Taupin, P. & Gage, F. H. Adult neurogenesis and neural stem cells of the central nervous system in mammals. J. Neurosci. Res. 69, 745–749 (2002).
Spalding, K. L. et al. Dynamics of hippocampal neurogenesis in adult humans. Cell 153, 1219–1227 (2013).
This important study provided evidence for continued neurogenesis in adulthood at rates that suggest that it may have an important role in human behaviour.
Kjelstrup, K. B. et al. Finite scale of spatial representation in the hippocampus. Science 321, 140–143 (2008).
Thompson, C. L. et al. Genomic anatomy of the hippocampus. Neuron 60, 1010–1021 (2008).
Fanselow, M. S. & Dong, H. W. Are the dorsal and ventral hippocampus functionally distinct structures? Neuron 65, 7–19 (2010).
Strange, B. A., Witter, M. P., Lein, E. S. & Moser, E. I. Functional organization of the hippocampal longitudinal axis. Nat. Rev. Neurosci. 15, 655–669 (2014).
Kheirbek, M. A. et al. Differential control of learning and anxiety along the dorsoventral axis of the dentate gyrus. Neuron 77, 955–968 (2013).
This study showed that mature granule neurons in the dorsal dentate gyrus are important for learning, whereas granule neurons in the ventral dentate gyrus control anxiety.
Maguire, E. A. et al. Navigation-related structural change in the hippocampi of taxi drivers. Proc. Natl Acad. Sci. USA 97, 4398–4403 (2000).
Colombo, M., Fernandez, T., Nakamura, K. & Gross, C. G. Functional differentiation along the anterior–posterior axis of the hippocampus in monkeys. J. Neurophysiol. 80, 1002–1005 (1998).
Felix-Ortiz, A. C. & Tye, K. M. Amygdala inputs to the ventral hippocampus bidirectionally modulate social behavior. J. Neurosci. 34, 586–595 (2014).
Hughes, K. R. Dorsal and ventral hippocampus lesions and maze learning: influence of preoperative environment. Can. J. Psychol. 19, 325–332 (1965).
Stevens, R. & Cowey, A. Effects of dorsal and ventral hippocampal lesions on spontaneous alternation, learned alternation and probability learning in rats. Brain Res. 52, 203–224 (1973).
Henke, P. G. Hippocampal pathway to the amygdala and stress ulcer development. Brain Res. Bull. 25, 691–695 (1990).
Moser, E., Moser, M. B. & Andersen, P. Spatial learning impairment parallels the magnitude of dorsal hippocampal lesions, but is hardly present following ventral lesions. J. Neurosci. 13, 3916–3925 (1993).
Boldrini, M. et al. Benzodiazepines and the potential trophic effect of antidepressants on dentate gyrus cells in mood disorders. Int. J. Neuropsychopharmacol. 17, 1923–1933 (2014).
Shackman, A. J. et al. Neural mechanisms underlying heterogeneity in the presentation of anxious temperament. Proc. Natl Acad. Sci. USA 110, 6145–6150 (2013).
O'Leary, O. F. & Cryan, J. F. A ventral view on antidepressant action: roles for adult hippocampal neurogenesis along the dorsoventral axis. Trends Pharmacol. Sci. 35, 675–687 (2014).
Jinno, S. Topographic differences in adult neurogenesis in the mouse hippocampus: a stereology-based study using endogenous markers. Hippocampus 21, 467–480 (2011).
Snyder, J. S., Radik, R., Wojtowicz, J. M. & Cameron, H. A. Anatomical gradients of adult neurogenesis and activity: young neurons in the ventral dentate gyrus are activated by water maze training. Hippocampus 19, 360–370 (2009).
Tanti, A. et al. Region-dependent and stage-specific effects of stress, environmental enrichment, and antidepressant treatment on hippocampal neurogenesis. Hippocampus 23, 797–811 (2013).
Piatti, V. C. et al. The timing for neuronal maturation in the adult hippocampus is modulated by local network activity. J. Neurosci. 31, 7715–7728 (2011).
Tanti, A., Rainer, Q., Minier, F., Surget, A. & Belzung, C. Differential environmental regulation of neurogenesis along the septo-temporal axis of the hippocampus. Neuropharmacology. 63, 374–384 (2012).
Kempermann, G., Kuhn, H. G. & Gage, F. H. More hippocampal neurons in adult mice living in an enriched environment. Nature 386, 493–495 (1997).
Lehmann, M. L., Brachman, R. A., Martinowich, K., Schloesser, R. J. & Herkenham, M. Glucocorticoids orchestrate divergent effects on mood through adult neurogenesis. J. Neurosci. 33, 2961–2972 (2013).
Wu, M. V. & Hen, R. Functional dissociation of adult-born neurons along the dorsoventral axis of the dentate gyrus. Hippocampus 24, 751–761 (2014).
Boldrini, M. et al. Antidepressants increase neural progenitor cells in the human hippocampus. Neuropsychopharmacology 34, 2376–2389 (2009).
Christensen, T., Bisgaard, C. F., Nielsen, H. B. & Wiborg, O. Transcriptome differentiation along the dorso–ventral axis in laser-captured microdissected rat hippocampal granular cell layer. Neuroscience 170, 731–741 (2010).
Adhikari, A., Topiwala, M. A. & Gordon, J. A. Synchronized activity between the ventral hippocampus and the medial prefrontal cortex during anxiety. Neuron 65, 257–269 (2010).
Padilla-Coreano, N. et al. Direct ventral hippocampal–prefrontal input is required for anxiety-related neural activity and behavior. Neuron 89, 857–866 (2016).
Richardson, M. P., Strange, B. A. & Dolan, R. J. Encoding of emotional memories depends on amygdala and hippocampus and their interactions. Nat. Neurosci. 7, 278–285 (2004).
Britt, J. P. et al. Synaptic and behavioral profile of multiple glutamatergic inputs to the nucleus accumbens. Neuron 76, 790–803 (2012).
Bagot, R. C. et al. Ventral hippocampal afferents to the nucleus accumbens regulate susceptibility to depression. Nat. Commun. 6, 7062 (2015).
Anacker, C. Adult hippocampal neurogenesis in depression: behavioral implications and regulation by the stress system. Curr. Top. Behav. Neurosci. 18, 25–43 (2014).
Anacker, C., Zunszain, P. A., Carvalho, L. A. & Pariante, C. M. The glucocorticoid receptor: pivot of depression and of antidepressant treatment? Psychoneuroendocrinology 36, 415–425 (2011).
Anacker, C. et al. Neuroanatomic differences associated with stress susceptibility and resilience. Biol. Psychiatry 79, 840–849 (2016).
Tannenholz, L., Hen, R. & Kheirbek, M. A. GluN2B-containing NMDA receptors on adult-born granule cells contribute to the antidepressant action of fluoxetine. Front. Neurosci. 10, 242 (2016).
Danielson, N. B. et al. Distinct contribution of adult-born hippocampal granule cells to context encoding. Neuron 90, 101–112 (2016).
Cameron, H. A. & McKay, R. D. Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus. J. Comp. Neurol. 435, 406–417 (2001).
Ge, S., Yang, C. H., Hsu, K. S., Ming, G. L. & Song, H. A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain. Neuron 54, 559–566 (2007).
Toni, N. & Schinder, A. F. Maturation and functional integration of new granule cells into the adult hippocampus. Cold Spring Harb. Perspect. Biol. 8, a018903 (2016).
Denny, C. A., Burghardt, N. S., Schachter, D. M., Hen, R. & Drew, M. R. 4- to 6-week-old adult-born hippocampal neurons influence novelty-evoked exploration and contextual fear conditioning. Hippocampus 22, 1188–1201 (2012).
Gould, E., Beylin, A., Tanapat, P., Reeves, A. & Shors, T. J. Learning enhances adult neurogenesis in the hippocampal formation. Nat. Neurosci. 2, 260–265 (1999).
This study showed that adult-born neurons are affected by associative memory formation.
Shors, T. J. et al. Neurogenesis in the adult is involved in the formation of trace memories. Nature 410, 372–376 (2001).
Shors, T. J., Townsend, D. A., Zhao, M., Kozorovitskiy, Y. & Gould, E. Neurogenesis may relate to some but not all types of hippocampal-dependent learning. Hippocampus 12, 578–584 (2002).
Leuner, B. et al. Learning enhances the survival of new neurons beyond the time when the hippocampus is required for memory. J. Neurosci. 24, 7477–7481 (2004).
Drapeau, E. et al. Spatial memory performances of aged rats in the water maze predict levels of hippocampal neurogenesis. Proc. Natl Acad. Sci. USA 100, 14385–14390 (2003).
Ambrogini, P. et al. Learning may reduce neurogenesis in adult rat dentate gyrus. Neurosci. Lett. 359, 13–16 (2004).
Döbrössy, M. D. et al. Differential effects of learning on neurogenesis: learning increases or decreases the number of newly born cells depending on their birth date. Mol. Psychiatry 8, 974–982 (2003).
Winocur, G., Wojtowicz, J. M., Sekeres, M., Snyder, J. S. & Wang, S. Inhibition of neurogenesis interferes with hippocampus-dependent memory function. Hippocampus 16, 296–304 (2006).
Dupret, D. et al. Spatial learning depends on both the addition and removal of new hippocampal neurons. PLoS Biol. 5, e214 (2007).
Kesner, R. P. et al. The role of postnatal neurogenesis in supporting remote memory and spatial metric processing. Hippocampus 24, 1663–1671 (2014).
Kempermann, G., Kuhn, H. G. & Gage, F. H. Experience-induced neurogenesis in the senescent dentate gyrus. J. Neurosci. 18, 3206–3212 (1998).
van Praag, H., Kempermann, G. & Gage, F. H. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat. Neurosci. 2, 266–270 (1999).
Tashiro, A., Sandler, V. M., Toni, N., Zhao, C. & Gage, F. H. NMDA-receptor-mediated, cell-specific integration of new neurons in adult dentate gyrus. Nature 442, 929–933 (2006).
Kirby, E. D. et al. Basolateral amygdala regulation of adult hippocampal neurogenesis and fear-related activation of newborn neurons. Mol. Psychiatry 17, 527–536 (2012).
Schoenfeld, T. J., Rada, P., Pieruzzini, P. R., Hsueh, B. & Gould, E. Physical exercise prevents stress-induced activation of granule neurons and enhances local inhibitory mechanisms in the dentate gyrus. J. Neurosci. 33, 7770–7777 (2013).
Stone, S. S. et al. Stimulation of entorhinal cortex promotes adult neurogenesis and facilitates spatial memory. J. Neurosci. 31, 13469–13484 (2011).
Kee, N., Teixeira, C. M., Wang, A. H. & Frankland, P. W. Preferential incorporation of adult-generated granule cells into spatial memory networks in the dentate gyrus. Nat. Neurosci. 10, 355–362 (2007).
Aimone, J. B., Wiles, J. & Gage, F. H. Potential role for adult neurogenesis in the encoding of time in new memories. Nat. Neurosci. 9, 723–727 (2006).
Rangel, L. M. et al. Temporally selective contextual encoding in the dentate gyrus of the hippocampus. Nat. Commun. 5, 3181 (2014).
Tashiro, A., Makino, H. & Gage, F. H. Experience-specific functional modification of the dentate gyrus through adult neurogenesis: a critical period during an immature stage. J. Neurosci. 27, 3252–3259 (2007).
Stone, S. S. et al. Functional convergence of developmentally and adult-generated granule cells in dentate gyrus circuits supporting hippocampus-dependent memory. Hippocampus 21, 1348–1362 (2011).
Aimone, J. B., Wiles, J. & Gage, F. H. Computational influence of adult neurogenesis on memory encoding. Neuron 61, 187–202 (2009).
Appleby, P. A. & Wiskott, L. Additive neurogenesis as a strategy for avoiding interference in a sparsely-coding dentate gyrus. Network 20, 137–161 (2009).
Appleby, P. A., Kempermann, G. & Wiskott, L. The role of additive neurogenesis and synaptic plasticity in a hippocampal memory model with grid-cell like input. PLoS Comput. Biol. 7, e1001063 (2011).
Lacefield, C. O., Itskov, V., Reardon, T., Hen, R. & Gordon, J. A. Effects of adult-generated granule cells on coordinated network activity in the dentate gyrus. Hippocampus 22, 106–116 (2012).
Burghardt, N. S., Park, E. H., Hen, R. & Fenton, A. A. Adult-born hippocampal neurons promote cognitive flexibility in mice. Hippocampus 22, 1795–1808 (2012).
Ikrar, T. et al. Adult neurogenesis modifies excitability of the dentate gyrus. Front. Neural Circuits 7, 204 (2013).
Drew, L. J. et al. Activation of local inhibitory circuits in the dentate gyrus by adult-born neurons. Hippocampus 26, 763–778 (2016).
Temprana, S. G. et al. Delayed coupling to feedback inhibition during a critical period for the integration of adult-born granule cells. Neuron 85, 116–130 (2015).
Karst, H. & Joëls, M. Effect of chronic stress on synaptic currents in rat hippocampal dentate gyrus neurons. J. Neurophysiol. 89, 625–633 (2003).
McGaugh, J. L. et al. Neuromodulatory systems and memory storage: role of the amygdala. Behav. Brain Res. 58, 81–90 (1993).
Marr, D. Simple memory: a theory for archicortex. Phil. Trans. R. Soc. Lond. B 262, 23–81 (1971).
Becker, S. A computational principle for hippocampal learning and neurogenesis. Hippocampus 15, 722–738 (2005).
Leutgeb, J. K., Leutgeb, S., Moser, M. B. & Moser, E. I. Pattern separation in the dentate gyrus and CA3 of the hippocampus. Science 315, 961–966 (2007).
This was the first in vivo electrophysiology study to show that signals from the entorhinal cortex can be decorrelated both by the dentate gyrus and by the recruitment of nonoverlapping cell assemblies in CA3.
McHugh, T. J. et al. Dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal network. Science 317, 94–99 (2007).
Clelland, C. D. et al. A functional role for adult hippocampal neurogenesis in spatial pattern separation. Science 325, 210–213 (2009).
This was the first study to show that neurogenesis is necessary for behavioural pattern separation.
Wiskott, L., Rasch, M. J. & Kempermann, G. A functional hypothesis for adult hippocampal neurogenesis: avoidance of catastrophic interference in the dentate gyrus. Hippocampus 16, 329–343 (2006).
Kheirbek, M. A., Klemenhagen, K. C., Sahay, A. & Hen, R. Neurogenesis and generalization: a new approach to stratify and treat anxiety disorders. Nat. Neurosci. 15, 1613–1620 (2012).
Neunuebel, J. P., Yoganarasimha, D., Rao, G. & Knierim, J. J. Conflicts between local and global spatial frameworks dissociate neural representations of the lateral and medial entorhinal cortex. J. Neurosci. 33, 9246–9258 (2013).
Tronel, S. et al. Adult-born neurons are necessary for extended contextual discrimination. Hippocampus 22, 292–298 (2012).
Creer, D. J., Romberg, C., Saksida, L. M., van Praag, H. & Bussey, T. J. Running enhances spatial pattern separation in mice. Proc. Natl Acad. Sci. USA 107, 2367–2372 (2010).
Coba, M. P. et al. TNiK is required for postsynaptic and nuclear signaling pathways and cognitive function. J. Neurosci. 32, 13987–13999 (2012).
Sahay, A. et al. Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature 472, 466–470 (2011).
This study developed the first mouse model to specifically increase neurogenesis and showed that mice with increased neurogenesis have an improved pattern separation ability.
Kent, B. A. et al. The orexigenic hormone acyl-ghrelin increases adult hippocampal neurogenesis and enhances pattern separation. Psychoneuroendocrinology 51, 431–439 (2015).
Bekinschtein, P. et al. Brain-derived neurotrophic factor interacts with adult-born immature cells in the dentate gyrus during consolidation of overlapping memories. Hippocampus 24, 905–911 (2014).
Bekinschtein, P. et al. BDNF in the dentate gyrus is required for consolidation of “pattern-separated” memories. Cell Rep. 5, 759–768 (2013).
McAvoy, K. M. et al. Modulating neuronal competition dynamics in the dentate gyrus to rejuvenate aging memory circuits. Neuron 91, 1356–1373 (2016).
Nakashiba, T. et al. Young dentate granule cells mediate pattern separation, whereas old granule cells facilitate pattern completion. Cell 149, 188–201 (2012).
O'Reilly, R. C. & McClelland, J. L. Hippocampal conjunctive encoding, storage, and recall: avoiding a trade-off. Hippocampus 4, 661–682 (1994).
Jung, M. W. & McNaughton, B. L. Spatial selectivity of unit activity in the hippocampal granular layer. Hippocampus 3, 165–182 (1993).
McAvoy, K., Besnard, A. & Sahay, A. Adult hippocampal neurogenesis and pattern separation in DG: a role for feedback inhibition in modulating sparseness to govern population-based coding. Front. Syst. Neurosci. 9, 120 (2015).
Deng, W., Aimone, J. B. & Gage, F. H. New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat. Rev. Neurosci. 11, 339–350 (2010).
Denny, C. A. et al. Hippocampal memory traces are differentially modulated by experience, time, and adult neurogenesis. Neuron 83, 189–201 (2014).
Tayler, K. K., Tanaka, K. Z., Reijmers, L. G. & Wiltgen, B. J. Reactivation of neural ensembles during the retrieval of recent and remote memory. Curr. Biol. 23, 99–106 (2013).
Ramirez, S. et al. Creating a false memory in the hippocampus. Science 341, 387–391 (2013).
This study generated an artificial fear memory and was able to induce fearful behaviour by activating this memory.
Redondo, R. L. et al. Bidirectional switch of the valence associated with a hippocampal contextual memory engram. Nature 513, 426–430 (2014).
Ramirez, F., Moscarello, J. M., LeDoux, J. E. & Sears, R. M. Active avoidance requires a serial basal amygdala to nucleus accumbens shell circuit. J. Neurosci. 35, 3470–3477 (2015).
Kitamura, T. et al. Adult neurogenesis modulates the hippocampus-dependent period of associative fear memory. Cell 139, 814–827 (2009).
Akers, K. G. et al. Hippocampal neurogenesis regulates forgetting during adulthood and infancy. Science 344, 598–602 (2014).
Epp, J. R., Silva Mera, R., Köhler, S., Josselyn, S. A. & Frankland, P. W. Neurogenesis-mediated forgetting minimizes proactive interference. Nat. Commun. 7, 10838 (2016).
This study showed that neurogenesis minimizes proactive memory interference, which could be important for cognitive flexibility.
Monk, C. S. et al. Human hippocampal activation in the delayed matching- and nonmatching-to-sample memory tasks: an event-related functional MRI approach. Behav. Neurosci. 116, 716–721 (2002).
Takahashi, H. et al. Differential contributions of prefrontal and hippocampal dopamine D1 and D2 receptors in human cognitive functions. J. Neurosci. 28, 12032–12038 (2008).
Park, E. H., Burghardt, N. S., Dvorak, D., Hen, R. & Fenton, A. A. Experience-dependent regulation of dentate gyrus excitability by adult-born granule cells. J. Neurosci. 35, 11656–11666 (2015).
Dupret, D. et al. Spatial relational memory requires hippocampal adult neurogenesis. PLoS ONE 3, e1959 (2008).
Garthe, A., Behr, J. & Kempermann, G. Adult-generated hippocampal neurons allow the flexible use of spatially precise learning strategies. PLoS ONE 4, e5464 (2009).
Swan, A. A. et al. Characterization of the role of adult neurogenesis in touch-screen discrimination learning. Hippocampus 24, 1581–1591 (2014).
Rubin, R. D., Watson, P. D., Duff, M. C. & Cohen, N. J. The role of the hippocampus in flexible cognition and social behavior. Front. Hum. Neurosci. 8, 742 (2014).
McClelland, J. L., McNaughton, B. L., O'Reilly, R. C. Why there are complementary learning systems in the hippocampus and neocortex: insights from the successes and failures of connectionist models of learning and memory. Psychol. Rev. 102, 419–457 (1995).
Hvoslef-Eide, M. & Oomen, C. A. Adult neurogenesis and pattern separation in rodents: a critical evaluation of data, tasks and interpretation. Front. Biol. 11, 168–181 (2016).
Garthe, A., Roeder, I. & Kempermann, G. Mice in an enriched environment learn more flexibly because of adult hippocampal neurogenesis. Hippocampus 26, 261–271 (2016).
Kalm, M., Karlsson, N., Nilsson, M. K. & Blomgren, K. Loss of hippocampal neurogenesis, increased novelty-induced activity, decreased home cage activity, and impaired reversal learning one year after irradiation of the young mouse brain. Exp. Neurol. 247, 402–409 (2013).
Garthe, A., Huang, Z., Kaczmarek, L., Filipkowski, R. K. & Kempermann, G. Not all water mazes are created equal: cyclin D2 knockout mice with constitutively suppressed adult hippocampal neurogenesis do show specific spatial learning deficits. Genes Brain Behav. 13, 357–364 (2014).
Lucassen, P. J. et al. Regulation of adult neurogenesis and plasticity by (early) stress, glucocorticoids, and inflammation. Cold Spring Harb. Perspect. Biol. 7, a021303 (2015).
Santarelli, L. et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 301, 805–809 (2003).
This was the first study to show that neurogenesis is necessary for some of the behavioural effects of antidepressants.
Surget, A. et al. Antidepressants recruit new neurons to improve stress response regulation. Mol. Psychiatry 16, 1177–1188 (2011).
Surget, A. et al. Drug-dependent requirement of hippocampal neurogenesis in a model of depression and of antidepressant reversal. Biol. Psychiatry 64, 293–301 (2008).
Ramirez, S. et al. Activating positive memory engrams suppresses depression-like behaviour. Nature 522, 335–339 (2015).
The authors of this study were able to induce antidepressant-like behavioural effects by artificially activating memory engrams of positive events.
Coe, C. L. et al. Prenatal stress diminishes neurogenesis in the dentate gyrus of juvenile rhesus monkeys. Biol. Psychiatry 54, 1025–1034 (2003).
Lemaire, V., Koehl, M., Le Moal, M. & Abrous, D. N. Prenatal stress produces learning deficits associated with an inhibition of neurogenesis in the hippocampus. Proc. Natl Acad. Sci. USA 97, 11032–11037 (2000).
Mirescu, C., Peters, J. D. & Gould, E. Early life experience alters response of adult neurogenesis to stress. Nat. Neurosci. 7, 841–846 (2004).
Perera, T. D. et al. Necessity of hippocampal neurogenesis for the therapeutic action of antidepressants in adult nonhuman primates. PLoS ONE 6, e17600 (2011).
Perera, T. D. et al. Antidepressant-induced neurogenesis in the hippocampus of adult nonhuman primates. J. Neurosci. 27, 4894–4901 (2007).
Wu, M. V. et al. Impact of social status and antidepressant treatment on neurogenesis in the baboon hippocampus. Neuropsychopharmacology 39, 1861–1871 (2014).
Lucassen, P. J., Stumpel, M. W., Wang, Q. & Aronica, E. Decreased numbers of progenitor cells but no response to antidepressant drugs in the hippocampus of elderly depressed patients. Neuropharmacology 58, 940–949 (2010).
Bessa, J. M. et al. The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling. Mol. Psychiatry 14, 764–773 (2009).
David, D. J. et al. Neurogenesis-dependent and -independent effects of fluoxetine in an animal model of anxiety/depression. Neuron 62, 479–493 (2009).
Hill, A. S., Sahay, A. & Hen, R. Increasing adult hippocampal neurogenesis is sufficient to reduce anxiety and depression-like behaviors. Neuropsychopharmacology 40, 2368–2378 (2015).
Revest, J. M. et al. Adult hippocampal neurogenesis is involved in anxiety-related behaviors. Mol. Psychiatry 14, 959–967 (2009).
Murray, F., Smith, D. W. & Hutson, P. H. Chronic low dose corticosterone exposure decreased hippocampal cell proliferation, volume and induced anxiety and depression like behaviours in mice. Eur. J. Pharmacol. 583, 115–127 (2008).
Oomen, C. A., Mayer, J. L., de Kloet, E. R., Joels, M. & Lucassen, P. J. Brief treatment with the glucocorticoid receptor antagonist mifepristone normalizes the reduction in neurogenesis after chronic stress. Eur. J. Neurosci. 26, 3395–3401 (2007).
Mayer, J. L. et al. Brief treatment with the glucocorticoid receptor antagonist mifepristone normalises the corticosterone-induced reduction of adult hippocampal neurogenesis. J. Neuroendocrinol. 18, 629–631 (2006).
Anacker, C. et al. Role for the kinase SGK1 in stress, depression, and glucocorticoid effects on hippocampal neurogenesis. Proc. Natl Acad. Sci. USA 110, 8708–8713 (2013).
Anacker, C. A. et al. Glucocorticoid-related molecular signaling pathways regulating hippocampal neurogenesis. Neuropsychopharmacology 38, 872–883 (2013).
Schloesser, R. J., Manji, H. K. & Martinowich, K. Suppression of adult neurogenesis leads to an increased hypothalamo–pituitary–adrenal axis response. Neuroreport 20, 553–557 (2009).
Snyder, J. S., Soumier, A., Brewer, M., Pickel, J. & Cameron, H. A. Adult hippocampal neurogenesis buffers stress responses and depressive behaviour. Nature 476, 458–461 (2011).
This was the first study to demonstrate that mice with complete ablation of neurogenesis show elevated glucocorticoid responses and anxiety-like and depressive-like behaviour in response to acute moderate stress.
Mateus-Pinheiro, A. et al. Sustained remission from depressive-like behavior depends on hippocampal neurogenesis. Transl Psychiatry 3, e210 (2013).
Deng, W., Saxe, M. D., Gallina, I. S. & Gage, F. H. Adult-born hippocampal dentate granule cells undergoing maturation modulate learning and memory in the brain. J. Neurosci. 29, 13532–13542 (2009).
Keith, J., Velezmoro, R., O'Brien, C. Correlates of cognitive flexibility in veterans seeking treatment for posttraumatic stress disorder. J. Nerv. Ment. Dis. 203, 287–293 (2015).
Chamberlain, S. R. et al. Impaired cognitive flexibility and motor inhibition in unaffected first-degree relatives of patients with obsessive-compulsive disorder. Am. J. Psychiatry 164, 335–338 (2007).
Deveney, C. M. & Deldin, P. J. A preliminary investigation of cognitive flexibility for emotional information in major depressive disorder and non-psychiatric controls. Emotion 6, 429–437 (2006).
Malberg, J. E., Eisch, A. J., Nestler, E. J. & Duman, R. S. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J. Neurosci. 20, 9104–9110 (2000).
This was the first study to show that different antidepressant treatments increase adult hippocampal neurogenesis.
Banasr, M., Soumier, A., Hery, M., Mocaer, E. & Daszuta, A. Agomelatine, a new antidepressant, induces regional changes in hippocampal neurogenesis. Biol. Psychiatry 59, 1087–1096 (2006).
Dagyte, G. et al. The novel antidepressant agomelatine normalizes hippocampal neuronal activity and promotes neurogenesis in chronically stressed rats. CNS Neurosci. Ther. 16, 195–207 (2010).
Boldrini, M. et al. Hippocampal angiogenesis and progenitor cell proliferation are increased with antidepressant use in major depression. Biol. Psychiatry 72, 562–571 (2012).
Anacker, C. et al. Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor. Mol. Psychiatry 16, 738–750 (2011).
Lee, J., Duan, W. & Mattson, M. P. Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice. J. Neurochem. 82, 1367–1375 (2002).
Stangl, D. & Thuret, S. Impact of diet on adult hippocampal neurogenesis. Genes Nutr. 4, 271–282 (2009).
Walker, A. K. et al. The P7C3 class of neuroprotective compounds exerts antidepressant efficacy in mice by increasing hippocampal neurogenesis. Mol. Psychiatry 20, 500–508 (2015).
Shors, T. J., Olson, R. L., Bates, M. E., Selby, E. A. & Alderman, B. L. Mental and physical (MAP) training: a neurogenesis-inspired intervention that enhances health in humans. Neurobiol. Learn. Mem. 115, 3–9 (2014).
Craft, L. L. & Perna, F. M. The benefits of exercise for the clinically depressed. Prim. Care Companion J. Clin. Psychiatry 6, 104–111 (2004).
Meshi, D. et al. Hippocampal neurogenesis is not required for behavioral effects of environmental enrichment. Nat. Neurosci. 9, 729–731 (2006).
Scharfman, H. E. Functional implications of seizure-induced neurogenesis. Adv. Exp. Med. Biol. 548, 192–212 (2004).
Scharfman, H. E. & Hen, R. Neuroscience. Is more neurogenesis always better? Science 315, 336–338 (2007).
Jin, K. et al. Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo. Proc. Natl Acad. Sci. USA 99, 11946–11950 (2002).
Li, Y. et al. TrkB regulates hippocampal neurogenesis and governs sensitivity to antidepressive treatment. Neuron 59, 399–412 (2008).
Conboy, L. et al. Macrophage migration inhibitory factor is critically involved in basal and fluoxetine-stimulated adult hippocampal cell proliferation and in anxiety, depression, and memory-related behaviors. Mol. Psychiatry 16, 533–547 (2011).
Samuels, B. A. et al. 5-HT1A receptors on mature dentate gyrus granule cells are critical for the antidepressant response. Nat. Neurosci. 18, 1606–1616 (2015).
This study emphasized for the first time the role of mature granule neurons in the dentate gyrus as crucial mediators of the antidepressant response.
Madroñal, N. et al. Rapid erasure of hippocampal memory following inhibition of dentate gyrus granule cells. Nat. Commun. 7, 10923 (2016).
Dalley, R. A., Ng, L. L. & Guillozet-Bongaarts, A. L. Dentate gyrus (DG). Allen Brain Atlas Community Site http://community.brain-map.org/download/attachments/798/DG.pdf?version=1 (2017).
Hasler, G., Drevets, W. C., Manji, H. K. & Charney, D. S. Discovering endophenotypes for major depression. Neuropsychopharmacology 29, 1765–1781 (2004).
Cuthbert, B. N. & Insel, T. R. Toward the future of psychiatric diagnosis: the seven pillars of RDoC. BMC Med. 11, 126 (2013).
Donaldson, Z. R. & Hen, R. From psychiatric disorders to animal models: a bidirectional and dimensional approach. Biol. Psychiatry 77, 15–21 (2014).
Manganas, L. N. et al. Magnetic resonance spectroscopy identifies neural progenitor cells in the live human brain. Science 318, 980–985 (2007).
Rueger, M. A. et al. Noninvasive imaging of endogenous neural stem cell mobilization in vivo using positron emission tomography. J. Neurosci. 30, 6454–6460 (2010).
Tamura, Y. et al. Noninvasive evaluation of cellular proliferative activity in brain neurogenic regions in rats under depression and treatment by enhanced [18F]FLT-PET imaging. J. Neurosci. 36, 8123–8131 (2016).
Pereira, A. C. et al. An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc. Natl Acad. Sci. USA 104, 5638–5643 (2007).
Yu, D. X. et al. Modeling hippocampal neurogenesis using human pluripotent stem cells. Stem Cell Rep. 2, 295–310 (2014).
Fatehullah, A., Tan, S. H. & Barker, N. Organoids as an in vitro model of human development and disease. Nat. Cell Biol. 18, 246–254 (2016).
Lacy, J. W., Yassa, M. A., Stark, S. M., Muftuler, L. T. & Stark, C. E. Distinct pattern separation related transfer functions in human CA3/dentate and CA1 revealed using high-resolution fMRI and variable mnemonic similarity. Learn. Mem. 18, 15–18 (2011).
Bakker, A., Kirwan, C. B., Miller, M. & Stark, C. E. Pattern separation in the human hippocampal CA3 and dentate gyrus. Science 319, 1640–1642 (2008).
This fMRI study provided the first evidence for a role of the dentate gyrus–CA3 in pattern separation in humans.
Leal, S. L., Tighe, S. K., Jones, C. K. & Yassa, M. A. Pattern separation of emotional information in hippocampal dentate and CA3. Hippocampus 24, 1146–1155 (2014).
Becker, S., Macqueen, G. & Wojtowicz, J. M. Computational modeling and empirical studies of hippocampal neurogenesis-dependent memory: effects of interference, stress and depression. Brain Res. 1299, 45–54 (2009).
Miller, J. F. et al. Neural activity in human hippocampal formation reveals the spatial context of retrieved memories. Science 342, 1111–1114 (2013).
Déry, N., Goldstein, A. & Becker, S. A role for adult hippocampal neurogenesis at multiple time scales: a study of recent and remote memory in humans. Behav. Neurosci. 129, 435–449 (2015).
Déry, N. et al. Adult hippocampal neurogenesis reduces memory interference in humans: opposing effects of aerobic exercise and depression. Front. Neurosci. 7, 66 (2013).
Gould, N. F. et al. Performance on a virtual reality spatial memory navigation task in depressed patients. Am. J. Psychiatry 164, 516–519 (2007).
Channon, S. Executive dysfunction in depression: the Wisconsin Card Sorting Test. J. Affect. Disord. 39, 107–114 (1996).
Degl'Innocenti, A., Agren, H. & Bäckman, L. Executive deficits in major depression. Acta Psychiatr. Scand. 97, 182–188 (1998).
Corcoran, R. & Upton, D. A role for the hippocampus in card sorting? Cortex 29, 293–304 (1993).
McAlonan, K. & Brown, V. J. Orbital prefrontal cortex mediates reversal learning and not attentional set shifting in the rat. Behav. Brain Res. 146, 97–103 (2003).
Brown, V. J. & Tait, D. S. Attentional set-shifting across species. Curr. Top. Behav. Neurosci. 28, 363–395 (2016).
Marsh, R. et al. Reward-based spatial learning in unmedicated adults with obsessive–compulsive disorder. Am. J. Psychiatry 172, 383–392 (2015).
Cole, S. W., Yoo, D. J. & Knutson, B. Interactivity and reward-related neural activation during a serious videogame. PLoS ONE 7, e33909 (2012).
Mishra, J., Anguera, J. A. & Gazzaley, A. Video games for neuro-cognitive optimization. Neuron 90, 214–218 (2016).
Pikkarainen, M., Rönkkö, S., Savander, V., Insausti, R. & Pitkänen, A. Projections from the lateral, basal, and accessory basal nuclei of the amygdala to the hippocampal formation in rat. J. Comp. Neurol. 403, 229–260 (1999).
Felix-Ortiz, A. C. et al. BLA to vHPC inputs modulate anxiety-related behaviors. Neuron 79, 658–664 (2013).
Bazelot, M. et al. Hippocampal theta input to the amygdala shapes feedforward inhibition to gate heterosynaptic plasticity. Neuron 87, 1290–1303 (2015).
Watanabe, Y., Gould, E. & McEwen, B. S. Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons. Brain Res. 588, 341–345 (1992).