Advertisement

Experimental Brain Research

, Volume 236, Issue 4, pp 919–931 | Cite as

Hippocampal area CA2: an emerging modulatory gateway in the hippocampal circuit

  • Amrita Benoy
  • Ananya Dasgupta
  • Sreedharan Sajikumar
Review

Abstract

The hippocampus is a critical brain region for the formation of declarative memories. While social memory had long been attributed to be a function of the hippocampus, it is only of late that the area CA2 of the hippocampus was demarcated as essential for social memory formation. In addition to this distinct role, CA2 possesses unique molecular, structural and physiological characteristics compared to the other CA regions—CA1 and CA3, and the dentate gyrus (DG). CA2 pyramidal neurons are positioned at a location between CA1 and CA3, receiving inputs from CA3 and DG, in addition to forming a powerful disynaptic circuit with direct input from the entorhinal cortical layer II neurons. CA2 also receives direct inputs from the hypothalamic regions and displays a unique expression pattern for receptors for neuromodulators. The location, inputs, and molecular signatures of the area CA2 point to the possibility that CA2 serves as a modulatory gateway that processes information from the entorhinal cortex and CA3, before relaying them onto CA1, the major output of the hippocampus. This review discusses recent findings regarding plasticity and neuromodulation in the CA2 region of the hippocampus, and how this may have the potential to influence plasticity in connecting circuits, and thereby memory and behaviour.

Keywords

Long-term potentiation CA2 region Substance P Synaptic tagging Synaptic tagging/capture Social memory Neuromodulators 

Notes

Acknowledgements

This work was supported by the National Medical Research Council (NMRC) Grants NMRC-CBRG-0099-2015, NMRC-OFIRG-0037-2017 and National University of Singapore (NUS) University Strategic Research Grants. A.B and A.D were supported by NUS Research Scholarship.

References

  1. Albeck D, Bullock N, Marrs K et al (1993) Antidromic activation of a peptidergic pathway in the limbic system of the male rat. Brain Res 606:171–174CrossRefPubMedGoogle Scholar
  2. Andersen P (2007) The hippocampus bookGoogle Scholar
  3. Andersen P, Bliss TVP, Skrede KK (1971) Lamellar organization of hippocampal excitatory pathways. Exp Brain Res 13:222–238.  https://doi.org/10.1007/BF00234087 PubMedGoogle Scholar
  4. Arai A, Lynch G (1992) Factors regulating the magnitude of long-term potentiation induced by theta pattern stimulation. Brain Res 598:173–184CrossRefPubMedGoogle Scholar
  5. Bale TL, Davis AM, Auger AP et al (2001) CNS region-specific oxytocin receptor expression: importance in regulation of anxiety and sex behavior. J Neurosci 21:2546–2552PubMedGoogle Scholar
  6. Barco A, Lopez de Armentia M, Alarcon JM (2008) Synapse-specific stabilization of plasticity processes: the synaptic tagging and capture hypothesis revisited 10 years later. Neurosci Biobehav Rev 32:831–851.  https://doi.org/10.1016/j.neubiorev.2008.01.002 CrossRefPubMedGoogle Scholar
  7. Benes FM, Sorensen I, Bird ED (1991) Reduced neuronal size in posterior hippocampus of schizophrenic patients. Schizophr Bull 17:597–608CrossRefPubMedGoogle Scholar
  8. Benes FM, Kwok EW, Vincent SL, Todtenkopf MS (1998) A reduction of nonpyramidal cells in sector CA2 of schizophrenics and manic depressives. Biol Psychiatry 44:88–97CrossRefPubMedGoogle Scholar
  9. Bielsky IF, Hu S-B, Szegda KL et al (2004) Profound impairment in social recognition and reduction in anxiety-like behavior in vasopressin V1a receptor knockout mice. Neuropsychopharmacology 29:483–493.  https://doi.org/10.1038/sj.npp.1300360 CrossRefPubMedGoogle Scholar
  10. Bielsky IF, Hu S-B, Ren X et al (2005) The V1a vasopressin receptor is necessary and sufficient for normal social recognition: a gene replacement study. Neuron 47:503–513.  https://doi.org/10.1016/j.neuron.2005.06.031 CrossRefPubMedGoogle Scholar
  11. Bird CM, Burgess N (2008) The hippocampus and memory: insights from spatial processing. Nat Rev Neurosci 9:182–194.  https://doi.org/10.1038/nrn2335 CrossRefPubMedGoogle Scholar
  12. Bliss TV, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39.  https://doi.org/10.1038/361031a0 CrossRefPubMedGoogle Scholar
  13. Bliss TVP, Lomo T (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the preforant path. J Physiol 232:331–356 (4727084) CrossRefPubMedPubMedCentralGoogle Scholar
  14. Borhegyi Z, Leranth C (1997) Substance P innervation of the rat hippocampal formation. J Comp Neurol 384:41–58CrossRefPubMedGoogle Scholar
  15. Brückner G, Brauer K, Härtig W et al (1993) Perineuronal nets provide a polyanionic, glia-associated form of microenvironment around certain neurons in many parts of the rat brain. Glia 8:183–200.  https://doi.org/10.1002/glia.440080306 CrossRefPubMedGoogle Scholar
  16. Brun VH, Otnass MK, Molden S et al (2002) Place cells and place recognition maintained by direct entorhinal-hippocampal circuitry. Science 296:2243–2246.  https://doi.org/10.1126/science.1071089 CrossRefPubMedGoogle Scholar
  17. Caffé AR, van Leeuwen FW, Luiten PGM (1987) Vasopressin cells in the medial amygdala of the rat project to the lateral septum and ventral hippocampus. J Comp Neurol 261:237–252.  https://doi.org/10.1002/cne.902610206 CrossRefPubMedGoogle Scholar
  18. Carstens KE, Phillips ML, Pozzo-Miller L et al (2016) Perineuronal nets suppress plasticity of excitatory synapses on CA2 pyramidal neurons. J Neurosci 36:6312–6320.  https://doi.org/10.1523/JNEUROSCI.0245-16.2016 CrossRefPubMedPubMedCentralGoogle Scholar
  19. Carter CS (1998) Neuroendocrine perspectives on social attachment and love. Psychoneuroendocrinology 23:779–818CrossRefPubMedGoogle Scholar
  20. Carter CS, Altemus M (1997) Integrative functions of lactational hormones in social behavior and stress management. Ann N Y Acad Sci 807:164–174.  https://doi.org/10.1111/j.1749-6632.1997.tb51918.x CrossRefPubMedGoogle Scholar
  21. Carter CS, Altemus M, Chrousos GP (2001) Neuroendocrine and emotional changes in the post-partum period. Prog Brain Res 133:241–249CrossRefPubMedGoogle Scholar
  22. Chevaleyre V, Piskorowski RA (2016) Hippocampal area CA2: an overlooked but promising therapeutic target. Trends Mol MedGoogle Scholar
  23. Chevaleyre V, Siegelbaum SA (2010) Strong CA2 pyramidal neuron synapses define a powerful disynaptic cortico-hippocampal loop. Neuron 66:560–572.  https://doi.org/10.1016/j.neuron.2010.04.013 CrossRefPubMedPubMedCentralGoogle Scholar
  24. Coccaro EF, Kavoussi RJ, Hauger RL et al (1998) Cerebrospinal fluid vasopressin levels: correlates with aggression and serotonin function in personality-disordered subjects. Arch Gen Psychiatry 55:708–714.  https://doi.org/10.1001/archpsyc.55.8.708 CrossRefPubMedGoogle Scholar
  25. Cui Z, Gerfen CR, Young WS (2013) Hypothalamic and other connections with dorsal CA2 area of the mouse hippocampus. J Comp Neurol 521:1844–1866.  https://doi.org/10.1002/cne.23263 CrossRefPubMedPubMedCentralGoogle Scholar
  26. Dale E, Pehrson AL, Jeyarajah T et al (2016) Effects of serotonin in the hippocampus: how SSRIs and multimodal antidepressants might regulate pyramidal cell function. CNS Spectr 21:143–161.  https://doi.org/10.1017/S1092852915000425 CrossRefPubMedGoogle Scholar
  27. Dantzer R (1999) Vasopressin, gonadal steroids and social recognition. Adv Brain Vasopressin 409–414Google Scholar
  28. Dasgupta A, Baby N, Krishna K et al (2017) Substance P induces plasticity and synaptic tagging/capture in rat hippocampal area CA2. Proc Natl Acad Sci 201711267.  https://doi.org/10.1073/PNAS.1711267114
  29. DeVito LM, Konigsberg R, Lykken C et al (2009) Vasopressin 1b receptor knock-out impairs memory for temporal order. J Neurosci 29:2676–2683.  https://doi.org/10.1523/JNEUROSCI.5488-08.2009 CrossRefPubMedPubMedCentralGoogle Scholar
  30. Dluzen DE, Muraoka S, Engelmann M, Landgraf R (1998) The effects of infusion of arginine vasopressin, oxytocin, or their antagonists into the olfactory bulb upon social recognition responses in male rats. Peptides 19:999–1005.  https://doi.org/10.1016/S0196-9781(98)00047-3 CrossRefPubMedGoogle Scholar
  31. Donaldson ZR, Young LJ (2008) Oxytocin, vasopressin, and the neurogenetics of socialityGoogle Scholar
  32. Dudek SM, Bear MF (1992) Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-methyl-d-aspartate receptor blockade. Proc Natl Acad Sci 89:4363–4367.  https://doi.org/10.1073/pnas.89.10.4363 CrossRefPubMedPubMedCentralGoogle Scholar
  33. Dudek SM, Alexander GM, Farris S (2016) Rediscovering area CA2: unique properties and functions. Nat Rev Neurosci 17:89–102.  https://doi.org/10.1038/nrn.2015.22 CrossRefPubMedPubMedCentralGoogle Scholar
  34. Dunnett SB (2005) Dopamine. ElsevierGoogle Scholar
  35. Dunwiddie TV, Masino SA (2001) The role and regulation of adenosine in the central nervous system. Annu Rev Neurosci 24:31–55.  https://doi.org/10.1146/annurev.neuro.24.1.31 CrossRefPubMedGoogle Scholar
  36. Englemann M, Wotjak CT, Ebner K, Landgraf R (2000) Behavioural impact of intraseptally released vasopressin and oxytocin in rats. Exp Physiol 85:125s–130 s.  https://doi.org/10.1111/j.1469-445X.2000.tb00015.x CrossRefGoogle Scholar
  37. Everts HG, Koolhaas J (1999) Differential modulation of lateral septal vasopressin receptor blockade in spatial learning, social recognition, and anxiety-related behaviors in rats. Behav Brain Res 99:7–16.  https://doi.org/10.1016/S0166-4328(98)00004-7 CrossRefPubMedGoogle Scholar
  38. Felix-Ortiz AC, Tye KM (2014) Amygdala inputs to the ventral hippocampus bidirectionally modulate social behavior. J Neurosci 34:586–595.  https://doi.org/10.1523/JNEUROSCI.4257-13.2014 CrossRefPubMedPubMedCentralGoogle Scholar
  39. Ferguson JN, Aldag JM, Insel TR, Young LJ (2001) Oxytocin in the medial amygdala is essential for social recognition in the mouse. J Neurosci 21:8278–8285PubMedGoogle Scholar
  40. Ferris CF, Potegal M (1988) Vasopressin receptor blockade in the anterior hypothalamus suppresses aggression in hamsters. Physiol Behav 44:235–239.  https://doi.org/10.1016/0031-9384(88)90144-8 CrossRefPubMedGoogle Scholar
  41. Frey U, Morris RG (1997) Synaptic tagging and long-term potentiation. Nature 385:533–536.  https://doi.org/10.1038/385533a0 CrossRefPubMedGoogle Scholar
  42. Frey U, Morris RG (1998a) Synaptic tagging: implications for late maintenance of hippocampal long-term potentiation. Trends Neurosci 21:181–188CrossRefPubMedGoogle Scholar
  43. Frey U, Morris RG (1998b) Weak before strong: dissociating synaptic tagging and plasticity-factor accounts of late-LTP. Neuropharmacology 37:545–552CrossRefPubMedGoogle Scholar
  44. Frischknecht R, Heine M, Perrais D et al (2009) Brain extracellular matrix affects AMPA receptor lateral mobility and short-term synaptic plasticity. Nat Neurosci 12:897–904.  https://doi.org/10.1038/nn.2338 CrossRefPubMedGoogle Scholar
  45. Golding NL, Mickus TJ, Katz Y et al (2005) Factors mediating powerful voltage attenuation along CA1 pyramidal neuron dendrites. J Physiol 568:69–82.  https://doi.org/10.1113/jphysiol.2005.086793 CrossRefPubMedPubMedCentralGoogle Scholar
  46. Hargreaves EL, Rao G, Lee I, Knierim JJ (2005) Major dissociation between medial and lateral entorhinal input to dorsal hippocampus. Science 308:1792–1794.  https://doi.org/10.1126/science.1110449 CrossRefPubMedGoogle Scholar
  47. Heinrichs M, von Dawans B, Domes G (2009) Oxytocin, vasopressin, and human social behavior. Front Neuroendocrinol 30:548–557.  https://doi.org/10.1016/j.yfrne.2009.05.005 CrossRefPubMedGoogle Scholar
  48. Hensler J (2006) Serotonergic modulation of the limbic systemGoogle Scholar
  49. Hitti FL, Siegelbaum SA (2014) The hippocampal CA2 region is essential for social memory. Nature 508:88–92.  https://doi.org/10.1038/nature13028 CrossRefPubMedPubMedCentralGoogle Scholar
  50. Huston JP, Haas HL, Boix F et al (1996) Extracellular adenosine levels in neostriatum and hippocampus during rest and activity periods of rats. Neuroscience 73:99–107CrossRefPubMedGoogle Scholar
  51. Insel TR, Young LJ (2001) The neurobiology of attachment. Nat Rev Neurosci 2:129–136.  https://doi.org/10.1038/35053579 CrossRefPubMedGoogle Scholar
  52. Insel TR, Wang ZX, Ferris CF (1994) Patterns of brain vasopressin receptor distribution associated with social organization in microtine rodents. J Neurosci 14:5381–5392CrossRefPubMedGoogle Scholar
  53. Ito M, Shirao T, Doya K, Sekino Y (2009) Three-dimensional distribution of Fos-positive neurons in the supramammillary nucleus of the rat exposed to novel environment. Neurosci Res 64:397–402.  https://doi.org/10.1016/j.neures.2009.04.013 CrossRefPubMedGoogle Scholar
  54. Khan ZU, Gutiérrez A, Martín R et al (2000) Dopamine D5 receptors of rat and human brain. Neuroscience 100:689–699CrossRefPubMedGoogle Scholar
  55. Kirk IJ, McNaughton N (1991) Supramammillary cell firing and hippocampal rhythmical slow activity. Neuroreport 2:723.  https://doi.org/10.1097/00001756-199111000-00023 CrossRefPubMedGoogle Scholar
  56. Kirk IJ, McNaughton N (1993) Mapping the differential effects of procaine on frequency and amplitude of reticularly elicited hippocampal rhythmical slow activity. Hippocampus 3:517–525.  https://doi.org/10.1002/hipo.450030411 CrossRefPubMedGoogle Scholar
  57. Knable MB, Barci BM, Webster MJ et al (2004) Molecular abnormalities of the hippocampus in severe psychiatric illness: postmortem findings from the Stanley Neuropathology Consortium. Mol Psychiatry 9:609–620.  https://doi.org/10.1038/sj.mp.4001471 CrossRefPubMedGoogle Scholar
  58. Kocsis B, Vertes RP (1994) Characterization of neurons of the supramammillary nucleus and mammillary body that discharge rhythmically with the hippocampal theta rhythm in the rat. J Neurosci 14:7040–7052CrossRefPubMedGoogle Scholar
  59. Kohara K, Pignatelli M, Rivest AJ et al (2013) Cell type-specific genetic and optogenetic tools reveal hippocampal CA2 circuits. Nat Neurosci 17:269–279.  https://doi.org/10.1038/nn.3614 CrossRefPubMedPubMedCentralGoogle Scholar
  60. Koolhaas JM, Van Den Brink THC, Roozendaal B, Boorsma F (1990) Medial amygdala and aggressive behavior: Interaction between testosterone and vasopressin. Aggress Behav 16:223–229. https://doi.org/10.1002/1098-2337(1990)16:3/4<223::AID-AB2480160308>3.0.CO;2-#Google Scholar
  61. Landgraf R, Gerstberger R, Montkowski A et al (1995) V1 vasopressin receptor antisense oligodeoxynucleotide into septum reduces vasopressin binding, social discrimination abilities, and anxiety-related behavior in rats. J Neurosci 15:4250–4258CrossRefPubMedGoogle Scholar
  62. Langosch JM, Kupferschmid S, Heinen M et al (2005) Effects of substance P and its antagonist L-733060 on long term potentiation in guinea pig hippocampal slices. Prog Neuro-Psychopharmacol Biol Psychiatry 29:315–319.  https://doi.org/10.1016/j.pnpbp.2004.11.017 CrossRefGoogle Scholar
  63. Lee SE, Simons SB, Heldt SA et al (2010) RGS14 is a natural suppressor of both synaptic plasticity in CA2 neurons and hippocampal-based learning and memory. Proc Natl Acad Sci 107:16994–16998.  https://doi.org/10.1073/pnas.1005362107 CrossRefPubMedPubMedCentralGoogle Scholar
  64. Lein ES, Callaway EM, Albright TD, Gage FH (2005) Redefining the boundaries of the hippocampal CA2 subfield in the mouse using gene expression and 3-dimensional reconstruction. J Comp Neurol 485:1–10.  https://doi.org/10.1002/cne.20426 CrossRefPubMedGoogle Scholar
  65. Lin Y-T, Chen C-C, Huang C-C et al (2017) Oxytocin stimulates hippocampal neurogenesis via oxytocin receptor expressed in CA3 pyramidal neurons. Nat Commun 8:537.  https://doi.org/10.1038/s41467-017-00675-5 CrossRefPubMedPubMedCentralGoogle Scholar
  66. McCarthy MM, McDonald CH, Brooks PJ, Goldman D (1996) An anxiolytic action of oxytocin is enhanced by estrogen in the mouse. Physiol Behav 60:1209–1215.  https://doi.org/10.1016/S0031-9384(96)00212-0 CrossRefPubMedGoogle Scholar
  67. McNaughton N, Ruan M, Woodnorth M-A (2006) Restoring theta-like rhythmicity in rats restores initial learning in the Morris water maze. Hippocampus 16:1102–1110.  https://doi.org/10.1002/hipo.20235 CrossRefPubMedGoogle Scholar
  68. Miyataa S, Ishiyamaa M, Shibatab M et al (1998) Infant cold exposure changes Fos expression to acute cold stimulation in adult hypothalamic brain regions. Neurosci Res 31:219–225.  https://doi.org/10.1016/S0168-0102(98)00045-5 CrossRefGoogle Scholar
  69. Mulkey RM, Malenka RC (1992) Mechanisms underlying induction of homosynaptic long-term depression in area CA1 of the hippocampus. Neuron 9:967–975.  https://doi.org/10.1016/0896-6273(92)90248-C CrossRefPubMedGoogle Scholar
  70. Murgatroyd C, Wigger A, Frank E et al (2004) Impaired repression at a vasopressin promoter polymorphism underlies overexpression of vasopressin in a Rat Model of Trait AnxietyGoogle Scholar
  71. Nakashiba T, Young JZ, McHugh TJ et al (2008) Transgenic inhibition of synaptic transmission reveals role of CA3 output in hippocampal learning. Science 319:1260–1264.  https://doi.org/10.1126/science.1151120 CrossRefPubMedGoogle Scholar
  72. Nakashiba T, Cushman JD, Pelkey KA et al (2012) Young dentate granule cells mediate pattern separation, whereas old granule cells facilitate pattern completion. Cell 149:188–201.  https://doi.org/10.1016/j.cell.2012.01.046 CrossRefPubMedPubMedCentralGoogle Scholar
  73. Nakazawa K, Quirk MC, Chitwood RA et al (2002) Requirement for hippocampal CA3 NMDA receptors in associative memory recall. Science 297:211–218.  https://doi.org/10.1126/science.1071795 CrossRefPubMedPubMedCentralGoogle Scholar
  74. Nasrallah K, Piskorowski RA, Chevaleyre V (2015) Inhibitory plasticity permits the recruitment of CA2 pyramidal neurons by CA3. eNeuro.  https://doi.org/10.1523/ENEURO.0049-15.2015 PubMedPubMedCentralGoogle Scholar
  75. Neumann ID, Landgraf R (2012) Balance of brain oxytocin and vasopressin: implications for anxiety, depression, and social behaviors. Trends Neurosci 35:649–659CrossRefPubMedGoogle Scholar
  76. Ochiishi T, Saitoh Y, Yukawa A et al (1999) High level of adenosine A1 receptor-like immunoreactivity in the CA2/CA3a region of the adult rat hippocampus. Neuroscience 93:955–967CrossRefPubMedGoogle Scholar
  77. Ostrowski NL, Lolait SJ, Young Iii WS (1994) Cellular localization of vasopressin Vla receptor messenger ribonucleic acid in adult male rat brain, pineal, and brain vasculature. Endocrinology 135:1511–1528.  https://doi.org/10.1210/endo.135.4.7925112 CrossRefPubMedGoogle Scholar
  78. Pagani JH, Zhao M, Cui Z et al (2015) Role of the vasopressin 1b receptor in rodent aggressive behavior and synaptic plasticity in hippocampal area CA2. Mol Psychiatry 20:490–499.  https://doi.org/10.1038/mp.2014.47 CrossRefPubMedGoogle Scholar
  79. Pan W-X, McNaughton N (2004) The supramammillary area: its organization, functions and relationship to the hippocampus. Prog Neurobiol 74:127–166.  https://doi.org/10.1016/j.pneurobio.2004.09.003 CrossRefPubMedGoogle Scholar
  80. Pikkarainen M, Ronkko S, Savander V et al (1999) Projections from the lateral, basal,and accessory basal nuclei of the amygdala to the hippocampal formation in rat. J Comp Neurol 403:229–260. https://doi.org/10.1002/(SICI)1096-9861(19990111)403:2<229::AID-CNE7>3.0.CO;2-PGoogle Scholar
  81. Piskorowski RA, Chevaleyre V (2013) Delta-opioid receptors mediate unique plasticity onto parvalbumin-expressing interneurons in area CA2 of the hippocampus. J Neurosci 33:14567–14578.  https://doi.org/10.1523/JNEUROSCI.0649-13.2013 CrossRefPubMedGoogle Scholar
  82. Piskorowski RA, Nasrallah K, Diamantopoulou A et al (2016) Age-dependent specific changes in area CA2 of the hippocampus and social memory deficit in a mouse model of the 22q11.2 deletion syndrome. Neuron 89:163–176.  https://doi.org/10.1016/j.neuron.2015.11.036 CrossRefPubMedPubMedCentralGoogle Scholar
  83. Prediger RDS, Takahashi RN (2005) Modulation of short-term social memory in rats by adenosine A1 and A2A receptors. Neurosci Lett 376:160–165.  https://doi.org/10.1016/j.neulet.2004.11.049 CrossRefPubMedGoogle Scholar
  84. Redondo RL, Morris RGM (2011) Making memories last: the synaptic tagging and capture hypothesis. Nat Rev Neurosci 12:17–30.  https://doi.org/10.1038/nrn2963 CrossRefPubMedGoogle Scholar
  85. Rowland DC, Weible AP, Wickersham IR et al (2013) Transgenically targeted rabies virus demonstrates a major monosynaptic projection from hippocampal area CA2 to medial entorhinal layer II neurons. J Neurosci 33:14889–14898.  https://doi.org/10.1523/JNEUROSCI.1046-13.2013 CrossRefPubMedPubMedCentralGoogle Scholar
  86. Sadowski M, Wisniewski HM, Jakubowska-Sadowska K et al (1999) Pattern of neuronal loss in the rat hippocampus following experimental cardiac arrest-induced ischemia. J Neurol Sci 168:13–20CrossRefPubMedGoogle Scholar
  87. Sajikumar S, Navakkode S, Korz V, Frey JU (2007) Cognitive and emotional information processing: protein synthesis and gene expression. J Physiol 584:389–400.  https://doi.org/10.1113/jphysiol.2007.140087 CrossRefPubMedPubMedCentralGoogle Scholar
  88. Sajikumar S, Morris RGM, Korte M (2014) Competition between recently potentiated synaptic inputs reveals a winner-take-all phase of synaptic tagging and capture. Proc Natl Acad Sci USA 111:12217–12221.  https://doi.org/10.1073/pnas.1403643111 CrossRefPubMedPubMedCentralGoogle Scholar
  89. Scoville WB, Milner B (1957) Loss of recent memory after bilateral hippocampal lesions. J Neuropsychiatry Clin Neurosci 20:11–21.  https://doi.org/10.1136/jnnp.20.1.11 Google Scholar
  90. Senitz D (1999) A reduction of nonpyramidal cells in sector CA2 of schizophrenics and manic depressives. Biol Psychiatry 45:1528–1530CrossRefPubMedGoogle Scholar
  91. Shetty MS, Sajikumar S (2017) “Tagging” along memories in aging: Synaptic tagging and capture mechanisms in the aged hippocampus. Ageing Res Rev 35:22–35.  https://doi.org/10.1016/J.ARR.2016.12.008 CrossRefGoogle Scholar
  92. Simons SB, Escobedo Y, Yasuda R, Dudek SM (2009) Regional differences in hippocampal calcium handling provide a cellular mechanism for limiting plasticity. Proc Natl Acad Sci 106:14080–14084.  https://doi.org/10.1073/pnas.0904775106 CrossRefPubMedPubMedCentralGoogle Scholar
  93. Simons SB, Caruana DA, Zhao M, Dudek SM (2011) Caffeine-induced synaptic potentiation in hippocampal CA2 neurons. Nat Neurosci 15:23–25.  https://doi.org/10.1038/nn.2962 CrossRefPubMedPubMedCentralGoogle Scholar
  94. Smith AS, Williams Avram SK, Cymerblit-Sabba A et al (2016) Targeted activation of the hippocampal CA2 area strongly enhances social memory. Mol Psychiatry 21:1137–1144.  https://doi.org/10.1038/mp.2015.189 CrossRefPubMedPubMedCentralGoogle Scholar
  95. Stevenson EL, Caldwell HK (2014) Lesions to the CA2 region of the hippocampus impair social memory in mice. Eur J Neurosci 40:3294–3301.  https://doi.org/10.1111/ejn.12689 CrossRefPubMedPubMedCentralGoogle Scholar
  96. Talley EM, Solorzano G, Lei Q et al (2001) Cns distribution of members of the two-pore-domain (KCNK) potassium channel family. J Neurosci 21:7491–7505PubMedGoogle Scholar
  97. Tamamaki N, Abe K, Nojyo Y (1988) Three-dimensional analysis of the whole axonal arbors originating from single CA2 pyramidal neurons in the rat hippocampus with the aid of a computer graphic technique. Brain Res 452:255–272.  https://doi.org/10.1016/0006-8993(88)90030-3 CrossRefPubMedGoogle Scholar
  98. Tsien JZ, Huerta PT, Tonegawa S (1996) The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memory. Cell 87:1327–1338CrossRefPubMedGoogle Scholar
  99. van Strien NM, Cappaert NLM, Witter MP (2009) The anatomy of memory: an interactive overview of the parahippocampal–hippocampal network. Nat Rev Neurosci 10:272–282.  https://doi.org/10.1038/nrn2614 CrossRefPubMedGoogle Scholar
  100. Wersinger SR, Ginns EI, O’Carroll A-M et al (2002) Vasopressin V1b receptor knockout reduces aggressive behavior in male mice. Mol Psychiatry 7:975–984.  https://doi.org/10.1038/sj.mp.4001195 CrossRefPubMedGoogle Scholar
  101. Windle RJ, Shanks N, Lightman SL, Ingram CD (1997) Central oxytocin administration reduces stress-induced corticosterone release and anxiety behavior in rats. Endocrinology 138:2829–2834.  https://doi.org/10.1210/endo.138.7.5255 CrossRefPubMedGoogle Scholar
  102. Yeckel MF, Berger TW (1990) Feedforward excitation of the hippocampus by afferents from the entorhinal cortex: redefinition of the role of the trisynaptic pathway. Proc Natl Acad Sci USA 87:5832–5836.  https://doi.org/10.1073/PNAS.87.15.5832 CrossRefPubMedPubMedCentralGoogle Scholar
  103. Yohn CN, Gergues MM, Samuels BA (2017) The role of 5-HT receptors in depression. Mol Brain 10:28.  https://doi.org/10.1186/s13041-017-0306-y CrossRefPubMedPubMedCentralGoogle Scholar
  104. Yoshida M, Takayanagi Y, Inoue K et al (2009) Evidence that oxytocin exerts anxiolytic effects via oxytocin receptor expressed in serotonergic neurons in mice. J Neurosci 29:2259–2271.  https://doi.org/10.1523/JNEUROSCI.5593-08.2009 CrossRefPubMedGoogle Scholar
  105. Young WS, Li J, Wersinger SR, Palkovits M (2006) The vasopressin 1b receptor is prominent in the hippocampal area CA2 where it is unaffected by restraint stress or adrenalectomy. Neuroscience 143:1031–1039.  https://doi.org/10.1016/j.neuroscience.2006.08.040 CrossRefPubMedPubMedCentralGoogle Scholar
  106. Zalcman SS, Siegel A (2006) The neurobiology of aggression and rage: Role of cytokines. Brain Behav Immun 20:507–514.  https://doi.org/10.1016/J.BBI.2006.05.002 CrossRefPubMedGoogle Scholar
  107. Zhang L, Hernández VS (2013) Synaptic innervation to rat hippocampus by vasopressin-immuno-positive fibres from the hypothalamic supraoptic and paraventricular nuclei. Neuroscience 228:139–162.  https://doi.org/10.1016/j.neuroscience.2012.10.010 CrossRefPubMedGoogle Scholar
  108. Zhang ZJ, Reynolds GP (2002) A selective decrease in the relative density of parvalbumin-immunoreactive neurons in the hippocampus in schizophrenia. Schizophr Res 55:1–10CrossRefPubMedGoogle Scholar
  109. Zhao M, Choi Y-S, Obrietan K, Dudek SM (2007) Synaptic plasticity (and the lack thereof) in hippocampal CA2 neurons. J Neurosci 27:12025–12032.  https://doi.org/10.1523/JNEUROSCI.4094-07.2007 CrossRefPubMedGoogle Scholar
  110. Zingg HH (1996) Vasopressin and oxytocin receptors. Baillieres Clin Endocrinol Metab 10:75–96CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Physiology, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
  2. 2.Neurobiology/Aging Program, Life Sciences Institute (LSI)National University of SingaporeSingaporeSingapore

Personalised recommendations