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Neurogenesis Inhibition Prevents Enriched Environment to Prolong and Strengthen Social Recognition Memory, But Not to Increase BDNF Expression

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Abstract

Hippocampus-dependent memories, such as social recognition (SRM), are modulated by neurogenesis. However, the precise role of newborn neurons in social memory processing is still unknown. We showed previously that 1 week of enriched environment (EE) is sufficient to increase neurogenesis in the hippocampus (HIP) and the olfactory bulb (OB) of mice. Here, we tested the hypothesis that 1 week of EE would enhance SRM persistence and strength. In addition, as brain-derived neurotrophic factor (BDNF) may mediate some of the neurogenesis effects on memory, we also tested if 1 week of EE would increase BDNF expression in the HIP and OB. We also predicted that neurogenesis inhibition would block the gain of function caused by EE on both SRM and BDNF expression. We found that EE increased BDNF expression in the HIP and OB of mice; at the same time, it allowed SRM to last longer. In addition, mice on EE had their SRM unaffected by memory consolidation interferences. As we predicted, treatment with the anti-mitotic drug AraC blocked EE effects on SRM. Surprisingly, neurogenesis inhibition did not affect the BDNF expression, increased by EE. Together, our results suggest that newborn neurons improve SRM persistence through a BDNF-independent mechanism. Interestingly, this study on social memory uncovered an unexpected dissociation between the effect of adult neurogenesis and BDNF expression on memory persistence, reassuring the idea that not all neurogenesis effects on memory are BDNF-dependent.

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References

  1. Gheusi G, Lledo PM (2014) Adult neurogenesis in the olfactory system shapes odor memory and perception. Prog Brain Res 208:157–175

    Article  PubMed  Google Scholar 

  2. Deng W, Aimone JB, Gage FH (2010) New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat Rev Neurosci 11(5):339–350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Schinder AF, Gage FH (2004) A hypothesis about the role of adult neurogenesis in hippocampal function. Physiology (Bethesda) 19:253–261

    Article  Google Scholar 

  4. Aimone JB, Deng W, Gage FH (2011) Resolving new memories: a critical look at the dentate gyrus, adult neurogenesis, and pattern separation. Neuron 70(4):589–596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Scharfman H, Goodman J, Macleod A, Phani S, Antonelli C, Croll S (2005) Increased neurogenesis and the ectopic granule cells after intrahippocampal BDNF infusion in adult rats. Exp Neurol 192(2):348–356

    Article  CAS  PubMed  Google Scholar 

  6. Bekinschtein P, Kent BA, Oomen CA, Clemenson GD, Gage FH, Saksida LM, Bussey TJ (2013) BDNF in the dentate gyrus is required for consolidation of “pattern-separated” memories. Cell Rep 5(3):759–768

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Bekinschtein P, Kent BA, Oomen CA, Clemenson GD, Gage FH, Saksida LM, Bussey TJ, (2014) Brain-derived neurotrophic factor interacts with adult-born immature cells in the dentate gyrus. doi: 10.1002/hipo.22304

  8. Kogan JH, Frankland PW, Silva AJ (2000) Long-term memory underlying hippocampus-dependent social recognition in mice. Hippocampus 10(1):47–56

    Article  CAS  PubMed  Google Scholar 

  9. Pena RR, Pereira-Caixeta AR, Moraes MF, Pereira GS (2014) Anisomycin administered in the olfactory bulb and dorsal hippocampus impaired social recognition memory consolidation in different time-points. Brain Res Bull 109:151–157

    Article  CAS  PubMed  Google Scholar 

  10. Monteiro BM, Moreira FA, Massensini AR, Moraes MF, Pereira GS (2014) Enriched environment increases neurogenesis and improves social memory persistence in socially isolated adult mice. Hippocampus 24(2):239–248

    Article  PubMed  Google Scholar 

  11. Richter K, Wolf G, Engelmann M (2005) Social recognition memory requires two stages of protein synthesis in mice. Learn Mem 12(4):407–413

    Article  PubMed  PubMed Central  Google Scholar 

  12. Steru L, Chermat R, Thierry B, Simon P (1985) The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology (Berlin) 85(3):367–370

    Article  CAS  Google Scholar 

  13. Bruel-Jungerman E, Laroche S, Rampon C (2005) New neurons in the dentate gyrus are involved in the expression of enhanced long-term memory following environmental enrichment. Eur J Neurosci 21(2):513–521

    Article  PubMed  Google Scholar 

  14. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  15. Paxinos G, Franklin KBJ (2011) The mouse brain in stereotaxic coordinates, 2nd edn. Academic, San Diego

    Google Scholar 

  16. Mileva GR, Bielajew C (2015) Environmental manipulation affects depressive-like behaviours in female Wistar-Kyoto rats. Behav Brain Res 293:208–216

    Article  PubMed  Google Scholar 

  17. Branchi I, D’Andrea I, Sietzema J, Fiore M, Di Fausto V, Aloe L, Alleva E (2006) Early social enrichment augments adult hippocampal BDNF levels and survival of BrdU-positive cells while increasing anxiety- and “depression”-like behavior. J Neurosci Res 83(6):965–973

    Article  CAS  PubMed  Google Scholar 

  18. Bekinschtein P, Oomen CA, Saksida LM, Bussey TJ (2011) Effects of environmental enrichment and voluntary exercise on neurogenesis, learning and memory, and pattern separation: BDNF as a critical variable? Semin Cell Dev Biol 5:536–542

    Article  Google Scholar 

  19. Chourbaji S, Hörtnagl H, Molteni R, Riva MA, Gass P, Hellweg R (2012) The impact of environmental enrichment on sex-specific neurochemical circuitries—effects on brain-derived neurotrophic factor and the serotonergic system. Neuroscience 220:267–276

    Article  CAS  PubMed  Google Scholar 

  20. Perna JC, Wotjak CT, Stork O, Engelmann M (2015) Timing of presentation and nature of stimuli determine retroactive interference with social recognition memory in mice. Physiol Behav 143:10–14

    Article  CAS  PubMed  Google Scholar 

  21. Mak GK, Enwere EK, Gregg C, Pakarainen T, Poutanen M, Huhtaniemi I, Weiss S (2007) Male-pheromone-stimulated neurogenesis in the adult female brain: possible role in mating behavior. Nat Neurosci 10:1003–1011

    Article  CAS  PubMed  Google Scholar 

  22. Deng W, Gage FH (2015) The effect of immature adult-born dentate granule cells on hyponeophagial behavior is related to their roles in learning and memory. Front Syst Neurosci 9:1–12

    Google Scholar 

  23. Ming GL, Song H (2011) Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron 70(4):687–702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Dupret D, Fabre A, Döbrössy MD, Panatier A, Rodríguez JJ, Lamarque S, Lemaire V, Oliet SH et al (2007) Spatial learning depends on both the addition and removal of new hippocampal neurons. PLoS Biol 5(8):e214

    Article  PubMed  PubMed Central  Google Scholar 

  25. Tashiro A, Makino H, Gage FH (2007) Experience-specific functional modification of the dentate gyrus through adult neurogenesis: a critical period during an immature stage. J Neurosci 27(12):3252–3259

    Article  CAS  PubMed  Google Scholar 

  26. van Praag H, Schinder AF, Christie BR, Toni N, Palmer TD, Gage FH (2002) Functional neurogenesis in the adult hippocampus. Nature 415(6875):1030–1034

    Article  PubMed  Google Scholar 

  27. Schmidt-Hieber C, Jonas P, Bischofberger J (2004) Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus. Nature 429(6988):184–187

    Article  CAS  PubMed  Google Scholar 

  28. Gu Y, Arruda-Carvalho M, Wang J, Janoschka SR, Josselyn SA, Frankland PW, Ge S (2012) Optical controlling reveals time-dependent roles for adult-born dentate granule cells. Nat Neurosci 15(12):1700–1706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kuzumaki N, Ikegami D, Tamura R, Hareyama N, Imai S, Narita M, Torigoe K, Niikura K et al (2011) Hippocampal epigenetic modification at the brain-derived neurotrophic factor gene induced by an enriched environment. Hippocampus 21(2):127–132

    Article  CAS  PubMed  Google Scholar 

  30. Kesslak JP, So V, Choi J, Cotman CW, Gomez-Pinilla F (1998) Learning upregulates brain-derived neurotrophic factor messenger ribonucleic acid: a mechanism to facilitate encoding and circuit maintenance? Behav Neurosci 112(4):1012–1019

    Article  CAS  PubMed  Google Scholar 

  31. Breton-Provencher V, Lemasson M, Peralta MR 3rd, Saghatelyan A (2009) Interneurons produced in adulthood are required for the normal functioning of the olfactory bulb network and for the execution of selected olfactory behaviors. J Neurosci 29(48):15245–15257

    Article  CAS  PubMed  Google Scholar 

  32. Bekinschtein P, Cammarota M, Igaz LM, Bevilaqua LR, Izquierdo I, Medina JH (2007) Persistence of long-term memory storage requires a late protein synthesis- and BDNF-dependent phase in the hippocampus. Neuron 53(2):261–277

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

CAPES, FAPEMIG, and CNPq supported the present study. G.S.P was supported by a fellowship from CNPq.

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Correspondence to Grace Schenatto Pereira.

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The Animal Use Ethic Committee of the Universidade Federal de Minas Gerais (CEUA 44/2013) approved all the experimental procedures.

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Pereira-Caixeta, A.R., Guarnieri, L.O., Pena, R.R. et al. Neurogenesis Inhibition Prevents Enriched Environment to Prolong and Strengthen Social Recognition Memory, But Not to Increase BDNF Expression. Mol Neurobiol 54, 3309–3316 (2017). https://doi.org/10.1007/s12035-016-9922-2

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