Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation

By Amar Sahay, Kimberly N. Scobie, Alexis S. Hill, C. O’Carroll, M. Kheirbek, N. Burghardt, André A. Fenton, A. Dranovsky, R. Hen. 2011

1,595 citations recorded by the source corpus.

Adult hippocampal neurogenesis is a unique form of neural circuit plasticity that results in the generation of new neurons in the dentate gyrus throughout life. Neurons that arise in adults (adult-born neurons) show heightened synaptic plasticity during their maturation and can account for up to ten per cent of the entire granule cell population. Moreover, levels of adult hippocampal neurogenesis are increased by interventions that are associated with beneficial effects on cognition and mood, such as learning, environmental enrichment, exercise and chronic treatment with antidepressants. Together, these properties of adult neurogenesis indicate that this process could be harnessed to improve hippocampal functions. However, despite a substantial number of studies demonstrating that adult-born neurons are necessary for mediating specific cognitive functions, as well as some of the behavioural effects of antidepressants, it is unknown whether an increase in adult hippocampal neurogenesis is sufficient to improve cognition and mood. Here we show that inducible genetic expansion of the population of adult-born neurons through enhancing their survival improves performance in a specific cognitive task in which two similar contexts need to be distinguished. Mice with increased adult hippocampal neurogenesis show normal object recognition, spatial learning, contextual fear conditioning and extinction learning but are more efficient in differentiating between overlapping contextual representations, which is indicative of enhanced pattern separation. Furthermore, stimulation of adult hippocampal neurogenesis, when combined with an intervention such as voluntary exercise, produces a robust increase in exploratory behaviour. However, increasing adult hippocampal neurogenesis alone does not produce a behavioural response like that induced by anxiolytic agents or antidepressants. Together, our findings suggest that strategies that are designed to increase adult hippocampal neurogenesis specifically, by targeting the cell death of adult-born neurons or by other mechanisms, may have therapeutic potential for reversing impairments in pattern separation and dentate gyrus dysfunction such as those seen during normal ageing.

Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience

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Citations in the corpus

Human Hippocampal Neurogenesis Persists throughout Aging (2018, neutral): “The ability to separate similar memory patterns (Sahay et al., 2011) and recover from stress (Schloesser et al.”
Dynamics of hippocampal neurogenesis in adult humans (2013, positive): “, 2004), which is critical for their role in mediating pattern separation in memory formation and cognition in rodents (Clelland et al., 2009; Nakashiba et al., 2012; Sahay et al., 2011).”
Adult hippocampal neurogenesis and its role in Alzheimer's disease (2011, background): “A growing body of evidence supports the view that promotion of adult hippocampal neurogenesis improves pattern separation and spatial memory [8,9].”
Astrocytes: a central element in neurological diseases (2016, neutral): “tern separation [1, 50, 115, 191].”
Neuronal activity-dependent control of postnatal neurogenesis and gliogenesis (2018, neutral): “…(a) newly generated neurons in the adult hippocampus contribute importantly to learning and memory (Goncalves et al. 2016, Kropff et al. 2015, Sahay et al. 2011), (b) LV neurogenesis and gliogenesis play critical roles in olfactory-based social learning (Mak & Weiss 2010, Mak et al. 2007,…”
Pattern separation in the hippocampus through the eyes of computational modeling (2017, background): “…undergo adult neurogenesis in the brain and new-born GCs are considered to play a key role in learning and memory (Appleby, Kempermann, & Wiskott, 2011; Clelland et al., 2009; Sahay et al., 2011a) processes, including pattern separation (Kesner & Rolls, 2015; van Praag, Kempermann, & Gage, 1999).”
Spatial representations of granule cells and mossy cells of the dentate gyrus (2017, background): “Adult-born granule cells strongly influence performance on tasks thought to rely on pattern separation (Clelland et al., 2009; Sahay et al., 2011), but their spatial firing properties during normal exploration remain unclear (but see Danielson et al.”
Adult hippocampal neurogenesis, Rho kinase inhibition and enhancement of neuronal survival. (2013, background): “…with regards to neurogenesis and some hippocampal dependent tasks, it is noteworthy that novel object recognition, which was unaltered in our paradigm, is not affected by ablation (Madsen et al., 2003, Rola et al., 2004, Clelland et al., 2009) or enhancement of neurogenesis (Sahay et al., 2011).”
Distinct Contribution of Adult-Born Hippocampal Granule Cells to Context Encoding (2016, neutral): “Hypotheses attempting to explain the role of abGCs range from modulating the activity of mature GCs (mGCs) through interactions with local interneurons, to themselves providing the DG’s principal output signals (Piatti et al., 2013; Sahay et al., 2011b).”
Resolving new memories: a critical look at the dentate gyrus, adult neurogenesis, and pattern separation (2011, background): “As a result, an increase in the number of immature neurons improved animals' performance on the tasks demanding high memory resolution (Creer et al., 2010; Sahay et al., 2011), whereas a decrease in neurogenesis resulted in deficits in solving these tasks (Clelland et al., 2009).”
Benzodiazepines And The Potential Trophic Effect Of Antidepressants On Dentate Gyrus Cells In Mood Disorders (2014, neutral): “Increased neurogenesis and cell survival improves pattern discrimination (Sahay et al., 2011).”
Pattern separation: a common function for new neurons in hippocampus and olfactory bulb (2011, neutral): “To directly address this possibility, Sahay and colleagues developed a genetic strategy to selectively increase adult neurogenesis (Sahay et al., 2011).”
The role of adult hippocampal neurogenesis in brain health and disease (2018, background): “Manipulations to increase neurogenesis can have the opposite effect, improving the ability to distinguish nearby locations on a touchscreen task [68] or similar fear conditioning contexts [69].”
Functional Dissociation of Adult-Born Neurons Along the Dorsoventral Axis of the Dentate Gyrus (2014, background): “…in deficits ranging from spatial learning and memory (Raber et al., 2004; Clelland et al., 2009; Deng et al., 2010; Arruda-Carvalho et al., 2011; Sahay et al., 2011; Denny et al., 2012) to behavioral responses to antidepressants and regulation of the hypothalamic-pituitary-adrenal stress axis…”