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)
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?”
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)
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.
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