorsal raphe nucleus of the rat. Brain Res 963(1–2):57–71PubMedGoogle Scholar
  45. Lemos JC, Zhang G, Walsh T, Kirby LG, Akanwa A, Brooks-Kayal A, Beck SG (2011) Stress-hyperresponsive WKY rats demonstrate depressed dorsal raphe neuronal excitability and dysregulated CRF-mediated responses. Neuropsychopharmacology 36(4):721–734. doi: 10.1038/npp.2010.200 PubMedCentralCrossRefPubMedGoogle Scholar
  46. Lorenzo L-E, Russier M, Barbe A, Fritschy J-M, Bras H (2007) Differential organization of γ-aminobutyric acid type A and glycine receptors in the somatic and dendritic compartments of rat abducens motoneurons. J Comp Neurol 504(2):112–126. doi: 10.1002/cne.21442 CrossRefPubMedGoogle Scholar
  47. Lorincz A, Nusser Z (2008) Cell-type-dependent molecular composition of the axon initial segment. J Neurosci 28(53):14329–14340. doi: 10.1523/JNEUROSCI.4833-08.2008 PubMedCentralCrossRefPubMedGoogle Scholar
  48. Low K, Crestani F, Keist R, Benke D, Brunig I, Benson JA, Fritschy JM, Rulicke T, Bluethmann H, Mohler H, Rudolph U (2000) Molecular and neuronal substrate for the selective attenuation of anxiety. Science 290(5489):131–134CrossRefPubMedGoogle Scholar
  49. Luscher B, Fuchs T, Kilpatrick Casey L (2011) GABAA Receptor trafficking-mediated plasticity of inhibitory synapses. Neuron 70(3):385–409. doi: 10.1016/j.neuron.2011.03.024 PubMedCentralCrossRefPubMedGoogle Scholar
  50. Maguire EP, Mitchell EA, Greig SJ, Corteen N, Balfour DJ, Swinny JD, Lambert JJ, Belelli D (2013) Extrasynaptic glycine receptors of rodent dorsal raphe serotonergic neurons: a sensitive target for ethanol. Neuropsychopharmacology. doi: 10.1038/npp.2013.326 PubMedGoogle Scholar
  51. Marowsky A, Rudolph U, Fritschy JM, Arand M (2012) Tonic inhibition in principal cells of the amygdala: a central role for alpha3 subunit-containing GABAA receptors. J Neurosci 32(25):8611–8619. doi: 10.1523/JNEUROSCI.4404-11.2012 CrossRefPubMedGoogle Scholar
  52. O’Hearn E, Molliver ME (1984) Organization of raphe-cortical projections in rat: a quantitative retrograde study. Brain Res Bull 13(6):709–726CrossRefPubMedGoogle Scholar
  53. Olsen RW, Sieghart W (2009) GABAA receptors: subtypes provide diversity of function and pharmacology. Neuropharmacology 56(1):141–148. doi: 10.1016/j.neuropharm.2008.07.045 PubMedCentralCrossRefPubMedGoogle Scholar
  54. Orchinik M, Weiland NG, McEwen BS (1995) Chronic exposure to stress levels of corticosterone alters GABAA receptor subunit mRNA levels in rat hippocampus. Mol Brain Res 34(1):29–37. doi: 10.1016/0169-328X(95)00118-C CrossRefPubMedGoogle Scholar
  55. Paxinos G, Franklin KBJ (2004) The mouse brain in stereotaxic coordinates. Compact 2nd edn. Elsevier Academic Press, Amsterdam; BostonGoogle Scholar
  56. Peng Z, Hauer B, Mihalek RM, Homanics GE, Sieghart W, Olsen RW, Houser CR (2002) GABAA receptor changes in δ subunit-deficient mice: altered expression of α4 and γ2 subunits in the forebrain. J Comp Neurol 446(2):179–197. doi: 10.1002/cne.10210 CrossRefPubMedGoogle Scholar
  57. Petrov T, Krukoff TL, Jhamandas JH (1994) Chemically defined collateral projections from the pons to the central nucleus of the amygdala and hypothalamic paraventricular nucleus in the rat. Cell Tissue Res 277(2):289–295CrossRefPubMedGoogle Scholar
  58. Pfeiffer F, Simler R, Grenningloh G, Betz H (1984) Monoclonal antibodies and peptide mapping reveal structural similarities between the subunits of the glycine receptor of rat spinal cord. Proc Natl Acad Sci USA 81(22):7224–7227PubMedCentralCrossRefPubMedGoogle Scholar
  59. Pirker S, Schwarzer C, Wieselthaler A, Sieghart W, Sperk G (2000) GABA(A) receptors: immunocytochemical distribution of 13 subunits in the adult rat brain. Neuroscience 101(4):815–850. Pii: S0306-4522(00)00442-5CrossRefPubMedGoogle Scholar
  60. Poltl A, Hauer B, Fuchs K, Tretter V, Sieghart W (2003) Subunit composition and quantitative importance of GABA(A) receptor subtypes in the cerebellum of mouse and rat. J Neurochem 87(6):1444–1455. Pii: 2315CrossRefPubMedGoogle Scholar
  61. Poulopoulos A, Aramuni G, Meyer G, Soykan T, Hoon M, Papadopoulos T, Zhang M, Paarmann I, Fuchs C, Harvey K, Jedlicka P, Schwarzacher SW, Betz H, Harvey RJ, Brose N, Zhang W, Varoqueaux F (2009) Neuroligin 2 drives postsynaptic assembly at perisomatic inhibitory synapses through gephyrin and collybistin. Neuron 63(5):628–642. doi: 10.1016/j.neuron.2009.08.023 CrossRefPubMedGoogle Scholar
  62. Price ML, Lucki I (2001) Regulation of serotonin release in the lateral septum and striatum by corticotropin-releasing factor. J Neurosci 21(8):2833–2841PubMedGoogle Scholar
  63. Price ML, Curtis AL, Kirby LG, Valentino RJ, Lucki I (1998) Effects of corticotropin-releasing factor on brain serotonergic activity. Neuropsychopharmacology 18(6):492–502. doi: 10.1016/S0893-133X(97)00197-8 CrossRefPubMedGoogle Scholar
  64. Renthal W, Maze I, Krishnan V, Covington HE 3rd, Xiao G, Kumar A, Russo SJ, Graham A, Tsankova N, Kippin TE, Kerstetter KA, Neve RL, Haggarty SJ, McKinsey TA, Bassel-Duby R, Olson EN, Nestler EJ (2007) Histone deacetylase 5 epigenetically controls behavioral adaptations to chronic emotional stimuli. Neuron 56(3):517–529. doi: 10.1016/j.neuron.2007.09.032 CrossRefPubMedGoogle Scholar
  65. Roche M, Commons KG, Peoples A, Valentino RJ (2003) Circuitry underlying regulation of the serotonergic system by swim stress. J Neurosci 23(3):970–977. Pii: 23/3/970PubMedGoogle Scholar
  66. Rudolph U, Knoflach F (2011) Beyond classical benzodiazepines: novel therapeutic potential of GABAA receptor subtypes. Nat Rev Drug Discov 10(9):685–697. doi: 10.1038/nrd3502nrd3502 PubMedCentralCrossRefPubMedGoogle Scholar
  67. Schneider Gasser EM, Duveau V, Prenosil GA, Fritschy JM (2007) Reorganization of GABAergic circuits maintains GABAA receptor-mediated transmission onto CA1 interneurons in alpha1-subunit-null mice. Eur J Neurosci 25(11):3287–3304. doi: 10.1111/j.1460-9568.2007.05558.x CrossRefPubMedGoogle Scholar
  68. Seifi M, Corteen NL, van der Want JJ, Metzger F, Swinny JD (2014) Localization of NG2 immunoreactive neuroglia cells in the rat locus coeruleus and their plasticity in response to stress. Front Neuroanat 8:31. doi: 10.3389/fnana.2014.00031 PubMedCentralPubMedGoogle Scholar
  69. Shikanai H, Yoshida T, Konno K, Yamasaki M, Izumi T, Ohmura Y, Watanabe M, Yoshioka M (2012) Distinct neurochemical and functional properties of GAD67-containing 5-HT neurons in the rat dorsal raphe nucleus. J Neurosci 32(41):14415–14426. doi: 10.1523/JNEUROSCI.5929-11.2012 CrossRefPubMedGoogle Scholar
  70. Shoji H, Mizoguchi K (2010) Acute and repeated stress differentially regulates behavioral, endocrine, neural parameters relevant to emotional and stress response in young and aged rats. Behav Brain Res 211(2):169–177. doi: 10.1016/j.bbr.2010.03.025 CrossRefPubMedGoogle Scholar
  71. Smith KS, Engin E, Meloni EG, Rudolph U (2012) Benzodiazepine-induced anxiolysis and reduction of conditioned fear are mediated by distinct GABAA receptor subtypes in mice. Neuropharmacology 63(2):250–258. doi: 10.1016/j.neuropharm.2012.03.001 PubMedCentralCrossRefPubMedGoogle Scholar
  72. Soiza-Reilly M, Anderson WB, Vaughan CW, Commons KG (2013) Presynaptic gating of excitation in the dorsal raphe nucleus by GABA. Proc Natl Acad Sci USA 110(39):15800–15805. doi: 10.1073/pnas.1304505110 PubMedCentralCrossRefPubMedGoogle Scholar
  73. Studer R, von Boehmer L, Haenggi T, Schweizer C, Benke D, Rudolph U, Fritschy JM (2006) Alteration of GABAergic synapses and gephyrin clusters in the thalamic reticular nucleus of GABAA receptor alpha3 subunit-null mice. Eur J Neurosci 24(5):1307–1315. doi: 10.1111/j.1460-9568.2006.05006.x CrossRefPubMedGoogle Scholar
  74. Sur C, Wafford KA, Reynolds DS, Hadingham KL, Bromidge F, Macaulay A, Collinson N, O’Meara G, Howell O, Newman R, Myers J, Atack JR, Dawson GR, McKernan RM, Whiting PJ, Rosahl TW (2001) Loss of the major GABA(A) receptor subtype in the brain is not lethal in mice. J Neurosci 21(10):3409–3418 PubMedGoogle Scholar
  75. Tamamaki N, Yanagawa Y, Tomioka R, Miyazaki J-I, Obata K, Kaneko T (2003) Green fluorescent protein expression and colocalization with calretinin, parvalbumin, and somatostatin in the GAD67-GFP knock-in mouse. J Comp Neurol 467(1):60–79. doi: 10.1002/cne.10905 CrossRefPubMedGoogle Scholar
  76. Tretter V, Kerschner B, Milenkovic I, Ramsden SL, Ramerstorfer J, Saiepour L, Maric H-M, Moss SJ, Schindelin H, Harvey RJ, Sieghart W, Harvey K (2011) Molecular basis of the γ-aminobutyric acid A receptor α3 subunit interaction with the clustering protein gephyrin. J Biol Chem 286(43):37702–37711. doi: 10.1074/jbc.M111.291336 PubMedCentralCrossRefPubMedGoogle Scholar
  77. Tsankova N, Renthal W, Kumar A, Nestler EJ (2007) Epigenetic regulation in psychiatric disorders. Nat Rev Neurosci 8(5):355–367. doi: 10.1038/nrn2132 CrossRefPubMedGoogle Scholar
  78. Uchida S, Hara K, Kobayashi A, Otsuki K, Yamagata H, Hobara T, Suzuki T, Miyata N, Watanabe Y (2011) Epigenetic status of Gdnf in the ventral striatum determines susceptibility and adaptation to daily stressful events. Neuron 69(2):359–372. doi: 10.1016/j.neuron.2010.12.023 CrossRefPubMedGoogle Scholar
  79. Valentino RJ, Liouterman L, Van Bockstaele EJ (2001) Evidence for regional heterogeneity in corticotropin-releasing factor interactions in the dorsal raphe nucleus. J Comp Neurol 435(4):450–463. doi: 10.1002/cne.1043 CrossRefPubMedGoogle Scholar
  80. Varoqueaux F, Jamain S, Brose N (2004) Neuroligin 2 is exclusively localized to inhibitory synapses. Eur J Cell Biol 83(9):449–456. doi: 10.1078/0171-9335-00410 CrossRefPubMedGoogle Scholar
  81. Vertes RP (1991) A PHA-L analysis of ascending projections of the dorsal raphe nucleus in the rat. J Comp Neurol 313(4):643–668. doi: 10.1002/cne.903130409 CrossRefPubMedGoogle Scholar
  82. Vithlani M, Hines RM, Zhong P, Terunuma M, Hines DJ, Revilla-Sanchez R, Jurd R, Haydon P, Rios M, Brandon N, Yan Z, Moss SJ (2013) The ability of BDNF to modify neurogenesis and depressive-like behaviors is dependent upon phosphorylation of tyrosine residues 365/367 in the GABA(A)-receptor gamma2 subunit. J Neurosci 33(39):15567–15577. doi: 10.1523/JNEUROSCI.1845-13.2013 PubMedCentralCrossRefPubMedGoogle Scholar
  83. Waselus M, Valentino RJ, Van Bockstaele EJ (2005) Ultrastructural evidence for a role of γ-aminobutyric acid in mediating the effects of corticotropin-releasing factor on the rat dorsal raphe serotonin system. J Comp Neurol 482(2):155–165CrossRefPubMedGoogle Scholar
  84. Waselus M, Valentino RJ, Van Bockstaele EJ (2011) Collateralized dorsal raphe nucleus projections: a mechanism for the integration of diverse functions during stress. J Chem Neuroanat 41(4):266–280. doi: 10.1016/j.jchemneu.2011.05.011 PubMedCentralCrossRefPubMedGoogle Scholar
  85. Watanabe M, Fukaya M, Sakimura K, Manabe T, Mishina M, Inoue Y (1998) Selective scarcity of NMDA receptor channel subunits in the stratum lucidum (mossy fibre-recipient layer) of the mouse hippocampal CA3 subfield. Eur J Neurosci 10(2):478–487CrossRefPubMedGoogle Scholar
  86. Weaver ICG, Meaney MJ, Szyf M (2006) Maternal care effects on the hippocampal transcriptome and anxiety-mediated behaviors in the offspring that are reversible in adulthood. Proc Natl Acad Sci USA 103(9):3480–3485. doi: 10.1073/pnas.0507526103 PubMedCentralCrossRefPubMedGoogle Scholar
  87. Wieland HA, Luddens H, Seeburg PH (1992) A single histidine in GABAA receptors is essential for benzodiazepine agonist binding. J Biol Chem 267(3):1426–1429PubMedGoogle Scholar
  88. Wisden W (2010) Cre-ating ways to serotonin. Front Neurosci 4:167. doi: 10.3389/fnins.2010.00167 PubMedCentralCrossRefPubMedGoogle Scholar
  89. Wisden W, Laurie DJ, Monyer H, Seeburg PH (1992) The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. I. Telencephalon, diencephalon, mesencephalon. J Neurosci 12(3):1040–1062PubMedGoogle Scholar
  90. Wood SK, Zhang X-Y, Reyes BAS, Lee CS, Van Bockstaele EJ, Valentino RJ (2013) Cellular adaptations of dorsal raphe serotonin neurons associated with the development of active coping in response to social stress. Biol Psychiatry 73(11):1087–1094PubMedCentralCrossRefPubMedGoogle Scholar
  91. Xu ZQ, Hokfelt T (1997) Expression of galanin and nitric oxide synthase in subpopulations of serotonin neurons of the rat dorsal raphe nucleus. J Chem Neuroanat 13(3):169–187CrossRefPubMedGoogle Scholar
  92. Yee BK, Keist R, von Boehmer L, Studer R, Benke D, Hagenbuch N, Dong Y, Malenka RC, Fritschy JM, Bluethmann H, Feldon J, Mohler H, Rudolph U (2005) A schizophrenia-related sensorimotor deficit links alpha 3-containing GABAA receptors to a dopamine hyperfunction. Proc Natl Acad Sci USA 102(47):17154–17159. doi: 10.1073/pnas.0508752102 PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Nicole L. Corteen
    • 1
  • Jessica A. Carter
    • 1
  • Uwe Rudolph
    • 2
  • Delia Belelli
    • 3
  • Jeremy J. Lambert
    • 3
  • Jerome D. Swinny
    • 1
    Email author
  1. 1.Institute for Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical SciencesUniversity of PortsmouthPortsmouthUK
  2. 2.Laboratory of Genetic Neuropharmacology, McLean Hospital and Department of PsychiatryHarvard Medical SchoolBelmontUSA
  3. 3.Division of Neuroscience, Medical Research InstituteNinewells Hospital and Medical School, Ninewells Hospital, Dundee UniversityDundeeUK

Personalised recommendations