Neurogenesis in the Hippocampus and Learning

Neurogenesis in the
Hippocampus and Learning
Andreas Gustafsson
Hippocampus Shows Spatial
Place specific behavior is observed in CA3 and CA1, as
well as the Entorhinal cortex (Fyhn)
Cartoon Wiring of the
EC- Entorhinal Cortex
DG –Dentate Gyrus
SUB – Subicular areas
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
• BrdU – labeled thymidine analog, indicates
• Irradiation- kills proliferating cells (Snyder)
• MAM – methylates DNA, preventing
mitosis (Bruel-Jungerman)
• Water Maze (Snyder)
• Behavior in a novel environment(BruelJungerman)
Cell Staining is Pretty
Behavioral Change
From Bruel-Jungerman
Effect of Environmental Enrichment
and MAM treatment- Cell Count
Water Maze Training
• Neurogenesis of granule cells is
necessary for long term learning,
seemingly on a two week time course.
• Neurogenesis is promoted by an enriched
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
Epileptic Phenotype
• A seizer seems to generate to two new cell
types: hilar ectopic granule cells (HEGC)
and and cells with hilar basal dendrites
Epileptic Granule Cell Proliferation
• 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.
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
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
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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