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• W2942783247 abstract "In the adult mammalian hippocampus, new neurons arise from stem and progenitor cell division, in a process known as adult neurogenesis. Adult-generated neurons are sensitive to experience and may participate in hippocampal functions, including learning and memory, anxiety and stress regulation, and social behavior. Increasing evidence emphasizes the importance of new neuron connectivity within hippocampal circuitry for understanding the impact of adult neurogenesis on brain function. In this Review, we discuss how the functional consequences of new neurons arise from the collective interactions of presynaptic and postsynaptic neurons, glial cells, and the extracellular matrix, which together form the “tetrapartite synapse.” In the adult mammalian hippocampus, new neurons arise from stem and progenitor cell division, in a process known as adult neurogenesis. Adult-generated neurons are sensitive to experience and may participate in hippocampal functions, including learning and memory, anxiety and stress regulation, and social behavior. Increasing evidence emphasizes the importance of new neuron connectivity within hippocampal circuitry for understanding the impact of adult neurogenesis on brain function. In this Review, we discuss how the functional consequences of new neurons arise from the collective interactions of presynaptic and postsynaptic neurons, glial cells, and the extracellular matrix, which together form the “tetrapartite synapse.” It is now generally accepted that stem cells reside in the adult mammalian brain, and in certain regions, these cells divide in situ and give rise to new neurons, a phenomenon referred to as adult neurogenesis. In the hippocampus, adult neurogenesis produces one type of neuron—the dentate gyrus granule cell. The process begins with the largely asymmetric division of radial glial stem cells residing in the subgranular zone (sgz), a region just between the granule cell layer (gcl) and the hilus (Seri et al., 2001Seri B. García-Verdugo J.M. McEwen B.S. Alvarez-Buylla A. Astrocytes give rise to new neurons in the adult mammalian hippocampus.J. Neurosci. 2001; 21: 7153-7160Crossref PubMed Google Scholar). These cells have the capacity to self-renew and to generate either neurons or astrocytes (Bonaguidi et al., 2011Bonaguidi M.A. Wheeler M.A. Shapiro J.S. Stadel R.P. Sun G.J. Ming G.L. Song H. In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics.Cell. 2011; 145: 1142-1155Abstract Full Text Full Text PDF PubMed Scopus (433) Google Scholar, Suh et al., 2007Suh H. Consiglio A. Ray J. Sawai T. D’Amour K.A. Gage F.H. In vivo fate analysis reveals the multipotent and self-renewal capacities of Sox2+ neural stem cells in the adult hippocampus.Cell Stem Cell. 2007; 1: 515-528Abstract Full Text Full Text PDF PubMed Scopus (521) Google Scholar). The daughter cells of radial glial stem cells are highly proliferative amplifying stem cells, which in turn generate neuroblasts (Gonçalves et al., 2016aGonçalves J.T. Schafer S.T. Gage F.H. Adult neurogenesis in the hippocampus: from stem cells to behavior.Cell. 2016; 167: 897-914Abstract Full Text Full Text PDF PubMed Scopus (257) Google Scholar, Suh et al., 2007Suh H. Consiglio A. Ray J. Sawai T. D’Amour K.A. Gage F.H. In vivo fate analysis reveals the multipotent and self-renewal capacities of Sox2+ neural stem cells in the adult hippocampus.Cell Stem Cell. 2007; 1: 515-528Abstract Full Text Full Text PDF PubMed Scopus (521) Google Scholar) (Figure 1A). The cell bodies of these new neurons then migrate the short distance from the sgz into the gcl where they begin their differentiation into granule neurons (Gonçalves et al., 2016aGonçalves J.T. Schafer S.T. Gage F.H. Adult neurogenesis in the hippocampus: from stem cells to behavior.Cell. 2016; 167: 897-914Abstract Full Text Full Text PDF PubMed Scopus (257) Google Scholar) (Figure 1A). These new granule neurons then integrate into the circuitry of the hippocampus, where they subsequently impact behavioral function. In order to understand the functional consequences of adult neurogenesis, it is necessary to identify the circumstances that modulate the connectivity of newly generated neurons. The majority of research on this topic has focused exclusively on connectivity between neurons, without consideration of the influence of nonneuronal cells or the extracellular milieu in which new connections are formed. A growing literature suggests that understanding synaptic function and plasticity requires consideration of both glial cells as well as the extracellular matrix (ECM), which together with the presynaptic and postsynaptic neurons form the “tetrapartite synapse” (Dityatev and Rusakov, 2011Dityatev A. Rusakov D.A. Molecular signals of plasticity at the tetrapartite synapse.Curr. Opin. Neurobiol. 2011; 21: 353-359Crossref PubMed Scopus (121) Google Scholar, Smith et al., 2015aSmith A.C.W. Scofield M.D. Kalivas P.W. The tetrapartite synapse: Extracellular matrix remodeling contributes to corticoaccumbens plasticity underlying drug addiction.Brain Res. 2015; 1628: 29-39Crossref PubMed Scopus (27) Google Scholar). In this review, we consider the formation of new neurons from stem cells in the adult hippocampus, with specific relevance to the integration of new neurons into the circuitry and their impact on brain function. To review this material in a comprehensive and functionally meaningful way, we consider the production and integration of new neurons in the context of the tetrapartite synapse with specific reference to the influence of glia and the ECM on adult neurogenesis and hippocampal function. Although adult neurogenesis is robust in the hippocampus of rodents, the extent to which it exists in humans has been a matter of continued debate. Evidence that adult neurogenesis exists for a large number of species, ranging from rodents (Jessberger and Gage, 2014Jessberger S. Gage F.H. Adult neurogenesis: bridging the gap between mice and humans.Trends Cell Biol. 2014; 24: 558-563Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar, Snyder et al., 2009aSnyder J.S. Choe J.S. Clifford M.A. Jeurling S.I. Hurley P. Brown A. Kamhi J.F. Cameron H.A. Adult-born hippocampal neurons are more numerous, faster maturing, and more involved in behavior in rats than in mice.J. Neurosci. 2009; 29: 14484-14495Crossref PubMed Scopus (264) Google Scholar) to monkeys (Gould et al., 1998Gould E. Tanapat P. McEwen B.S. Flügge G. Fuchs E. Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress.Proc. Natl. Acad. Sci. USA. 1998; 95: 3168-3171Crossref PubMed Scopus (1055) Google Scholar, Gould et al., 1999Gould E. Reeves A.J. Fallah M. Tanapat P. Gross C.G. Fuchs E. Hippocampal neurogenesis in adult Old World primates.Proc. Natl. Acad. Sci. USA. 1999; 96: 5263-5267Crossref PubMed Scopus (572) Google Scholar), strongly suggests that this phenomenon is common to most mammalian species. In the rodent brain, the number of new neurons is substantial, with as many as 9,000 new granule cells being added to the young adult rat dentate gyrus daily (Cameron and McKay, 2001Cameron H.A. McKay R.D. Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus.J. Comp. Neurol. 2001; 435: 406-417Crossref PubMed Scopus (1178) Google Scholar). Relatively high numbers of new neurons have also been reported in the adult human hippocampus (Boldrini et al., 2018Boldrini M. Fulmore C.A. Tartt A.N. Simeon L.R. Pavlova I. Poposka V. Rosoklija G.B. Stankov A. Arango V. Dwork A.J. et al.Human hippocampal neurogenesis persists throughout aging.Cell Stem Cell. 2018; 22: 589-599Abstract Full Text Full Text PDF PubMed Scopus (206) Google Scholar, Eriksson et al., 1998Eriksson P.S. Perfilieva E. Björk-Eriksson T. Alborn A.M. Nordborg C. Peterson D.A. Gage F.H. Neurogenesis in the adult human hippocampus.Nat. Med. 1998; 4: 1313-1317Crossref PubMed Scopus (4373) Google Scholar, Knoth et al., 2010Knoth R. Singec I. Ditter M. Pantazis G. Capetian P. Meyer R.P. Horvat V. Volk B. Kempermann G. Murine features of neurogenesis in the human hippocampus across the lifespan from 0 to 100 years.PLoS ONE. 2010; 5: e8809Crossref PubMed Scopus (345) Google Scholar, Spalding et al., 2013Spalding K.L. Bergmann O. Alkass K. Bernard S. Salehpour M. Huttner H.B. Boström E. Westerlund I. Vial C. Buchholz B.A. et al.Dynamics of hippocampal neurogenesis in adult humans.Cell. 2013; 153: 1219-1227Abstract Full Text Full Text PDF PubMed Scopus (836) Google Scholar, Moreno-Jiménez et al., 2019Moreno-Jiménez E.P. Flor-García M. Terreros-Roncal J. Rábano A. Cafini F. Pallas-Bazarra N. Ávila J. Llorens-Martín M. Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer's disease.Nat. Med. 2019; 25: 554-560Crossref PubMed Scopus (4) Google Scholar). A few studies contradict these findings (Cipriani et al., 2018Cipriani S. Ferrer I. Aronica E. Kovacs G.G. Verney C. Nardelli J. Khung S. Delezoide A.L. Milenkovic I. Rasika S. et al.Hippocampal radial glial subtypes and their neurogenic potential in human fetuses and healthy and Alzheimer’s Disease adults.Cereb. Cortex. 2018; 28: 2458-2478Crossref PubMed Google Scholar, Sorrells et al., 2018Sorrells S.F. Paredes M.F. Cebrian-Silla A. Sandoval K. Qi D. Kelley K.W. James D. Mayer S. Chang J. Auguste K.I. et al.Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults.Nature. 2018; 555: 377-381Crossref PubMed Scopus (273) Google Scholar), but the majority of reports provide positive evidence for adult neurogenesis in the hippocampus of humans, suggesting that studying this process in rodents is likely relevant to understanding human brain plasticity. For this review, evidence from rodent studies will be considered except in cases otherwise stated. Once stem cell division produces immature neurons, these cells undergo an extensive maturation process that includes the growth of axons and dendrites and the formation of synaptic connections. Within 2 weeks of their generation, new neurons begin to take on the morphological characteristics of mature granule cells with a single dendritic tree extending toward the molecular layer and the formation of dendritic spines, primary sites of excitatory synapses (Zhao et al., 2006Zhao C. Teng E.M. Summers Jr., R.G. Ming G.L. Gage F.H. Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus.J. Neurosci. 2006; 26: 3-11Crossref PubMed Scopus (809) Google Scholar; Figure 1A). Beginning <1 week after their generation, new granule cells extend axons, known as mossy fibers, through the hilus toward the CA3 and CA2 subregions of the hippocampus (Llorens-Martín et al., 2015Llorens-Martín M. Jurado-Arjona J. Avila J. Hernández F. Novel connection between newborn granule neurons and the hippocampal CA2 field.Exp. Neurol. 2015; 263: 285-292Crossref PubMed Google Scholar, Zhao et al., 2006Zhao C. Teng E.M. Summers Jr., R.G. Ming G.L. Gage F.H. Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus.J. Neurosci. 2006; 26: 3-11Crossref PubMed Scopus (809) Google Scholar). Mossy fibers from new granule cells begin to form synapses with excitatory pyramidal cells in the CA3 and CA2 subregions (Gu et al., 2012Gu Y. Arruda-Carvalho M. Wang J. Janoschka S.R. Josselyn S.A. Frankland P.W. Ge S. Optical controlling reveals time-dependent roles for adult-born dentate granule cells.Nat. Neurosci. 2012; 15: 1700-1706Crossref PubMed Scopus (224) Google Scholar, Llorens-Martín et al., 2015Llorens-Martín M. Jurado-Arjona J. Avila J. Hernández F. Novel connection between newborn granule neurons and the hippocampal CA2 field.Exp. Neurol. 2015; 263: 285-292Crossref PubMed Google Scholar, Toni et al., 2008Toni N. Laplagne D.A. Zhao C. Lombardi G. Ribak C.E. Gage F.H. Schinder A.F. Neurons born in the adult dentate gyrus form functional synapses with target cells.Nat. Neurosci. 2008; 11: 901-907Crossref PubMed Scopus (489) Google Scholar) as well as with hilar mossy cells (Toni et al., 2008Toni N. Laplagne D.A. Zhao C. Lombardi G. Ribak C.E. Gage F.H. Schinder A.F. Neurons born in the adult dentate gyrus form functional synapses with target cells.Nat. Neurosci. 2008; 11: 901-907Crossref PubMed Scopus (489) Google Scholar) by ∼2–3 weeks post-mitosis (Figure 1B). Much research has focused on understanding how and when new granule cells integrate into the circuitry of the hippocampus. Mature granule cells are known to receive synaptic input from local GABAergic inhibitory interneurons, local and cortical glutamatergic inputs, and basal forebrain/midbrain/hindbrain neuromodulatory (cholinergic, dopaminergic, noradrenergic) nuclei (Deshpande et al., 2013Deshpande A. Bergami M. Ghanem A. Conzelmann K.K. Lepier A. Götz M. Berninger B. Retrograde monosynaptic tracing reveals the temporal evolution of inputs onto new neurons in the adult dentate gyrus and olfactory bulb.Proc. Natl. Acad. Sci. USA. 2013; 110: E1152-E1161Crossref PubMed Scopus (100) Google Scholar, Vivar et al., 2012Vivar C. Potter M.C. Choi J. Lee J.Y. Stringer T.P. Callaway E.M. Gage F.H. Suh H. van Praag H. Monosynaptic inputs to new neurons in the dentate gyrus.Nat. Commun. 2012; 3: 1107Crossref PubMed Scopus (153) Google Scholar). The formation of synapses onto new neurons is known to develop within a week or two of their generation, with the first inputs coming from local GABAergic inhibitory interneurons (Espósito et al., 2005Espósito M.S. Piatti V.C. Laplagne D.A. Morgenstern N.A. Ferrari C.C. Pitossi F.J. Schinder A.F. Neuronal differentiation in the adult hippocampus recapitulates embryonic development.J. Neurosci. 2005; 25: 10074-10086Crossref PubMed Scopus (464) Google Scholar, Ge et al., 2006Ge S. Goh E.L.K. Sailor K.A. Kitabatake Y. Ming G.L. Song H. GABA regulates synaptic integration of newly generated neurons in the adult brain.Nature. 2006; 439: 589-593Crossref PubMed Scopus (858) Google Scholar, Markwardt et al., 2009Markwardt S.J. Wadiche J.I. Overstreet-Wadiche L.S. Input-specific GABAergic signaling to newborn neurons in adult dentate gyrus.J. Neurosci. 2009; 29: 15063-15072Crossref PubMed Scopus (56) Google Scholar) followed by glutamatergic input from mossy cells in the hilus (Chancey et al., 2014Chancey J.H. Poulsen D.J. Wadiche J.I. Overstreet-Wadiche L. Hilar mossy cells provide the first glutamatergic synapses to adult-born dentate granule cells.J. Neurosci. 2014; 34: 2349-2354Crossref PubMed Scopus (52) Google Scholar) and then from the entorhinal cortex via the perforant path a few weeks later (Espósito et al., 2005Espósito M.S. Piatti V.C. Laplagne D.A. Morgenstern N.A. Ferrari C.C. Pitossi F.J. Schinder A.F. Neuronal differentiation in the adult hippocampus recapitulates embryonic development.J. Neurosci. 2005; 25: 10074-10086Crossref PubMed Scopus (464) Google Scholar, Ge et al., 2006Ge S. Goh E.L.K. Sailor K.A. Kitabatake Y. Ming G.L. Song H. GABA regulates synaptic integration of newly generated neurons in the adult brain.Nature. 2006; 439: 589-593Crossref PubMed Scopus (858) Google Scholar). Neuromodulatory input to adult-generated neurons occurs later (Deshpande et al., 2013Deshpande A. Bergami M. Ghanem A. Conzelmann K.K. Lepier A. Götz M. Berninger B. Retrograde monosynaptic tracing reveals the temporal evolution of inputs onto new neurons in the adult dentate gyrus and olfactory bulb.Proc. Natl. Acad. Sci. USA. 2013; 110: E1152-E1161Crossref PubMed Scopus (100) Google Scholar, Vivar et al., 2012Vivar C. Potter M.C. Choi J. Lee J.Y. Stringer T.P. Callaway E.M. Gage F.H. Suh H. van Praag H. Monosynaptic inputs to new neurons in the dentate gyrus.Nat. Commun. 2012; 3: 1107Crossref PubMed Scopus (153) Google Scholar), as does the formation of mature inhibitory inputs from local inhibitory interneurons (Espósito et al., 2005Espósito M.S. Piatti V.C. Laplagne D.A. Morgenstern N.A. Ferrari C.C. Pitossi F.J. Schinder A.F. Neuronal differentiation in the adult hippocampus recapitulates embryonic development.J. Neurosci. 2005; 25: 10074-10086Crossref PubMed Scopus (464) Google Scholar), all of which strongly resemble those of developmentally generated granule cells within 4–6 weeks post-mitosis (Laplagne et al., 2006Laplagne D.A. Espósito M.S. Piatti V.C. Morgenstern N.A. Zhao C. van Praag H. Gage F.H. Schinder A.F. Functional convergence of neurons generated in the developing and adult hippocampus.PLoS Biol. 2006; 4: e409Crossref PubMed Scopus (212) Google Scholar). On the output side, adult-generated granule cells form synapses with several populations of neurons within the hippocampus, including mossy cells in the hilus (Toni et al., 2008Toni N. Laplagne D.A. Zhao C. Lombardi G. Ribak C.E. Gage F.H. Schinder A.F. Neurons born in the adult dentate gyrus form functional synapses with target cells.Nat. Neurosci. 2008; 11: 901-907Crossref PubMed Scopus (489) Google Scholar), pyramidal cells of the CA2 and CA3 regions (Llorens-Martín et al., 2015Llorens-Martín M. Jurado-Arjona J. Avila J. Hernández F. Novel connection between newborn granule neurons and the hippocampal CA2 field.Exp. Neurol. 2015; 263: 285-292Crossref PubMed Google Scholar, Toni et al., 2008Toni N. Laplagne D.A. Zhao C. Lombardi G. Ribak C.E. Gage F.H. Schinder A.F. Neurons born in the adult dentate gyrus form functional synapses with target cells.Nat. Neurosci. 2008; 11: 901-907Crossref PubMed Scopus (489) Google Scholar), as well as inhibitory interneurons in the dentate gyrus itself and the CA3 region (Drew et al., 2016Drew L.J. Kheirbek M.A. Luna V.M. Denny C.A. Cloidt M.A. Wu M.V. Jain S. Scharfman H.E. Hen R. Activation of local inhibitory circuits in the dentate gyrus by adult-born neurons.Hippocampus. 2016; 26: 763-778Crossref PubMed Scopus (29) Google Scholar, Restivo et al., 2015Restivo L. Niibori Y. Mercaldo V. Josselyn S.A. Frankland P.W. Development of adult-generated cell connectivity with excitatory and inhibitory cell populations in the hippocampus.J. Neurosci. 2015; 35: 10600-10612Crossref PubMed Google Scholar; Figure 1B). One of the defining characteristics of a neuron is its ability to generate action potentials. Electrophysiological studies of new cells produced in the adult dentate gyrus have shown that this capability emerges relatively quickly (within a week) post-mitosis. For some time thereafter, new granule cells exhibit excitatory, instead of inhibitory, responses to the typically inhibitory neurotransmitter GABA (Chancey et al., 2013Chancey J.H. Adlaf E.W. Sapp M.C. Pugh P.C. Wadiche J.I. Overstreet-Wadiche L.S. GABA depolarization is required for experience-dependent synapse unsilencing in adult-born neurons.J. Neurosci. 2013; 33: 6614-6622Crossref PubMed Scopus (82) Google Scholar), suggesting that these cells are more likely to fire than mature granule cells, which are strongly inhibited (Amaral et al., 2007Amaral D.G. Scharfman H.E. Lavenex P. The dentate gyrus: fundamental neuroanatomical organization (dentate gyrus for dummies).Prog. Brain Res. 2007; 163: 3-22Crossref PubMed Scopus (324) Google Scholar, Pelkey et al., 2017Pelkey K.A. Chittajallu R. Craig M.T. Tricoire L. Wester J.C. McBain C.J. Hippocampal GABAergic inhibitory interneurons.Physiol. Rev. 2017; 97: 1619-1747Crossref PubMed Scopus (0) Google Scholar). Adult-generated granule neurons also display other unusual electrophysiological properties that disappear as they reach full maturity, including enhanced synaptic plasticity with a lower threshold for LTP induction (Ge et al., 2007Ge 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. 2007; 54: 559-566Abstract Full Text Full Text PDF PubMed Scopus (598) Google Scholar, Schmidt-Hieber et al., 2004Schmidt-Hieber C. Jonas P. Bischofberger J. Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus.Nature. 2004; 429: 184-187Crossref PubMed Scopus (858) Google Scholar). The heightened plasticity of adult-generated neurons makes them uniquely positioned to play a role in hippocampal-related functions, of which there are several candidates. Although the hippocampus was originally recognized for its role in certain types of learning and memory (reviewed in Eichenbaum, 2017Eichenbaum H. On the Integration of Space, Time, and Memory.Neuron. 2017; 95: 1007-1018Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar), it has also been found to play important roles in anxiety and stress regulation (reviewed in Fanselow and Dong, 2010Fanselow M.S. Dong H.W. Are the dorsal and ventral hippocampus functionally distinct structures?.Neuron. 2010; 65: 7-19Abstract Full Text Full Text PDF PubMed Scopus (1397) Google Scholar, Kheirbek et al., 2013Kheirbek M.A. Drew L.J. Burghardt N.S. Costantini D.O. Tannenholz L. Ahmari S.E. Zeng H. Fenton A.A. Hen R. Differential control of learning and anxiety along the dorsoventral axis of the dentate gyrus.Neuron. 2013; 77: 955-968Abstract Full Text Full Text PDF PubMed Scopus (274) Google Scholar), as well as in certain aspects of social behavior (reviewed in Opendak and Gould, 2015Opendak M. Gould E. Adult neurogenesis: a substrate for experience-dependent change.Trends Cogn. Sci. 2015; 19: 151-161Abstract Full Text Full Text PDF PubMed Google Scholar). Studies have shown that different parts of the hippocampus serve these different functions, with the dorsal hippocampus supporting spatial navigation learning and memory, and the ventral hippocampus as important for anxiety and stress regulation (reviewed in Fanselow and Dong, 2010Fanselow M.S. Dong H.W. Are the dorsal and ventral hippocampus functionally distinct structures?.Neuron. 2010; 65: 7-19Abstract Full Text Full Text PDF PubMed Scopus (1397) Google Scholar, Kheirbek et al., 2013Kheirbek M.A. Drew L.J. Burghardt N.S. Costantini D.O. Tannenholz L. Ahmari S.E. Zeng H. Fenton A.A. Hen R. Differential control of learning and anxiety along the dorsoventral axis of the dentate gyrus.Neuron. 2013; 77: 955-968Abstract Full Text Full Text PDF PubMed Scopus (274) Google Scholar). Because new neurons are generated throughout the dorsoventral extent of the dentate gyrus, the possibility that they might participate in more than one hippocampal function seems high. Indeed, adult-born neurons have been causally linked to many of the known functions and behaviors associated with the hippocampus. Much of this evidence comes from studies that knockdown or eliminate new neurons in the adult brain using transgenic, pharmacological, or focal x-irradiation approaches. Reports have shown that reduction of new neurons impairs cognitive performance on hippocampal-dependent tests, including object memory, contextual fear conditioning, as well as spatial learning and memory in the Morris water maze, Barnes maze, and radial arm maze (reviewed in Cameron and Glover, 2015Cameron H.A. Glover L.R. Adult neurogenesis: beyond learning and memory.Annu. Rev. Psychol. 2015; 66: 53-81Crossref PubMed Google Scholar, Gonçalves et al., 2016aGonçalves J.T. Schafer S.T. Gage F.H. Adult neurogenesis in the hippocampus: from stem cells to behavior.Cell. 2016; 167: 897-914Abstract Full Text Full Text PDF PubMed Scopus (257) Google Scholar; Figure 1C). On the other hand, contradictory studies have found either no effect of reduced neurogenesis on hippocampal cognitive tasks (Groves et al., 2013Groves J.O. Leslie I. Huang G.J. McHugh S.B. Taylor A. Mott R. Munafò M. Bannerman D.M. Flint J. Ablating adult neurogenesis in the rat has no effect on spatial processing: evidence from a novel pharmacogenetic model.PLoS Genet. 2013; 9: e1003718Crossref PubMed Scopus (61) Google Scholar, Saxe et al., 2006Saxe M.D. Battaglia F. Wang J.W. Malleret G. David D.J. Monckton J.E. Garcia A.D. Sofroniew M.V. Kandel E.R. Santarelli L. et al.Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus.Proc. Natl. Acad. Sci. USA. 2006; 103: 17501-17506Crossref PubMed Scopus (718) Google Scholar) or only on certain types of hippocampal cognitive tests (Shors et al., 2002Shors 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. 2002; 12: 578-584Crossref PubMed Scopus (648) Google Scholar). One study even found that the absence of new neurons improves cognitive function (Saxe et al., 2007Saxe M.D. Malleret G. Vronskaya S. Mendez I. Garcia A.D. Sofroniew M.V. Kandel E.R. Hen R. Paradoxical influence of hippocampal neurogenesis on working memory.Proc. Natl. Acad. Sci. USA. 2007; 104: 4642-4646Crossref PubMed Scopus (0) Google Scholar). New neurons, presumably through their unique electrophysiological properties and sparse connections to CA3 neurons (Amaral et al., 2007Amaral D.G. Scharfman H.E. Lavenex P. The dentate gyrus: fundamental neuroanatomical organization (dentate gyrus for dummies).Prog. Brain Res. 2007; 163: 3-22Crossref PubMed Scopus (324) Google Scholar), have also been found to participate in pattern separation (Clelland et al., 2009Clelland C.D. Choi M. Romberg C. Clemenson Jr., G.D. Fragniere A. Tyers P. Jessberger S. Saksida L.M. Barker R.A. Gage F.H. Bussey T.J. A functional role for adult hippocampal neurogenesis in spatial pattern separation.Science. 2009; 325: 210-213Crossref PubMed Scopus (917) Google Scholar, Danielson et al., 2016Danielson N.B. Kaifosh P. Zaremba J.D. Lovett-Barron M. Tsai J. Denny C.A. Balough E.M. Goldberg A.R. Drew L.J. Hen R. et al.Distinct contribution of adult-born hippocampal granule cells to context encoding.Neuron. 2016; 90: 101-112Abstract Full Text Full Text PDF PubMed Google Scholar, Sahay et al., 2011Sahay A. Scobie K.N. Hill A.S. O’Carroll C.M. Kheirbek M.A. Burghardt N.S. Fenton A.A. Dranovsky A. Hen R. Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation.Nature. 2011; 472: 466-470Crossref PubMed Scopus (818) Google Scholar), the process of making similar neural inputs distinct. Elimination or optogenetic silencing of adult-born neurons impairs pattern separation-like behaviors (Clelland et al., 2009Clelland C.D. Choi M. Romberg C. Clemenson Jr., G.D. Fragniere A. Tyers P. Jessberger S. Saksida L.M. Barker R.A. Gage F.H. Bussey T.J. A functional role for adult hippocampal neurogenesis in spatial pattern separation.Science. 2009; 325: 210-213Crossref PubMed Scopus (917) Google Scholar, Danielson et al., 2016Danielson N.B. Kaifosh P. Zaremba J.D. Lovett-Barron M. Tsai J. Denny C.A. Balough E.M. Goldberg A.R. Drew L.J. Hen R. et al.Distinct contribution of adult-born hippocampal granule cells to context encoding.Neuron. 2016; 90: 101-112Abstract Full Text Full Text PDF PubMed Google Scholar), while transgenic increases in adult neurogenesis enhance the ability of mice to distinguish between highly similar contexts (Sahay et al., 2011Sahay A. Scobie K.N. Hill A.S. O’Carroll C.M. Kheirbek M.A. Burghardt N.S. Fenton A.A. Dranovsky A. Hen R. Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation.Nature. 2011; 472: 466-470Crossref PubMed Scopus (818) Google Scholar). One study, however, reported that pattern separation-like behaviors did not differ between transgenic rats with reduced neurogenesis and controls with typical new neuron numbers (Groves et al., 2013Groves J.O. Leslie I. Huang G.J. McHugh S.B. Taylor A. Mott R. Munafò M. Bannerman D.M. Flint J. Ablating adult neurogenesis in the rat has no effect on spatial processing: evidence from a novel pharmacogenetic model.PLoS Genet. 2013; 9: e1003718Crossref PubMed Scopus (61) Google Scholar). While reports from direct manipulations of adult neurogenesis often lack consistent results, the majority of studies suggest that new neurons are involved in some aspect of hippocampal-related cognition. Reduced numbers of new neurons have also been associated with excessive anxiety (Revest et al., 2009Revest J.M. Dupret D. Koehl M. Funk-Reiter C. Grosjean N. Piazza P.V. Abrous D.N. Adult hippocampal neurogenesis is involved in anxiety-related behaviors.Mol. Psychiatry. 2009; 14: 959-967Crossref PubMed Scopus (278) Google Scholar), but most studies suggest that the role of new neurons in anxiety regulation only comes into play under conditions of stress (Figure 1C). Adult neurogenesis in the hippocampus seems to provide resilience to stress-induced anxiety (Anacker et al., 2018Anacker C. Luna V.M. Stevens G.S. Millette A. Shores R. Jimenez J.C. Chen B. Hen R. Hippocampal neurogenesis confers stress resilience by inhibiting the ventral dentate gyrus.Nature. 2018; 559: 98-102Crossref PubMed Scopus (3) Google Scholar, Hill et al., 2015Hill A.S. Sahay A. Hen R. Increasing adult hippocampal neurogenesis is sufficient to reduce anxiety and depression-like behaviors.Neuropsychopharmacology. 2015; 40: 2368-2378Crossref PubMed Scopus (143) Google Scholar, Snyder et al., 2011Snyder J.S. Soumier A. Brewer M. Pickel J. Cameron H.A. Adult hippocampal neurogenesis buffers stress responses and depressive behaviour.Nature. 2011; 476: 458-461Crossref PubMed Scopus (723) Google Scholar). Studies have also shown impairments in social behavior tests in rodents lacking new neurons. Adult neurogenesis in the hippocampus has been shown to be necessary for stress-induced social avoidance (Lagace et al., 2010Lagace D.C. Donovan M.H. DeCarolis N.A. Farnbauch L.A. Malhotra S. Berton O. Nestler E.J. Krishnan V. Eisch A.J. Adult hippocampal neurogenesis is functionally important for stress-induced social avoidance.Proc. Natl. Acad. Sci. USA. 2010; 107: 4436-4441Crossref PubMed Scopus (157) Google Scholar), as well as in social recognition memory (Garrett et al., 2015Garrett L. Zhang J. Zimprich A. Niedermeier K.M. Fuchs H. Gail" @default.
• W2942783247 created "2019-05-09" @default.
• W2942783247 creator A5011488411 @default.
• W2942783247 creator A5075579627 @default.
• W2942783247 date "2019-05-01" @default.
• W2942783247 modified "2023-10-16" @default.
• W2942783247 title "Adult Neurogenesis, Glia, and the Extracellular Matrix" @default.
• W2942783247 cites W1509390099 @default.
• W2942783247 cites W1510674622 @default.
• W2942783247 cites W1533790491 @default.
• W2942783247 cites W1542136448 @default.
• W2942783247 cites W1543985160 @default.
• W2942783247 cites W1601934261 @default.
• W2942783247 cites W1642619469 @default.
• W2942783247 cites W1883162734 @default.
• W2942783247 cites W1906305879 @default.
• W2942783247 cites W1964173716 @default.
• W2942783247 cites W1966506721 @default.
• W2942783247 cites W1967321689 @default.
• W2942783247 cites W1967913887 @default.
• W2942783247 cites W1968903290 @default.
• W2942783247 cites W1975285965 @default.
• W2942783247 cites W1976582013 @default.
• W2942783247 cites W1980457368 @default.
• W2942783247 cites W1980789245 @default.
• W2942783247 cites W1981571957 @default.
• W2942783247 cites W1982528484 @default.
• W2942783247 cites W1985033427 @default.
• W2942783247 cites W1987375164 @default.
• W2942783247 cites W1988766176 @default.
• W2942783247 cites W1989897544 @default.
• W2942783247 cites W1990864995 @default.
• W2942783247 cites W1997864984 @default.
• W2942783247 cites W2000381670 @default.
• W2942783247 cites W2002112050 @default.
• W2942783247 cites W2002161951 @default.
• W2942783247 cites W2003041124 @default.
• W2942783247 cites W2004229492 @default.
• W2942783247 cites W2010598641 @default.
• W2942783247 cites W2011230199 @default.
• W2942783247 cites W2011580597 @default.
• W2942783247 cites W2011670043 @default.
• W2942783247 cites W2012438895 @default.
• W2942783247 cites W2014099101 @default.
• W2942783247 cites W2014140314 @default.
• W2942783247 cites W2016500868 @default.
• W2942783247 cites W2018743597 @default.
• W2942783247 cites W2022585706 @default.
• W2942783247 cites W2022932966 @default.
• W2942783247 cites W2022944768 @default.
• W2942783247 cites W2023343492 @default.
• W2942783247 cites W2025604203 @default.
• W2942783247 cites W2026082008 @default.
• W2942783247 cites W2026147918 @default.
• W2942783247 cites W2026154459 @default.
• W2942783247 cites W2026928443 @default.
• W2942783247 cites W2028620081 @default.
• W2942783247 cites W2028938479 @default.
• W2942783247 cites W2029819292 @default.
• W2942783247 cites W2031482209 @default.
• W2942783247 cites W2033617297 @default.
• W2942783247 cites W2035557202 @default.
• W2942783247 cites W2039808373 @default.
• W2942783247 cites W2039954704 @default.
• W2942783247 cites W2040502575 @default.
• W2942783247 cites W2040692117 @default.
• W2942783247 cites W2040901919 @default.
• W2942783247 cites W2045247162 @default.
• W2942783247 cites W2045485656 @default.
• W2942783247 cites W2050015055 @default.
• W2942783247 cites W2051005796 @default.
• W2942783247 cites W2051173215 @default.
• W2942783247 cites W2051359369 @default.
• W2942783247 cites W2052724410 @default.
• W2942783247 cites W2053256857 @default.
• W2942783247 cites W2054459050 @default.
• W2942783247 cites W2054505706 @default.
• W2942783247 cites W2055823139 @default.
• W2942783247 cites W2057386575 @default.
• W2942783247 cites W2058696184 @default.
• W2942783247 cites W2061497228 @default.
• W2942783247 cites W2063466545 @default.
• W2942783247 cites W2064424963 @default.
• W2942783247 cites W2065527300 @default.
• W2942783247 cites W2066943555 @default.
• W2942783247 cites W2067128446 @default.
• W2942783247 cites W2067856703 @default.
• W2942783247 cites W2068677218 @default.
• W2942783247 cites W2068999504 @default.
• W2942783247 cites W2069281265 @default.
• W2942783247 cites W2069374541 @default.
• W2942783247 cites W2069866488 @default.
• W2942783247 cites W2072733897 @default.
• W2942783247 cites W2073196527 @default.
• W2942783247 cites W2074764259 @default.
• W2942783247 cites W2078070194 @default.
• W2942783247 cites W2078181370 @default.
• W2942783247 cites W2079156156 @default.

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