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Neurogenesis in the Hippocampus and Learning

Neurogenesis in the Hippocampus and Learning. Andreas Gustafsson. http://www.bris.ac.uk/Depts/Synaptic/info/pathway/figs/hippocampus.gif. Hippocampus Shows Spatial Learning. Place specific behavior is observed in CA3 and CA1, as well as the Entorhinal cortex (Fyhn).

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Neurogenesis in the Hippocampus and Learning

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  1. Neurogenesis in the Hippocampus and Learning Andreas Gustafsson

  2. http://www.bris.ac.uk/Depts/Synaptic/info/pathway/figs/hippocampus.gifhttp://www.bris.ac.uk/Depts/Synaptic/info/pathway/figs/hippocampus.gif

  3. Hippocampus Shows Spatial Learning Place specific behavior is observed in CA3 and CA1, as well as the Entorhinal cortex (Fyhn)

  4. Cartoon Wiring of the Hippocampus EC- Entorhinal Cortex SUB – Subicular areas DG –Dentate Gyrus SI – Sensory Information

  5. Dentate Gyrus • A portion of the hippocampus • Three layers- molecular, granule, hilus • Granule Cells have axons that synapse on CA3 pyramidal cells • Recent Studies have shown that the dentate gyrus undergoes adult neurogenesis, on the order of thousands of cells (Cameron)

  6. What are these new cells doing? • What are the thousands of new cells generated each day doing? • What are they responsible for? • Is it important for memory?

  7. General Approach 1) Block cell division 2) Measure behavioral effect 3) Show anatomical difference between treated and control animals

  8. Methods • BrdU – labeled thymidine analog, indicates mitosis • Irradiation- kills proliferating cells (Snyder) • MAM – methylates DNA, preventing mitosis (Bruel-Jungerman)

  9. Methods • Water Maze (Snyder) • Behavior in a novel environment(Bruel-Jungerman)

  10. Cell Staining is Pretty

  11. Behavioral Change From Bruel-Jungerman

  12. Effect of Environmental Enrichment and MAM treatment- Cell Count

  13. Water Maze Training (Snyder)

  14. Conclusions • Neurogenesis of granule cells is necessary for long term learning, seemingly on a two week time course. • Neurogenesis is promoted by an enriched environment.

  15. Pathologies Associated with Aberrant Granule Cell Behavior • Epileptic patients and model systems show different granule cell behavior and morphology. This observation begs the question “Why?”

  16. Normal Granule Cell Proliferation Shapiro

  17. Epileptic Phenotype • A seizer seems to generate to two new cell types: hilar ectopic granule cells (HEGC) and and cells with hilar basal dendrites (HBD)

  18. Epileptic Granule Cell Proliferation Shapiro

  19. Hypothesis • The event of a seizure causes massive cell death in the hilar layer. • Granule cells, which are always dividing, fill in the gaps in the hilar layer. • Abberant placement of granule cells leads to recurrent excitatory loops.

  20. References • Spatial Representation in the Entorhinal Cortex, Marianne Fyhn, Sturla Molden, Menno P.Witter, Edvard I.Moser, May-Britt Moser. • Brown, T.H. and Zador, A.M. (1990). Hippocampus. In The synaptic Organization of the Brain, 3rd ed. (G.M. Shepherd). Oxford University Press. • Cameron,H.A.&McKay,R.D.G.(2001)Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus.J.Comp.Neurol.,435 ,406 .417. • Bruel-Jungerman, Elodie, Laroche, Serge & Rampon, Claire (2005)New neurons in the dentate gyrus are involved in the expression of enhanced long-term memory following environmental enrichment. European Journal of Neuroscience21 (2), 513-521. • A role for adult neurogenesis in spatial long-term memory J.S. Snyder, N.S. Hong, R.J. McDonald and J.M. Wojtowicza Neuroscience Volume 130, Issue 4, 2005, Pages 843-852 • Integration of newly born dentate granule cells into adult brains: hypotheses based on normal and epileptic rodents. Shapiro LA, Ribak CE. Brain Res Brain Res Rev. 2005 Feb;48(1):43-56.

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