Advertisement

Brain Structure and Function

, Volume 223, Issue 9, pp 4099–4113 | Cite as

Hippocampal proBDNF facilitates place learning strategy associated with neural activity in rats

  • Lei AnEmail author
  • Xiaoliang Li
  • Chunzhi Tang
  • Nenggui Xu
  • Wei SunEmail author
Original Article

Abstract

Mature brain-derived neurotrophic factor has been shown to have a promotive effect on synaptic plasticity and spatial memory. The precursor of BDNF (proBDNF) has emerged as a protein against its mature form. However, it is unknown whether and how proBDNF regulates neural excitability and spatial behavior. Through infusion of cleavage-resistant proBDNF or its antibody into HPC, we sought evidence for the influences by employing multiple behavioral tests and recording hippocampal single-unit activity. Our behavioral findings showed that proBDNF induced beneficial effects on spatial learning by facilitating the use of the place strategy and inhibiting the response strategy, including (1) using more place search strategies but less response strategies, and (2) increasing the number of rats in choosing place strategies but not response strategies. Intriguingly, infusion of an anti-proBDNF antibody did not affect rats’ training process but rendered the adaption to learning reversal training more difficult, indicating deficits in choosing the proper learning strategy. The training-induced increase in proBDNF promoted the firing rate of pyramidal neurons but not fast-spiking (FS) interneurons. Importantly, endogenous proBDNF facilitated the neural correlate of spatial, but not response, learning behavior. However, the anti-proBDNF antibody effectively reversed the strategy preference and inhibited neural activity. We herein propose that proBDNF exerts pivotal effects on neural excitability and the use of cognitive strategies to facilitate the spatial learning process.

Keywords

Hippocampus Learning strategy Neural activity ProBDNF 

Abbreviations

cAMP

Adenosine 3′:5′cyclic monophosphate

CNS

Central nervous system

CREB

cAMP response-element binding protein

ERK

cAMP response-element binding protein (pCREB)

FS

Fast-spiking

HPC

Hippocampus

LTD

Long-term depression

mBDNF

Mature brain-derived neurotrophic factor

MWM

Morris water maze

proBDNF

The precursor of mature brain-derived neurotrophic factor

pCREB

Phosphorylation of cAMP response-element binding protein

tPA

Issue plasminogen activator

TrkB

Tropomyosin receptor kinase B

Notes

Acknowledgements

A special acknowledgement is due to Dr. Andrew Roebuck who has offered professional support in language polishing and editing, and valuable comments on the revised versions of the manuscript. This work was supported by Grants from the National Natural Science Foundation of China 31700929 to L.A.

Author contributions

Conceived and designed the experiments: LA, WS, CZT, NGX and XLL; performed the experiments LA, XLL and WS; analyzed the data: LA, XLL; wrote the manuscript: LA, WS.

Compliance with ethical standards

Conflict of interest

There is not a conflict of interest for authors.

Ethics statement

All procedures were done in accordance with ethical guidelines laid down by the ethics Committee on the Care and Use of Animals Committee of Guangzhou University of Chinese Medicine.

Supplementary material

429_2018_1742_MOESM1_ESM.pdf (647 kb)
Supplementary material 1 (PDF 646 KB)

References

  1. Agarwal G, Stevenson IH, Berenyi A, Mizuseki K, Buzsaki G, Sommer FT (2014) Spatially distributed local fields in the hippocampus encode rat position. Science 344(6184):626–630PubMedPubMedCentralGoogle Scholar
  2. An L, Sun W (2018) Acute melamine affects spatial memory consolidation via inhibiting hippocampal NMDAR-dependent LTD in rats. Toxicol Sci 163(2):385–396PubMedGoogle Scholar
  3. Bai YY, Ruan CS, Yang CR, Li JY, Kang ZL, Zhou L, Liu D, Zeng YQ, Wang TH, Tian CF, Liao H, Bobrovskaya L, Zhou XF (2016) ProBDNF signaling regulates depression-like behaviors in rodents under chronic stress. Neuropsychopharmacology 41(12):2882–2892PubMedPubMedCentralGoogle Scholar
  4. Balschun D, Wolfer DP, Gass P, Mantamadiotis T, Welzl H, Schutz G, Frey JU, Lipp HP (2003) Does cAMP response element-binding protein have a pivotal role in hippocampal synaptic plasticity and hippocampus-dependent memory? J Neurosci 23(15):6304–6314PubMedGoogle Scholar
  5. Barnes P, Thomas KL (2008) Proteolysis of proBDNF is a key regulator in the formation of memory. PLoS One 3(9):e3248PubMedPubMedCentralGoogle Scholar
  6. Barrett GL, Reid CA, Tsafoulis C, Zhu W, Williams DA, Paolini AG, Trieu J, Murphy M (2010) Enhanced spatial memory and hippocampal long-term potentiation in p75 neurotrophin receptor knockout mice. Hippocampus 20(1):145–152PubMedGoogle Scholar
  7. Bekinschtein P, Cammarota M, Katche C, Slipczuk L, Rossato JI, Goldin A, Izquierdo I, Medina JH (2008) BDNF is essential to promote persistence of long-term memory storage. Proc Natl Acad Sci 105(7):2711–2716PubMedGoogle Scholar
  8. Bekinschtein P, Cammarota M, Medina JH (2014) BDNF and memory processing. Neuropharmacology 76 Pt C:677–683Google Scholar
  9. Bramham CR, Messaoudi E (2005) BDNF function in adult synaptic plasticity: the synaptic consolidation hypothesis. Prog Neurobiol 76(2):99–125PubMedGoogle Scholar
  10. Broicher T, Malerba P, Dorval AD, Borisyuk A, Fernandez FR, White JA (2012) Spike phase locking in CA1 pyramidal neurons depends on background conductance and firing rate. J Neurosci 32(41):14374–14388PubMedGoogle Scholar
  11. Bygrave AM, Masiulis S, Nicholson E, Berkemann M, Barkus C, Sprengel R, Harrison PJ, Kullmann DM, Bannerman DM, Katzel D (2016) Knockout of NMDA-receptors from parvalbumin interneurons sensitizes to schizophrenia-related deficits induced by MK-801. Transl Psychiatry 6:e778PubMedPubMedCentralGoogle Scholar
  12. Cacquevel M, Launay S, Castel H, Benchenane K, Chéenne S, Buée L, Moons L, Delacourte A, Carmeliet P, Vivien D (2007) Ageing and amyloid-beta peptide deposition contribute to an impaired brain tissue plasminogen activator activity by different mechanisms. Neurobiol Dis 27(2):164–173PubMedGoogle Scholar
  13. Cahill JF, Baxter MG (2001) Cholinergic and noncholinergic septal neurons modulate strategy selection in spatial learning. Eur J Neurosci 14(11):1856–1864PubMedGoogle Scholar
  14. Cao W, Duan J, Wang X, Zhong X, Hu Z, Huang F, Wang H, Zhang J, Li F, Luo X, Li CQ (2014) Early enriched environment induces an increased conversion of proBDNF to BDNF in the adult rat’s hippocampus. Behav Brain Res 265:76–83PubMedGoogle Scholar
  15. Chen J, Li CR, Yang H, Liu J, Zhang T, Jiao SS, Wang YJ, Xu ZQ (2016) proBDNF attenuates hippocampal neurogenesis and induces learning and memory deficits in aged mice. Neurotox Res 29(1):47–53PubMedGoogle Scholar
  16. Chen J, Zhang T, Jiao S, Zhou X, Zhong J, Wang Y, Liu J, Deng J, Wang S, Xu Z (2017) proBDNF accelerates brain amyloid-beta deposition and learning and memory impairment in APPswePS1dE9 transgenic mice. J Alzheimers Dis 59(3):941–949PubMedGoogle Scholar
  17. Cho WH, Han JS (2016) Differences in the flexibility of switching learning strategies and CREB phosphorylation levels in prefrontal cortex, dorsal striatum and hippocampus in two inbred strains of mice. Front Behav Neurosci 10:176PubMedPubMedCentralGoogle Scholar
  18. Colombo PJ, Brightwell JJ, Countryman RA (2003) Cognitive strategy-specific increases in phosphorylated cAMP response element-binding protein and c-Fos in the hippocampus and dorsal striatum. J Neurosci 23(8):3547–3554PubMedGoogle Scholar
  19. D’Amore DE, Tracy BA, Parikh V (2013) Exogenous BDNF facilitates strategy set-shifting by modulating glutamate dynamics in the dorsal striatum. Neuropharmacology 75:312–323PubMedGoogle Scholar
  20. DeCoteau WE, Thorn C, Gibson DJ, Courtemanche R, Mitra P, Kubota Y, Graybiel AM (2007) Learning-related coordination of striatal and hippocampal theta rhythms during acquisition of a procedural maze task. Proc Natl Acad Sci USA 104(13):5644–5649PubMedGoogle Scholar
  21. Deinhardt K, Chao MV (2014) Shaping neurons: long and short range effects of mature and proBDNF signalling upon neuronal structure. Neuropharmacology 76 Pt C:603–609PubMedGoogle Scholar
  22. Delcasso S, Huh N, Byeon JS, Lee J, Jung MW, Lee I (2014) Functional relationships between the hippocampus and dorsomedial striatum in learning a visual scene-based memory task in rats. J Neurosci 34(47):15534–15547PubMedPubMedCentralGoogle Scholar
  23. Dong Z, Gong B, Li H, Bai Y, Wu X, Huang Y, He W, Li T, Wang YT (2012) Mechanisms of hippocampal long-term depression are required for memory enhancement by novelty exploration. J Neurosci 32(35):11980–11990PubMedPubMedCentralGoogle Scholar
  24. Dong Z, Bai Y, Wu X, Li H, Gong B, Howland JG, Huang Y, He W, Li T, Wang YT (2013) Hippocampal long-term depression mediates spatial reversal learning in the Morris water maze. Neuropharmacology 64:65–73PubMedGoogle Scholar
  25. Dougherty KD, Milner TA (1999) p75NTR immunoreactivity in the rat dentate gyrus is mostly within presynaptic profiles but is also found in some astrocytic and postsynaptic profiles. J Comp Neurol 407(1):77–91PubMedGoogle Scholar
  26. Fan YJ, Wu LL, Li HY, Wang YJ, Zhou XF (2008) Differential effects of pro-BDNF on sensory neurons after sciatic nerve transection in neonatal rats. Eur J Neurosci 27(9):2380–2390PubMedGoogle Scholar
  27. Ferbinteanu J (2016) Contributions of hippocampus and striatum to memory-guided behavior depend on past experience. J Neurosci 36(24):6459–6470PubMedPubMedCentralGoogle Scholar
  28. Fiorentino H, Kuczewski N, Diabira D, Ferrand N, Pangalos MN, Porcher C, Gaiarsa JL (2009) GABA(B) receptor activation triggers BDNF release and promotes the maturation of GABAergic synapses. J Neurosci 29(37):11650–11661PubMedGoogle Scholar
  29. Garthe A, Behr J, Kempermann G (2009) Adult-generated hippocampal neurons allow the flexible use of spatially precise learning strategies. PLoS One 4(5):e5464PubMedPubMedCentralGoogle Scholar
  30. Garthe A, Roeder I, Kempermann G (2016) Mice in an enriched environment learn more flexibly because of adult hippocampal neurogenesis. Hippocampus 26(2):261–271PubMedGoogle Scholar
  31. Gibon J, Buckley SM, Unsain N, Kaartinen V, Seguela P, Barker PA (2015) proBDNF and p75NTR control excitability and persistent firing of cortical pyramidal neurons. J Neurosci 35(26):9741–9753PubMedGoogle Scholar
  32. Gourley SL, Koleske AJ, Taylor JR (2009) Loss of dendrite stabilization by the Abl-related gene (Arg) kinase regulates behavioral flexibility and sensitivity to cocaine. Proc Natl Acad Sci USA 106(39):16859–16864PubMedGoogle Scholar
  33. Gourley SL, Olevska A, Warren MS, Taylor JR, Koleske AJ (2012) Arg kinase regulates prefrontal dendritic spine refinement and cocaine-induced plasticity. J Neurosci 32(7):2314–2323PubMedPubMedCentralGoogle Scholar
  34. Greenberg ME, Xu B, Lu B, Hempstead BL (2009) New insights in the biology of BDNF synthesis and release: implications in CNS function. J Neurosci 29(41):12764–12767PubMedPubMedCentralGoogle Scholar
  35. Haege S, Galetzka D, Zechner U, Haaf T, Gamerdinger M, Behl C, Hiemke C, Schmitt U (2010) Spatial learning and expression patterns of PP1 mRNA in mouse hippocampus. Neuropsychobiology 61(4):188–196PubMedGoogle Scholar
  36. Hagewoud R, Havekes R, Tiba PA, Novati A, Hogenelst K, Weinreder P, Van der Zee EA, Meerlo P (2010) Coping with sleep deprivation: shifts in regional brain activity and learning strategy. Sleep 33(11):1465–1473PubMedPubMedCentralGoogle Scholar
  37. Harvey DR, McGauran AM, Murphy J, Burns L, McMonagle E, Commins S (2008) Emergence of an egocentric cue guiding and allocentric inferring strategy that mirrors hippocampal brain-derived neurotrophic factor (BDNF) expression in the Morris water maze. Neurobiol Learn Mem 89(4):462–479PubMedGoogle Scholar
  38. Harvey DR, Brant L, Commins S (2009) Differences in cue-dependent spatial navigation may be revealed by in-depth swimming analysis. Behav Processes 82(2):190–197PubMedGoogle Scholar
  39. Hernandez LF, Kubota Y, Hu D, Howe MW, Lemaire N, Graybiel AM (2013) Selective effects of dopamine depletion and L-DOPA therapy on learning-related firing dynamics of striatal neurons. J Neurosci 33(11):4782–4795PubMedPubMedCentralGoogle Scholar
  40. Holm MM, Nieto-Gonzalez JL, Vardya I, Vaegter CB, Nykjaer A, Jensen K (2009) Mature BDNF, but not proBDNF, reduces excitability of fast-spiking interneurons in mouse dentate gyrus. J Neurosci 29(40):12412–12418PubMedGoogle Scholar
  41. Je HS, Yang F, Ji Y, Nagappan G, Hempstead BL, Lu B (2012) Role of pro-brain-derived neurotrophic factor (proBDNF) to mature BDNF conversion in activity-dependent competition at developing neuromuscular synapses. Proc Natl Acad Sci USA 109(39):15924–15929PubMedGoogle Scholar
  42. Kathirvelu B, Colombo PJ (2013) Effects of lentivirus-mediated CREB expression in the dorsolateral striatum: memory enhancement and evidence for competitive and cooperative interactions with the hippocampus. Hippocampus 23(11):1066–1074.  https://doi.org/10.1002/hipo.22188 CrossRefPubMedGoogle Scholar
  43. Kealy J, Commins S (2009) Antagonism of glutamate receptors in the CA1 to perirhinal cortex projection prevents long-term potentiation and attenuates levels of brain-derived neurotrophic factor. Brain Res 1265:53–64PubMedGoogle Scholar
  44. Kemp A, Manahan-Vaughan D (2007) Hippocampal long-term depression: master or minion in declarative memory processes? Trends Neurosci 30(3):111–118PubMedGoogle Scholar
  45. Kim JJ, Baxter MG (2001) Multiple brain-memory systems: the whole does not equal the sum of its parts. Trends Neurosci 24(6):324–330PubMedGoogle Scholar
  46. Kim DH, Kim JM, Park SJ, Cai M, Liu X, Lee S, Shin CY, Ryu JH (2012) GABA(A) receptor blockade enhances memory consolidation by increasing hippocampal BDNF levels. Neuropsychopharmacology 37(2):422–433PubMedGoogle Scholar
  47. Kosaki Y, Pearce JM, McGregor A (2018) The response strategy and the place strategy in a plus-maze have different sensitivities to devaluation of expected outcome. Hippocampus.  https://doi.org/10.1002/hipo.22847 CrossRefPubMedPubMedCentralGoogle Scholar
  48. Kuipers SD, Bramham CR (2006) Brain-derived neurotrophic factor mechanisms and function in adult synaptic plasticity: new insights and implications for therapy. Curr Opin Drug Discov Dev 9(5):580–586Google Scholar
  49. Lee I, Kim J (2010) The shift from a response strategy to object-in-place strategy during learning is accompanied by a matching shift in neural firing correlates in the hippocampus. Learn Mem 17(8):381–393PubMedPubMedCentralGoogle Scholar
  50. Lee AS, Duman RS, Pittenger C (2008) A double dissociation revealing bidirectional competition between striatum and hippocampus during learning. Proc Natl Acad Sci USA 105(44):17163–17168PubMedGoogle Scholar
  51. Leutgeb S, Leutgeb JK, Barnes CA, Moser EI, McNaughton BL, Moser MB (2005) Independent codes for spatial and episodic memory in hippocampal neuronal ensembles. Science 309(5734):619–623PubMedGoogle Scholar
  52. Li JY, Liu J, Manaph NPA, Bobrovskaya L, Zhou XF (2017) ProBDNF inhibits proliferation, migration and differentiation of mouse neural stem cells. Brain Res 1668:46–55PubMedGoogle Scholar
  53. Lu B, Pang PT, Woo NH (2005) The yin and yang of neurotrophin action. Nat Rev Neurosci 6(8):603–614PubMedGoogle Scholar
  54. Lu B, Nagappan G, Guan X, Nathan PJ, Wren P (2013) BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases. Nat Rev Neurosci 14(6):401–416PubMedGoogle Scholar
  55. Lubin FD, Roth TL, Sweatt JD (2008) Epigenetic regulation of BDNF gene transcription in the consolidation of fear memory. J Neurosci 28(42):10576–10586PubMedPubMedCentralGoogle Scholar
  56. Ma Q, Yang J, Li T, Milner TA, Hempstead BL (2015) Selective reduction of striatal mature BDNF without induction of proBDNF in the zQ175 mouse model of Huntington’s disease. Neurobiol Dis 82:466–477PubMedPubMedCentralGoogle Scholar
  57. Martel G, Millard A, Jaffard R, Guillou JL (2006) Stimulation of hippocampal adenylyl cyclase activity dissociates memory consolidation processes for response and place learning. Learn Mem 13(3):342–348PubMedPubMedCentralGoogle Scholar
  58. Meis S, Endres T, Munsch T, Lessmann V (2017) The relation between long-term synaptic plasticity at glutamatergic synapses in the amygdala and fear learning in adult heterozygous BDNF-knockout mice. Cereb Cortex 28:1–14Google Scholar
  59. Miller JF, Neufang M, Solway A, Brandt A, Trippel M, Mader I, Hefft S, Merkow M, Polyn SM, Jacobs J, Kahana MJ, Schulze-Bonhage A (2013) Neural activity in human hippocampal formation reveals the spatial context of retrieved memories. Science 342(6162):1111–1114PubMedPubMedCentralGoogle Scholar
  60. Mizuseki K, Sirota A, Pastalkova E, Buzsaki G (2009) Theta oscillations provide temporal windows for local circuit computation in the entorhinal-hippocampal loop. Neuron 64(2):267–280PubMedPubMedCentralGoogle Scholar
  61. Orsini CA, Maren S (2012) Neural and cellular mechanisms of fear and extinction memory formation. Neurosci Biobehav Rev 36(7):1773–1802PubMedPubMedCentralGoogle Scholar
  62. Packard MG, McGaugh JL (1996) Inactivation of hippocampus or caudate nucleus with lidocaine differentially affects expression of place and response learning. Neurobiol Learn Mem 65(1):65–72PubMedGoogle Scholar
  63. Perovic M, Tesic V, Mladenovic Djordjevic A, Smiljanic K, Loncarevic-Vasiljkovic N, Ruzdijic S, Kanazir S (2013) BDNF transcripts, proBDNF and proNGF, in the cortex and hippocampus throughout the life span of the rat. Age (Dordr) 35(6):2057–2070Google Scholar
  64. Regier PS, Amemiya S, Redish AD (2015) Hippocampus and subregions of the dorsal striatum respond differently to a behavioral strategy change on a spatial navigation task. J Neurophysiol 114(3):1399–1416PubMedPubMedCentralGoogle Scholar
  65. Rogers J, Churilov L, Hannan AJ, Renoir T (2017) Search strategy selection in the Morris water maze indicates allocentric map formation during learning that underpins spatial memory formation. Neurobiol Learn Mem 139:37–49PubMedGoogle Scholar
  66. Rutten K, Wallace TL, Works M, Prickaerts J, Blokland A, Novak TJ, Santarelli L, Misner DL (2011) Enhanced long-term depression and impaired reversal learning in phosphodiesterase 4B-knockout (PDE4B−/−) mice. Neuropharmacology 61(1–2):138–147PubMedGoogle Scholar
  67. Santini E, Huynh TN, MacAskill AF, Carter AG, Pierre P, Ruggero D, Kaphzan H, Klann E (2013) Exaggerated translation causes synaptic and behavioural aberrations associated with autism. Nature 493(7432):411–415PubMedGoogle Scholar
  68. Schomburg EW, Anastassiou CA, Buzsaki G, Koch C (2012) The spiking component of oscillatory extracellular potentials in the rat hippocampus. J Neurosci 32(34):11798–11811PubMedPubMedCentralGoogle Scholar
  69. Schreiweis C, Bornschein U, Burguiere E, Kerimoglu C, Schreiter S, Dannemann M, Goyal S, Rea E, French CA, Puliyadi R, Groszer M, Fisher SE, Mundry R, Winter C, Hevers W, Paabo S, Enard W, Graybiel AM (2014) Humanized Foxp2 accelerates learning by enhancing transitions from declarative to procedural performance. Proc Natl Acad Sci USA 111(39):14253–14258PubMedGoogle Scholar
  70. Segawa M, Morinobu S, Matsumoto T, Fuchikami M, Yamawaki S (2013) Electroconvulsive seizure, but not imipramine, rapidly up-regulates pro-BDNF and t-PA, leading to mature BDNF production, in the rat hippocampus. Int J Neuropsychopharmacol 16(2):339–350PubMedGoogle Scholar
  71. Silhol M, Arancibia S, Maurice T, Tapia-Arancibia L (2007) Spatial memory training modifies the expression of brain-derived neurotrophic factor tyrosine kinase receptors in young and aged rats. Neuroscience 146(3):962–973PubMedGoogle Scholar
  72. Smith DM, Mizumori SJ (2006) Learning-related development of context-specific neuronal responses to places and events: the hippocampal role in context processing. J Neurosci 26(12):3154–3163PubMedGoogle Scholar
  73. Stark E, Roux L, Eichler R, Senzai Y, Royer S, Buzsaki G (2014) Pyramidal cell-interneuron interactions underlie hippocampal ripple oscillations. Neuron 83(2):467–480PubMedPubMedCentralGoogle Scholar
  74. Stone SS, Teixeira CM, Devito LM, Zaslavsky K, Josselyn SA, Lozano AM, Frankland PW (2011) Stimulation of entorhinal cortex promotes adult neurogenesis and facilitates spatial memory. J Neurosci 31(38):13469–13484PubMedGoogle Scholar
  75. Sun Y, Lim Y, Li F, Liu S, Lu JJ, Haberberger R, Zhong JH, Zhou XF (2012) ProBDNF collapses neurite outgrowth of primary neurons by activating RhoA. PLoS One 7(4):e35883PubMedPubMedCentralGoogle Scholar
  76. Sun W, Li X, An L (2018) Distinct roles of prelimbic and infralimbic proBDNF in extinction of conditioned fear. Neuropharmacology 131:11–19PubMedGoogle Scholar
  77. Thorn CA, Atallah H, Howe M, Graybiel AM (2010) Differential dynamics of activity changes in dorsolateral and dorsomedial striatal loops during learning. Neuron 66(5):781–795PubMedPubMedCentralGoogle Scholar
  78. Tort AB, Kramer MA, Thorn C, Gibson DJ, Kubota Y, Graybiel AM, Kopell NJ (2008) Dynamic cross-frequency couplings of local field potential oscillations in rat striatum and hippocampus during performance of a T-maze task. Proc Natl Acad Sci USA 105(51):20517–20522PubMedGoogle Scholar
  79. Tsetsenis T, Younts TJ, Chiu CQ, Kaeser PS, Castillo PE, Sudhof TC (2011) Rab3B protein is required for long-term depression of hippocampal inhibitory synapses and for normal reversal learning. Proc Natl Acad Sci USA 108(34):14300–14305PubMedGoogle Scholar
  80. Tyler WJ, Alonso M, Bramham CR, Pozzo-Miller LD (2002) From acquisition to consolidation: on the role of brain-derived neurotrophic factor signaling in hippocampal-dependent learning. Learn Mem 9(5):224–237PubMedPubMedCentralGoogle Scholar
  81. Vila-Ballo A, Mas-Herrero E, Ripolles P, Simo M, Miro J, Cucurell D, Lopez-Barroso D, Juncadella M, Marco-Pallares J, Falip M, Rodriguez-Fornells A (2017) Unraveling the role of the hippocampus in reversal learning. J Neurosci 37(28):6686–6697PubMedGoogle Scholar
  82. Vorhees CV, Williams MT (2006) Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc 1(2):848–858PubMedPubMedCentralGoogle Scholar
  83. Watts A, Gritton HJ, Sweigart J, Poe GR (2012) Antidepressant suppression of non-REM sleep spindles and REM sleep impairs hippocampus-dependent learning while augmenting striatum-dependent learning. J Neurosci 32(39):13411–13420PubMedPubMedCentralGoogle Scholar
  84. Wingard JC, Goodman J, Leong KC, Packard MG (2015) Differential effects of massed and spaced training on place and response learning: a memory systems perspective. Behav Processes 118:85–89PubMedGoogle Scholar
  85. Woo NH, Teng HK, Siao CJ, Chiaruttini C, Pang PT, Milner TA, Hempstead BL, Lu B (2005) Activation of p75NTR by proBDNF facilitates hippocampal long-term depression. Nat Neurosci 8(8):1069–1077PubMedGoogle Scholar
  86. Xu ZQ, Sun Y, Li HY, Lim Y, Zhong JH, Zhou XF (2011) Endogenous proBDNF is a negative regulator of migration of cerebellar granule cells in neonatal mice. Eur J Neurosci 33(8):1376–1384PubMedGoogle Scholar
  87. Yang F, Je HS, Ji Y, Nagappan G, Hempstead B, Lu B (2009) Pro-BDNF-induced synaptic depression and retraction at developing neuromuscular synapses. J Cell Biol 185(4):727–741PubMedPubMedCentralGoogle Scholar
  88. Yang J, Harte-Hargrove LC, Siao CJ, Marinic T, Clarke R, Ma Q, Jing D, Lafrancois JJ, Bath KG, Mark W, Ballon D, Lee FS, Scharfman HE, Hempstead BL (2014) proBDNF negatively regulates neuronal remodeling, synaptic transmission, and synaptic plasticity in hippocampus. Cell Rep 7(3):796–806PubMedPubMedCentralGoogle Scholar
  89. Yeh CM, Huang CC, Hsu KS (2012) Prenatal stress alters hippocampal synaptic plasticity in young rat offspring through preventing the proteolytic conversion of pro-brain-derived neurotrophic factor (BDNF) to mature BDNF. J Physiol 590(Pt 4):991–1010PubMedGoogle Scholar
  90. Zeamer A, Heuer E, Bachevalier J (2010) Developmental trajectory of object recognition memory in infant rhesus macaques with and without neonatal hippocampal lesions. J Neurosci 30(27):9157–9165PubMedPubMedCentralGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Medical College of Acupuncture-Moxibustion and RehabilitationGuangzhou University of Chinese MedicineGuangzhouChina
  2. 2.College of Acupuncture-Moxibustion and OrthopedicsGuiyang University of Chinese MedicineGuiyangChina
  3. 3.Department of PhysiologyUniversity of SaskatchewanSaskatoonCanada

Personalised recommendations