Adult Neurogenesis

Throughout adulthood new neurons are continuously added to the dentate gyrus, a hippocampal sub-region that plays a critical role in spatial learning. These new neurons are generated in the subgranular zone (SGZ). From there, they migrate into the granule cell layer (GCL), and begin to extend axons toward CA3 and dendrites toward the molecular layer (ML). In the mouse, several thousand new neurons are generated each day, and the rate of proliferation is influenced by a large number of external factors including neurotransmitters, hormones, growth factors as well as environmental factors. By 2 weeks of age axon has extended into CA3 and dendritic processes have extended into the outer edge of the ML. Soon after, at around 2.5 weeks, spines begin to develop, and as theses new neurons start to receive excitatory input from perforant path. Between 4 and 8 weeks there is continued growth of dendritic processes, spinogenesis, and, in addition, at this point new neurons have lower threshold for LTP, LTD and are more excitable. Our lab is interested in how these new neurons contribute to hippocampal memory function. In particular we are interested in how new neurons regulate clearance of memories from the hippocampus (or forgetting).

 

Publications on this topic:

  1. Guskjolen, A., Josselyn, S.A. and Frankland, P.W. (2017). Age-dependent changes in spatial memory retention and flexibility in mice. Neurobiology of Learning and Memory, in press.

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  2. Yang, G., Cancino, G.I., Zahr, S., Guskjolen, A., Voronova, A., Gallagher, D., Frankland, P.W., Kaplan, D.R. and Miller, F.D. (2016). A Glo1-methylglyoxal pathway that is perturbed in maternal diabetes regulates embryonic and adult neural stem cell pools in offspring. Cell Reports, 17, 1022-1036.

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  3. Gouveia, A., Hsu, K., Niibori, Y., Seegobin, M., Cancino, G.I., He, L., Wondisford, F.E., Bennett, S., Lagace, D., Frankland, P.W., Wang, J. (2016). The aPKC-CBP pathway regulates adult hippocampal neurogenesis in an age-dependent manner. Stem Cell Reports, 7, 719-734.

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  4. Epp, J.R. and Frankland, P.W. (2016). Re-engineering the hippocampus. Neuron, 91, 1190-91.

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  5. Ishikawa, R., Fukushima, H., Frankland, P.W. and Kida, S. (2016). Hippocampal neurogenesis enhancers promote forgetting of remote fear memory after hippocampal reactivation by retrieval. eLife, 5. pii: e17464.

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  6. Epp, J.R., Silva Mera, R., Köhler, S., Josselyn, S.A. and Frankland, P.W. (2016). Neurogenesis-mediated forgetting minimizes proactive interference. Nature Communications, 7:10838. doi: 10.1038/ncomms10838

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  7. Frankland and Josselyn (2016). Hippocampal neurogenesis and m emory clearance. Neuropsychoparmacology, 41, 382-383.

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  8. Restivo, L., Niibori, Y., Mercaldo, V., Josselyn, S.A. and Frankland, P.W. (2015). Development of adult-generated cell connectivity with excitatory and inhibitory cell populations in the hippocampus. Journal of Neuroscience, 35, 10600-12

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  9. Arruda-Carvalho, M., Akers, K.G., Guskjolen, A., Sakaguchi, M., Josselyn, S.A. and Frankland, P.W. (2014). Post-training ablation of adult-generated olfactory granule cells degrades odor-reward memories. Journal of Neuroscience, 34, 15793-803.

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  10. Arruda-Carvalho, M., Restivo, L., Epp, J.R., Elgersma, Y., Josselyn, S.A. and Frankland, P.W. (2014). Conditional deletion of α-CaMKII impairs integration of adult-generated granule cells into dentate gyrus circuits and hippocampus-dependent learning. Journal of Neuroscience, 34, 11919-28.

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  11. Akers, K.G.*, Martinez-Canabal, A.*, Restivo, L.*, Yiu, A.P., de Cristofaro, A., Hsiang, H-L., Wheeler, A.L., Guskjolen, A., Niibori, Y., Shoji, H., Ohira, K., Richards, B.A., Miyakawa, T., Josselyn, S.A. and Frankland, P.W. (2014). Hippocampal neurogenesis regulates forgetting during adulthood and infancy. Science, 344, 598-602. *equal contribution

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  12. Frankland, P.W., Kohler, S. and Josselyn, S.A. (2013). Hippocampal neurogenesis and forgetting. Trends in Neuroscience, 36, 497-503.

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  13. Frankland, P.W. (2013). Neurogenic evangelism: Comment on Urbach et al. Behavioral Neuroscience, 127, 126-129.

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  14. Martinez-Canabal, A., Wheeler, A.L., Sarkis, D., Lu, W.-Y., Buckwalter, M.S., Lerch, J.P., Wyss-Coray, T., Josselyn, S.A. and Frankland, P.W. (2013). Chronic over-expression of TGFβ1 alters hippocampal structure and causes spatial learning deficits. Hippocampus, 23, 1198-1211. doi: 10.1002/hipo.22159

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  15. Cancino, G.I., Yiu, A.P., Fatt, M., Dugani, C., Flores, E., Frankland, P.W., Josselyn, S.A., Kaplan, D.R. and Miller, F.D. (2013). p63 regulates adult neural precursor and newly-born neuron survival to control hippocampal-dependent behavior. Journal of Neuroscience, 33, 12569-85.

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  16. Niibori, Y., Yu, T.-S., Epp, J.R., Akers, K.G., Josselyn, S.A. and Frankland, P.W. (2012). Suppression of adult neurogenesis impairs population coding of similar contexts in the hippocampal CA3 region. Nature Communications, 3, 1253.

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  17. Akers, K.G., Arruda-Carvalho, M., Josselyn, S.A., and Frankland, P.W. (2012). The ontogeny of fear memory formation, specificity and persistence in mice. Learning & Memory, 19, 598-604.

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  18. Gu, Y., Arruda-Carvalho, M., Wang, J., Janoschka, S., Josselyn, S.A., Frankland, P.W.+ and Ge, S.+ (2012). Reversible silencing of adult-born granule cells blocks hippocampal-dependent memory retrieval. Nature Neuroscience, 15, 1700-6. doi:10.1038/nn.3260. +co-corresponding authors

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  19. Josselyn, S.A. and Frankland, P.W. (2012). Infantile amnesia: A neurogenic hypothesis. Learning & Memory, 19, 423-433.

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  20. Wang, J.*, Gallagher, D.*, DeVito, L.M, Cancino, G.I., Tsui, D., Keller, G.M., Frankland, P.W., Kaplan, D.R. and Miller, F.D. (2012). Metformin activates atypical PKCs to promote rodent and human neurogenesis and enhances hippocampus-dependent learning. Cell Stem Cell, 11, 23-35. *equal contribution

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  21. Martinez-Canabal, A.*, Akers, K.G.*, Josselyn, S.A. and Frankland, P.W. (2013). The effect of suppressing hippocampal neurogenesis on spatial learning changes across the lifespan. Hippocampus, 23, 66-74.

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  22. Arruda-Carvalho, M.*, Sakaguchi, M.*, Akers, K.G., Josselyn, S.A. and Frankland, P.W. (2011). Posttraining ablation of adult-generated neurons degrades previously acquired memories. Journal of Neuroscience, 31, 15113-27. *equal contribution

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  23. Stone, S.S.D., Teixeira, C.M., DeVito, L., Zaslavsky, K., Josselyn, S.A., Lozano, A.M. and Frankland, P.W. (2011). Stimulation of entorhinal cortex promotes adult neurogenesis and facilitates spatial memory. Journal of Neuroscience, 31, 13469-84.

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  24. Sakaguchi, M., Arruda-Carvalho, M., Imaizumi, Y., Kang, N.H., Poirier, F., Okano, H. and Frankland, P.W. (2011). Impaired spatial and contextual memory formation in galectin-1 deficient mice. Molecular Brain, 4: 33.

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  25. Leslie, A.T.*, Akers, K.G.*, Krakowski, A., Stone, S.S.D., Arruda-Carvalho, M., Sakaguchi, M. and Frankland, P.W. (2011). Impact of early adverse experience on complexity of adult-generated neurons. Translational Psychiatry, 1, e35; doi:10.1038/tp.2011.38. *equal contribution

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  26. Akers, K.G., Kushner, S.A., Leslie, A.T., Clarke, L., van der Kooy, D., Lerch, J. and Frankland, P.W. (2011). Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice. Molecular Brain, 4: 29.

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  27. Lerch, J.P., Yiu, A.P., Martinez-Canabal, A., Pekar, T., Bohbot, V., Frankland, P.W., Henkelman, R.M., Josselyn, S.A., Sled, J.G. (2011). Maze training in mice induces MRI detectable brain shape changes specific to the type of learning. Neuroimage, 54, 2086-95.

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  28. Stone, S.S.D., Teixeira, C.M., Zaslavsky, K.., Wheeler, A.L., Martinez-Canabal A., Wang, A.H., Sakaguchi, M., Lozano, A.M. and Frankland, P.W. (2011). Functional convergence of developmentally- and adult-generated granule cells in dentate gyrus circuits supporting hippocampus-dependent memory. Hippocampus [Epub ahead of print].

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  29. Akers, K.G., Sakaguchi, M., Arruda-Carvalho, M. (2010). Functional Contribution of Adult-Generated Olfactory Bulb Interneurons: Odor Discrimination versus Odor Memory. Journal of Neuroscience 30(13):4523-4525

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  30. Frankland, P.W. and Miller, F.D. (2008). Regenerating your senses: multiple roles for neurogenesis in the adult brain. Nature Neuroscience, 11, 1124-1126

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  31. Kee, N.*, Teixeira, C.M.*, Wang, A.H.* and Frankland, P.W. (2007). Imaging activation of adult-generated granule cells in spatial memory. Nature Protocols, 12, 3033-3044. *equal contribution

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  32. Kee, N.*, Teixeira, C.M.*, Wang, A.H. and Frankland, P.W. (2007). Preferential incorporation of adult-generated granule cells into spatial memory networks in the dentate gyrus. Nature Neuroscience, 10, 355-362. *equal contribution

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