Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation

Abstract

Adult hippocampal neurogenesis is a unique form of neural circuit plasticity that results in the generation of new neurons in the dentate gyrus (DG) throughout life 1, 2. Adult-born neurons exhibit heightened synaptic plasticity during their maturation 3 and can account for up to ten percent of the entire granule cell population 4. Moreover, levels of adult hippocampal neurogenesis are elevated by interventions associated with beneficial effects on cognition and mood such as learning 5, environmental enrichment 6, exercise 6 and chronic antidepressant treatment 7–10. Together, these properties of adult neurogenesis suggest that it may 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 11 and some of the behavioural effects of antidepressants 8–10, 12, 13, it is unknown whether increasing adult hippocampal neurogenesis is sufficient to improve cognition and mood. Here we show that inducible genetic expansion of the population of adult-born neurons by enhancing their survival improves performance in a specific cognitive task in which an animal must distinguish between two similar contexts. 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, suggestive 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. In contrast, increasing adult hippocampal neurogenesis, on its own, does not produce an anxiolytic or antidepressant-like behavioural response. Together, our findings suggest that strategies designed to specifically increase adult hippocampal neurogenesis, by targeting cell death of adult-born neurons or other means, may have therapeutic potential for reversing impairments in pattern separation such as that seen during normal aging 14, 15.

Cortical pattern separation and item-specific memory encoding

“…In RIFG, curve fitting analysis provided further support for conceptual and perceptual pattern separation. These findings are consistent with the suggestion that cortical pattern separation at encoding contributes to accurate recognition memory (e.g., Sahay et al, 2011;Schacter et al, 1998;Stark et al, 2013Wilson et al, 2006. The assignment of unique neural representations to novel input (pattern separation) may aid formation of item-specific memory traces which later enable successful recognition of studied items (Kirwan and Stark, 2007).…”

“…Although pattern separation is by definition an encoding process, and pattern completion a retrieval process, either or both can be elicited by a single event, whether novel or previously encountered (Hunsaker and Kesner, 2013). Efficient pattern separation at encoding is thought to contribute to later mnemonic discrimination between events with similar representations, while false recognition of similar events can result from inefficient pattern separation or dominance of pattern completion at encoding (Sahay et al, 2011;Stark et al, 2013;Wilson et al, 2006). However the precise mechanisms by which pattern separation and completion at encoding contribute to memory outcomes remain unknown, and it remains to be established whether and how neocortex complements the central role of the hippocampus in these computations.…”

Evidence of an amnesia-like cued-recall memory impairment in nondementing idiopathic Parkinson's disease

“…An interesting, if speculative, possibility is that a component of this atrophy is decreased adult neurogenesis in the dentate gyrus of the hippocampal (for reviews, see Kemperman & Kroneberg, 2003;Sahay & Hen, 2007) . Such decreased neurogenesis in the anterior dentate gyrus would negatively disrupt cellular processes underlying pattern separation in the CA1-4/dentate gyrus subfields of the hippocampus (e.g., Sahay, et al, 2011). .…”

Heat-Induced Antigen Retrieval: An Effective Method to Detect and Identify Progenitor Cell Types during Adult Hippocampal Neurogenesis

“…Over the past decade, the field of adult hippocampal neurogenesis has seen significant work. The region has attracted much interest since newborn neurons in the SGZ contribute to enhanced neural plasticity that can sustain specific brain functions [1][2][3][4][5] . Adult hippocampal neurogenesis has been implicated to play important roles in mood regulation, regeneration, and learning and memory.…”