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Adult Neurogenesis, Glia, and the Extracellular Matrix
Open accessAbstract
In the adult mammalian hippocampus, new neurons arise from stem and progenitor cell division, a process known as adult neurogenesis. Adult-generated neurons are sensitive to experience and may participate in hippocampal functions, including cognition, anxiety/stress regulation, and social behavior. Increasing evidence emphasizes the importance of new neuron connectivity within the 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”.
Overview
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Written from the paper’s full text.
TL;DR
This review argues that adult hippocampal neurogenesis and its functional effects depend on new neuron connectivity within the “tetrapartite synapse,” comprising pre- and postsynaptic neurons, glia, and extracellular matrix. It synthesizes rodent evidence showing that experience and pathology alter new neuron production, integration, and behavior, with glia and ECM as key regulators.
Key findings
- Adult hippocampal neurogenesis produces dentate gyrus granule cells; as many as 9,000 new granule cells are added daily to the young adult rat dentate gyrus. New neurons receive GABAergic inputs first, then glutamatergic input from hilar mossy cells, then entorhinal cortical input, and strongly resemble developmentally generated granule cells by 4–6 weeks post-mitosis.
- Adult-born neurons have been linked to hippocampal cognition, anxiety/stress regulation, social behavior, and pattern separation, but direct manipulations often yield inconsistent results; some studies find no effect of reduced neurogenesis, effects only on certain cognitive tests, or even improved cognitive function after ablation.
- More new neurons are not always beneficial: stroke, seizure, and blunt trauma increase adult neurogenesis yet are associated with reduced cognitive function; inhibiting neurogenesis reduces chronic seizures and seizure-related cognitive decline as well as stroke-induced cognitive decline. Fluoxetine-induced overproduction of new neurons was associated with cognitive decline, increased susceptibility to stress-induced depression, and excessive anxiety.
- Rewarding experiences such as voluntary exercise, environmental enrichment, and sexual experience enhance adult neurogenesis and hippocampal function, whereas aversive stress, aging, and parenting suppress it. Glia and ECM components—including chondroitin sulfate proteoglycans, reelin, MMP9, tenascin-R, and perineuronal nets—regulate new neuron number, migration, dendritic maturation, synapse formation/elimination, and plasticity; ECM is noted to compose approximately 20% of brain volume.
Methods
- Narrative review; no primary experimental data or sample. It synthesizes published rodent studies except where otherwise stated.
- Focuses on adult hippocampal neurogenesis and the tetrapartite synapse, citing evidence on stem/progenitor division, new neuron integration, behavior, glia, ECM, and perineuronal nets; includes Table 1 and Figures 1–4.
- Main analysis is qualitative synthesis of cited literature; no systematic review, meta-analysis, or new statistical analysis is reported.
Limitations
- Stated: the extent of adult neurogenesis in humans remains debated, with some studies contradicting positive findings; direct manipulations of adult neurogenesis often produce inconsistent behavioral results.
- Stated gaps: several areas are relatively uninvestigated, including how enriched environment alters axon connections of adult-generated neurons, effects of sexual experience on stem cells and connectivity, PNNs in adult neurogenesis, MMPs in intact adult neurogenesis, and the extent to which glia influence functional connectivity of new neurons.
- Evident: as a narrative review relying largely on rodent studies, it cannot establish causality or quantify effect sizes; conclusions depend on the selection and interpretation of cited literature.
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Claims the paper makes
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In the paper
“Beginning less than 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., 2015; Zhao et al., 2006).”
§ Adult neurogenesis, glia, and the extracellular matrix > Evidence of adult neurogenesis and the integration of new neurons into the hippocampal circuitry
What the sources say
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Electrophysiological studies of new cells produced in the adult dentate gyrus have shown that this capability emerges relatively quickly (within a week) post-mitosis.”
§ Adult neurogenesis, glia, and the extracellular matrix > Function of adult-generated neurons
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“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., 2006) (Figure 1A).”
§ Adult neurogenesis, glia, and the extracellular matrix > Evidence of adult neurogenesis and the integration of new neurons into the hippocampal circuitry
What the sources say
- Not checked yetcites Zhao et al., 2006 source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Relatively high numbers of new neurons have also been reported in the adult human hippocampus (Boldrini et al., 2018; Eriksson et al., 1998; Knoth et al., 2010; Spalding et al., 2013).”
§ Adult neurogenesis, glia, and the extracellular matrix > Evidence of adult neurogenesis and the integration of new neurons into the hippocampal circuitry
What the sources say
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Mossy fibers from new granule cells begin to form synapses with excitatory pyramidal cells in the CA3 and CA2 subregions (Gu et al., 2012; Llorens-Martín et al., 2015; Toni et al., 2008) as well as with hilar mossy cells (Toni et al., 2008) by approximately 2–3 weeks post-mitosis (Figure 1B).”
§ Adult neurogenesis, glia, and the extracellular matrix > Evidence of adult neurogenesis and the integration of new neurons into the hippocampal circuitry
What the sources say
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“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., 2007; Schmidt-Hieber et al., 2004).”
§ Adult neurogenesis, glia, and the extracellular matrix > Function of adult-generated neurons
What the sources say
- Not checked yetcites Ge et al., 2007
- Not checked yetcites Schmidt-Hieber et al., 2004 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“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, 2001).”
§ Adult neurogenesis, glia, and the extracellular matrix > Evidence of adult neurogenesis and the integration of new neurons into the hippocampal circuitry
What the sources say
- Not checked yetcites Cameron and McKay, 2001
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“In the adult mammalian hippocampus, new neurons arise from stem and progenitor cell division, a process known as adult neurogenesis.”
§ Adult neurogenesis, glia, and the extracellular matrix > Abstract
What the sources say
- Not checked yetcites Seri et al., 2001 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The heightened plasticity of adult-generated neurons make them uniquely positioned to play a role in hippocampal-related functions, of which there are many candidates.”
§ Adult neurogenesis, glia, and the extracellular matrix > Function of adult-generated neurons
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Furthermore, new neurons, presumably through their unique electrophysiological properties and sparse connections to CA3 neurons (Amaral et al., 2007), have been found to participate in pattern separation (Clelland et al., 2009; Danielson et al., 2016; Sahay et al., 2011), the process of making similar neural inputs distinct.”
§ Adult neurogenesis, glia, and the extracellular matrix > Function of adult-generated neurons
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Manipulations used to reduce adult neurogenesis (transgenic, pharmacological, or focal x-irradiation approaches) affect hippocampal function specifically through loss of new neurons rather than through off-target effects.
- It may state two separate claims as one. 46
- Probably not a substantial claim. 10
None of the sources cited for this claim have been checked yet.
In the paper
“For some time thereafter, new granule cells exhibit excitatory instead of inhibitory responses to typically inhibitory neurotransmitter GABA (Chancey et al., 2013), suggesting that these cells are more likely to fire than mature granule cells, which are strongly inhibited (Amaral et al., 2007; Pelkey et al., 2017).”
§ Adult neurogenesis, glia, and the extracellular matrix > Function of adult-generated neurons
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In the hippocampus, adult neurogenesis produces one type of neuron – the dentate gyrus granule cell.”
§ Adult neurogenesis, glia, and the extracellular matrix > Introduction
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Evidence that adult neurogenesis exists for a large number of species, ranging from rodents (Jessberger and Gage, 2014; Snyder et al., 2009a) to monkeys (Gould et al., 1998, 1999), strongly suggests that this phenomenon is common to most mammalian species.”
§ Adult neurogenesis, glia, and the extracellular matrix > Evidence of adult neurogenesis and the integration of new neurons into the hippocampal circuitry
What the sources say
- Not checked yetcites Jessberger and Gage, 2014 source
- Not matchedcites Snyder et al., 2009a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Gould et al., 1998, 1999
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“A few studies contradict these findings (Cipriani et al., 2018; Sorrells et al., 2018), 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.”
§ Adult neurogenesis, glia, and the extracellular matrix > Evidence of adult neurogenesis and the integration of new neurons into the hippocampal circuitry
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Pharmacological blockade of adult neurogenesis rescued the deleterious behavioral effects induced by antidepressant treatment strongly suggesting that in this case, the new neurons impaired hippocampal function (Alves et al., 2017).”
§ Adult neurogenesis, glia, and the extracellular matrix > Paradoxical effects of adult neurogenesis on hippocampal function
What the sources say
- Not checked yetcites Alves et al., 2017 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Manipulations used to reduce adult neurogenesis (transgenic, pharmacological, or focal x-irradiation approaches) affect hippocampal function specifically through loss of new neurons rather than through off-target effects.
None of the sources cited for this claim have been checked yet.
In the paper
“Stress seems to inhibit adult neurogenesis by having a suppressive action on the proliferation of radial stem cells and amplifying progenitors, leading to a reduction in neuroblasts (Dagytė et al., 2009; Mirescu et al., 2004; Opendak et al., 2016) (Table 1).”
§ Adult neurogenesis, glia, and the extracellular matrix > Aversive experiences alter adult neurogenesis
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“On the other hand, contradictory studies have found either no effect of reduced neurogenesis on hippocampal cognition (Groves et al., 2013; Saxe et al., 2006; Shors et al., 2002) or only on certain types of hippocampal cognitive tests (Shors et al., 2002). One study has even found that the absence of new neurons improves cognitive function (Saxe et al., 2007).”
§ Adult neurogenesis, glia, and the extracellular matrix > Function of adult-generated neurons
What the sources say
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In fact, seizures induce faster maturation of new granule neurons including early and more extensive mossy fiber sprouting and dendritic outgrowth as well as aberrant basal dendritic trees extending into the hilus, which receive recurrent excitatory drive from mossy fibers (Overstreet-Wadiche et al., 2006; Shapiro and Ribak, 2006) (Table 1).”
§ Adult neurogenesis, glia, and the extracellular matrix > Paradoxical effects of adult neurogenesis on hippocampal function
What the sources say
- Not checked yetcites Overstreet-Wadiche et al., 2006 source
- Not checked yetcites Shapiro and Ribak, 2006
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Adult neurogenesis in the hippocampus has been shown to be necessary for stress-induced social avoidance (Lagace et al., 2010), as well as in social cognition (Garrett et al., 2015) (Figure 1C).”
§ Adult neurogenesis, glia, and the extracellular matrix > Function of adult-generated neurons
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Manipulations used to reduce adult neurogenesis (transgenic, pharmacological, or focal x-irradiation approaches) affect hippocampal function specifically through loss of new neurons rather than through off-target effects.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As introduced above, functionally relevant aspects of new neuron connectivity likely involve not only connections with other neurons, but also associations with glial cells and the ECM.”
§ Adult neurogenesis, glia, and the extracellular matrix > Paradoxical effects of adult neurogenesis on hippocampal function
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“After these new cells are produced and start down the path toward neuronal differentiation, physical exercise enhances their survival, as it increases the development of their dendrites, and the complexity of both their afferent and efferent connections (Ambrogini et al., 2013; Gonçalves et al., 2016b; Llorens-Martín et al., 2015; Snyder et al., 2009b; Zhao et al., 2015) (Table 1).”
§ Adult neurogenesis, glia, and the extracellular matrix > Rewarding experiences alter adult neurogenesis
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Since integration of new granule neurons into the dentate gyrus unavoidably modifies the existing synaptic circuitry, one possible interpretation of these paradoxical findings is that damage-induced adult neurogenesis causes abnormal synaptic connectivity.”
§ Adult neurogenesis, glia, and the extracellular matrix > Paradoxical effects of adult neurogenesis on hippocampal function
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together, this evidence suggests that increased numbers of new neurons are associated with improved hippocampal function, while decreased numbers of new neurons are associated with deficient hippocampal function.”
§ Adult neurogenesis, glia, and the extracellular matrix > Function of adult-generated neurons
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Indeed, numerous studies have shown that physical exercise improves performance on hippocampus-dependent cognitive tasks (reviewed in Vivar et al., 2013) and reduces anxiety-like behaviors (Schoenfeld et al., 2013).”
§ Adult neurogenesis, glia, and the extracellular matrix > Rewarding experiences alter adult neurogenesis
What the sources say
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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 (Fanselow and Dong, 2010; Kheirbek et al., 2013).”
§ Adult neurogenesis, glia, and the extracellular matrix > Function of adult-generated neurons
What the sources say
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In fact, inhibiting adult neurogenesis reduces the frequency of chronic seizures along with seizure-related cognitive decline (Cho et al., 2015) as well as stroke-induced cognitive decline (Cuartero et al., 2019).”
§ Adult neurogenesis, glia, and the extracellular matrix > Paradoxical effects of adult neurogenesis on hippocampal function
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Brain injury models, such as stroke, seizure, and blunt trauma, all increase the rate of adult neurogenesis (Table 1), yet each of these conditions is associated with reduced cognitive function (Cuartero et al., 2019; Parent and Lowenstein, 2002; Sun et al., 2015).”
§ Adult neurogenesis, glia, and the extracellular matrix > Paradoxical effects of adult neurogenesis on hippocampal function
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Elimination or optogenetic silencing of adult-born neurons impairs pattern separation-like behaviors (Clelland et al., 2009; Danielson et al., 2016), while transgenic increases in adult neurogenesis enhance the ability of mice to distinguish between highly similar contexts (Sahay et al., 2011).”
§ Adult neurogenesis, glia, and the extracellular matrix > Function of adult-generated neurons
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Manipulations used to reduce adult neurogenesis (transgenic, pharmacological, or focal x-irradiation approaches) affect hippocampal function specifically through loss of new neurons rather than through off-target effects.
In the paper
“Treatment with the antidepressant fluoxetine resulted in an overproduction of new neurons in the adult hippocampus (Alves et al., 2017) (Table 1). This effect, which at first glance appeared to be beneficial, was surprisingly associated with cognitive decline, as well as increased susceptibility to stress-induced depression and excessive anxiety (Alves et al., 2017).”
§ Adult neurogenesis, glia, and the extracellular matrix > Paradoxical effects of adult neurogenesis on hippocampal function
What the sources say
- Not checked yetcites Alves et al., 2017 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The general suppressive effects of stress on adult neurogenesis can be largely attributed to the catabolic actions of glucocorticoids and the reduction in new neuron formation has been associated with impaired cognitive function (Bondi et al., 2008; Burgado et al., 2014).”
§ Adult neurogenesis, glia, and the extracellular matrix > Aversive experiences alter adult neurogenesis
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Adult neurogenesis, glia, and the extracellular matrix > Function of adult-generated neurons
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“releasing factors such as TNF-α or IL-1β, both of which influence synaptic plasticity (Prieto et al., 2018; Stellwagen and Malenka, 2006)”
§ Adult neurogenesis, glia, and the extracellular matrix > Glia regulate new neuron number and connectivity
What the sources say
- Not checked yetcites Prieto et al., 2018
- Not checked yetcites Stellwagen and Malenka, 2006
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Using viral-based methods, running has been found to increase the ratio of inhibitory interneuron versus excitatory mossy cell innervation onto new granule neurons (Sah et al., 2017; Vivar et al., 2016) as well as to enhance the number of new axon fibers projecting to the CA3 and CA2 subregions (Llorens-Martín et al., 2015).”
§ Adult neurogenesis, glia, and the extracellular matrix > Experiential regulation of new neuron connectivity
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“PNNs are lattice-like structures that form around the cell body and proximal dendrites of certain types of neurons (van ‘t Spijker and Kwok, 2017) and have been implicated in synaptic stabilization in the adult brain (Lensjø et al., 2017a).”
§ Adult neurogenesis, glia, and the extracellular matrix > Extracellular matrix regulation of new neuron number and connectivity
What the sources say
- Not checked yetcites van ‘t Spijker and Kwok, 2017
- Not checked yetcites Lensjø et al., 2017a
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“In the developing brain, peak synaptogenesis coincides with the differentiation and maturation of astrocytes (reviewed in Chung et al., 2015).”
§ Adult neurogenesis, glia, and the extracellular matrix > Glia regulate new neuron number and connectivity
What the sources say
- Not checked yetcites Chung et al., 2015 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Accumulating evidence suggests a role for the ECM in adult neurogenesis, as well as synaptogenesis, and synaptic signaling.”
§ Adult neurogenesis, glia, and the extracellular matrix > Extracellular matrix regulation of new neuron number and connectivity
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“but the extent to which these cells influence functional connectivity of new neurons remains incompletely explored.”
§ Adult neurogenesis, glia, and the extracellular matrix > Glia regulate new neuron number and connectivity
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Astrocytes within the adult hippocampus influence stem cell proliferation, their commitment to a neuronal phenotype, and their survival (Song et al., 2002), raising the possibility that there are distinct properties of astrocytes in the hippocampus that promote adult neurogenesis (Figure 2A).”
§ Adult neurogenesis, glia, and the extracellular matrix > Glia regulate new neuron number and connectivity
What the sources say
- Not checked yetcites Song et al., 2002 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Regulation of synaptic connectivity involves at least four main cellular/molecular components: the presynaptic neuron, postsynaptic neuron, glia, and the ECM, which together make up the “tetrapartite synapse” (Dityatev and Rusakov, 2011).”
§ Adult neurogenesis, glia, and the extracellular matrix > Experiential regulation of new neuron connectivity
What the sources say
- Not checked yetcites Dityatev and Rusakov, 2011 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Microglia also closely monitor neural activity and regulate synaptic plasticity.”
§ Adult neurogenesis, glia, and the extracellular matrix > Glia regulate new neuron number and connectivity
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Genetic disruption of Cx3cr1 decreases the number of new neurons (Bachstetter et al., 2011) supporting the importance of microglia-neuron communication in regulating adult neurogenesis.”
§ Adult neurogenesis, glia, and the extracellular matrix > Glia regulate new neuron number and connectivity
What the sources say
- Not checked yetcites Bachstetter et al., 2011 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Immune-deficient mice have impaired adult neurogenesis, even when housed in environmentally enriched conditions which typically increase stem cell proliferation, suggesting that immune molecules, potentially originating from microglia, are necessary for adult neurogenesis (Ziv et al., 2006).”
§ Adult neurogenesis, glia, and the extracellular matrix > Glia regulate new neuron number and connectivity
What the sources say
- Not checked yetcites Ziv et al., 2006 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Environmental enrichment-induced increases in adult neurogenesis are associated with increased synthesis of chondroitin sulfate proteoglycans, which is prevented by chondroitin sulfate proteoglycan synthesis disruption (Yamada et al., 2018).”
§ Adult neurogenesis, glia, and the extracellular matrix > Extracellular matrix regulation of new neuron number and connectivity
What the sources say
- Not checked yetcites Yamada et al., 2018 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Chondroitin sulfate proteoglycans, structural ECM components, are known to surround new neurons in the hippocampus, and recent work has shown that this molecule is important for the production and differentiation of new neurons in adulthood (Yamada et al., 2018).”
§ Adult neurogenesis, glia, and the extracellular matrix > Extracellular matrix regulation of new neuron number and connectivity
What the sources say
- Not checked yetcites Yamada et al., 2018 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Depletion of chondroitin sulfate proteoglycans in the hippocampus decreases new neuron formation and dendritic tree maturation, and produces cognitive impairment (Figure 3A).”
§ Adult neurogenesis, glia, and the extracellular matrix > Extracellular matrix regulation of new neuron number and connectivity
What the sources say
- Not checked yetcites Yamada et al., 2018 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“PNNs are specialized extracellular structures composed of tenascin-R, hyaluronan, chondroitin sulfate proteoglycans, and link proteins (Figure 3C), which play important roles in brain plasticity during development and in adulthood (Sorg et al., 2016).”
§ Adult neurogenesis, glia, and the extracellular matrix > Potential role for perineuronal nets in new neuron connectivity
What the sources say
- Not checked yetcites Sorg et al., 2016 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Reelin is also known to enhance hippocampal synaptic plasticity (Pujadas et al., 2010; Weeber et al., 2002) by altering the composition of NMDA receptor subunits and promoting surface clustering of AMPA receptors (Qiu et al., 2006) (Figure 3B).”
§ Adult neurogenesis, glia, and the extracellular matrix > Extracellular matrix regulation of new neuron number and connectivity
What the sources say
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For instance, the ECM may spatially restrict microglial and astrocytic processes from invading the perisynaptic space, thus ECM remodeling may prompt invasion of glial cells, which in turn may regulate synaptic signaling.”
§ Adult neurogenesis, glia, and the extracellular matrix > Extracellular matrix regulation of new neuron number and connectivity
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In general, PNNs restrain plasticity and promote synaptic stabilization in the adult brain.”
§ Adult neurogenesis, glia, and the extracellular matrix > Potential role for perineuronal nets in new neuron connectivity
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“In the developing and adult hippocampus, tenascin-R deficiency reduces the number of proliferating stem cells, while increasing the number of cells committed to a neuronal phenotype (Xu et al., 2014).”
§ Adult neurogenesis, glia, and the extracellular matrix > Extracellular matrix regulation of new neuron number and connectivity
What the sources say
- Not checked yetcites Xu et al., 2014
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Since activation of PV+ interneurons has been shown to promote new neuron cell survival while suppression of PV+ interneuron activity reduces new neuron cell survival (Song et al., 2013)”
§ Adult neurogenesis, glia, and the extracellular matrix > Potential role for perineuronal nets in new neuron connectivity
What the sources say
- Not checked yetcites Song et al., 2013 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“has been shown to play a critical role in neuronal migration and synaptic plasticity (reviewed in Lee and D’Arcangelo, 2016).”
§ Adult neurogenesis, glia, and the extracellular matrix > Extracellular matrix regulation of new neuron number and connectivity
What the sources say
- Not checked yetcites Lee and D’Arcangelo, 2016 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Studies suggest that tenascins are a critical component of PNNs (Suttkus et al., 2014), which surround many of the neurons that are postsynaptic to adult-generated granule cells.”
§ Adult neurogenesis, glia, and the extracellular matrix > Extracellular matrix regulation of new neuron number and connectivity
What the sources say
- Not checked yetcites Suttkus et al., 2014 source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In the adult mouse hippocampus, reelin deficiency reduces neurogenesis (Won et al., 2006), while reelin overexpression increases neurogenesis (Pujadas et al., 2010) (Figure 3A).”
§ Adult neurogenesis, glia, and the extracellular matrix > Extracellular matrix regulation of new neuron number and connectivity
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Several studies have shown that tenascin-R knockout mice have altered synaptic plasticity in the hippocampus, including impaired LTP and increased basal excitatory transmission (Bukalo et al., 2001; Gurevicius et al., 2004; Saghatelyan et al., 2001).”
§ Adult neurogenesis, glia, and the extracellular matrix > Extracellular matrix regulation of new neuron number and connectivity
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Tenascin-R, an ECM glycoprotein, is also important for new neuron production and synaptic plasticity in the adult hippocampus.”
§ Adult neurogenesis, glia, and the extracellular matrix > Extracellular matrix regulation of new neuron number and connectivity
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Overexpression of reelin accelerates dendritic development of adult-born neurons and increases the number of synaptic contacts in the dentate gyrus (Pejadas et al., 2010; Teixeira et al., 2012), whereas the absence of reelin signaling reduces dendritic tree complexity on new granule neurons (Teixeira et al., 2012).”
§ Adult neurogenesis, glia, and the extracellular matrix > Extracellular matrix regulation of new neuron number and connectivity
What the sources say
- Not checked yetcites Pejadas et al., 2010
- Not checked yetcites Teixeira et al., 2012 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“The reelin pathway also participates in the integration of adult-born neurons into the hippocampal circuitry by regulating spine morphology, spine type, and the number of synaptic connections on new granule neurons as well as the degree of perisynaptic astroglial ensheathment of new granule neuron synapses (Bosch et al., 2016).”
§ Adult neurogenesis, glia, and the extracellular matrix > Extracellular matrix regulation of new neuron number and connectivity
What the sources say
- Not checked yetcites Bosch et al., 2016 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Mice deficient in MMP9 have impaired hippocampal LTP, including at mossy fiber-CA3 synapses, which is restored by adding recombinant active MMP9 (Nagy et al., 2006; Weira et al., 2013).”
§ Adult neurogenesis, glia, and the extracellular matrix > Extracellular matrix regulation of new neuron number and connectivity
What the sources say
- Not checked yetcites Nagy et al., 2006 source
- Not checked yetcites Weira et al., 2013
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“one possibility is that changes in the number of new neurons, which alter the overall excitability of the hippocampus (Ikrar et al., 2013), may then regulate the expression of PNNs at postsynaptic sites.”
§ Adult neurogenesis, glia, and the extracellular matrix > Potential role for perineuronal nets in new neuron connectivity
What the sources say
- Not checked yetcites Ikrar et al., 2013 source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“PNNs have been relatively uninvestigated in the context of adult neurogenesis.”
§ Adult neurogenesis, glia, and the extracellular matrix > Potential role for perineuronal nets in new neuron connectivity
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Physical exercise, which increases new neuron production and improves behaviors associated with the hippocampus, also stimulates astrocyte growth (Brockett et al., 2015; Fahimi et al., 2017) and reduced microglial reactivity (Kohman et al., 2012, 2013).”
§ Adult neurogenesis, glia, and the extracellular matrix > Proposed models and remaining questions
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“while PNNs may attract or repel axons of new neurons.”
§ Adult neurogenesis, glia, and the extracellular matrix > Proposed models and remaining questions
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Stress, on the other hand, which diminishes adult neurogenesis and impairs hippocampal function, has been shown to reduce the size and number of astrocytes (Czéh et al., 2006; Tynan et al., 2013) as well as trigger microglial reactivity (Kreisel et al., 2014; Llorens-Martín et al., 2016).”
§ Adult neurogenesis, glia, and the extracellular matrix > Proposed models and remaining questions
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“For example, seizures stimulate adult neurogenesis and impair hippocampal function.”
§ Adult neurogenesis, glia, and the extracellular matrix > Proposed models and remaining questions
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
Manipulations used to reduce adult neurogenesis (transgenic, pharmacological, or focal x-irradiation approaches) affect hippocampal function specifically through loss of new neurons rather than through off-target effects.
“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.”
The paper relies on this without support.
The connectivity of new neurons in the adult hippocampus is highly relevant to their functional influence.
“It has become increasingly clear that the connectivity of new neurons in the adult hippocampus is highly relevant to their functional influence.”
The paper relies on this without support.
All components of the synapse, including glia, the ECM, and the presynaptic and postsynaptic neurons must be considered in an effort to elucidate the diverse effects new neurons have on brain function.
“All components of the synapse, including glia, the ECM, and the presynaptic and postsynaptic neurons must be considered in an effort to elucidate the diverse effects new neurons have on brain function.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“A previous study has reported that microglia participate in stem cell proliferation and survival through their release of important trophic factors and anti-inflammatory cytokines.16”
From Microglia secrete miR-146a-5p-containing exosomes to regulate neurogenesis in depression (2022) · cites this paper as [16]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Saxe et al. (2006) is cited as finding no cognitive effect, but its listed title reports an impairment
MinorThe text places Saxe et al. (2006) among studies finding no effect of reduced neurogenesis on hippocampal cognition. Its reference title instead states that ablation impairs contextual fear conditioning, a test the text itself identifies as hippocampal-dependent cognition.
“On the other hand, contradictory studies have found either no effect of reduced neurogenesis on hippocampal cognition (Groves et al., 2013; Saxe et al., 2006; Shors et al., 2002)”
“Saxe MD, Battaglia F, Wang JW, Malleret G, David DJ, Monckton JE, Garcia AD, Sofroniew MV, Kandel ER, Santarelli L, Hen R, and Drew MR (2006). Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus.”
Citations
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Self-citationReelin and ApoE receptors cooperate to enhance hippocampal synaptic plasticity and learning
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Microglia secrete miR-146a-5p-containing exosomes to regulate neurogenesis in depression
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The Role of Astrocytes in the Neurorepair Process
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Communication, Cross Talk, and Signal Integration in the Adult Hippocampal Neurogenic Niche
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Metadata
- Authors
- Cope, E. C., & Gould, E.
- Affiliations
- Princeton University (US)
- Corresponding author
- Gould, Elizabeth
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2019-05
- Volume
- 24
- Issue
- 5
- Pages
- 690-705
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC7961263
- OpenAlex
- W2942783247
- Semantic Scholar
- 194e87b067e2102bb5954d25a3fad0864c796ea7
- Cited by
- 236
- References
- 205
- Citations by year
- 2026: 16 · 2025: 36 · 2024: 48 · 2023: 41 · 2022: 41 · 2021: 33 · 2020: 17 · 2019: 4
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (MH117459-01, T32MH065214)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- adult neurogenesis, hippocampus, glia, extracellular matrix, stem/progenitor cells, hippocampal circuitry, learning and memory, social behavior
- MeSH terms
- Adult, Animals, Astrocytes, Cell Differentiation, Extracellular Matrix, Hippocampus, Humans, Neurons, Oligodendroglia, Microglia, Neurogenesis, Neural Stem Cells
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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