Pharmacological Enhancement of Adult Hippocampal Neurogenesis Improves Behavioral Pattern Separation in Young and Aged Male Mice.

Background: Impairments in behavioral pattern separation (BPS)-the ability to distinguish between similar contexts or experiences-contribute to memory interference and overgeneralization seen in many neuropsychiatric conditions, including depression, anxiety, posttraumatic stress disorder, dementia, and age-related cognitive decline. Although BPS relies on the dentate gyrus and is sensitive to changes in adult hippocampal neurogenesis, its significance as a pharmacological target has not been tested.

Methods: In this study, we applied a human neural stem cell high-throughput screening cascade to identify compounds that increase human neurogenesis.

Optimal sparsity in autoencoder memory models of the hippocampus.

Storing complex correlated memories is significantly more efficient when memories are recoded to obtain compressed representations. Previous work has shown that compression can be implemented in a simple neural circuit, which can be described as a sparse autoencoder. The activity of the encoding units in these models recapitulates the activity of hippocampal neurons recorded in multiple experiments.

Adult Neurogenesis, Context Encoding, and Pattern Separation: A Pathway for Treating Overgeneralization.

In mammals, the subgranular zone of the dentate gyrus is one of two brain regions (with the subventricular zone of the olfactory bulb) that continues to generate new neurons throughout adulthood, a phenomenon known as adult hippocampal neurogenesis (AHN) (Eriksson et al., Nat Med 4:1313-1317, 1998; García-Verdugo et al., J Neurobiol 36:234-248, 1998).

Effects of electroconvulsive shock on the function, circuitry, and transcriptome of dentate gyrus granule neurons.

Therapeutic use of electroconvulsive shock (ECS) is particularly effective for treatment-resistant depression. Like other more common forms of antidepressant treatment such as SSRIs, ECS has been shown to increase neurogenesis in the hippocampal dentate gyrus of rodent models. Yet the question of how ECS-induced neurogenesis supports improvement of depressive symptoms remains unknown.

Switching on generalized fear.

Stress induces a neurotransmitter switch that leads to fear in harmless situations.