Neurogenesis in the Hippocampus and Learning

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Presentation transcript:

Neurogenesis in the Hippocampus and Learning Andreas Gustafsson

http://www. bris. ac. uk/Depts/Synaptic/info/pathway/figs/hippocampus 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)

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

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)

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?

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

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

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

Cell Staining is Pretty

Behavioral Change From Bruel-Jungerman

Effect of Environmental Enrichment and MAM treatment- Cell Count

Water Maze Training (Snyder)

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.

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?”

Normal Granule Cell Proliferation Shapiro

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)

Epileptic Granule Cell Proliferation Shapiro

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.

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 Neuroscience 21 (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.