Neurogenesis in the Hippocampus and Learning

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Neurogenesis in the Hippocampus and Learning

• Andreas Gustafsson

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http//www.bris.ac.uk/Depts/Synaptic/info/pathway/
figs/hippocampus.gif
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Hippocampus Shows Spatial Learning
Place specific behavior is observed in CA3 and
CA1, as well as the Entorhinal cortex (Fyhn)
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Cartoon Wiring of the Hippocampus
EC- Entorhinal Cortex SUB
Subicular areas DG Dentate Gyrus
SI Sensory Information
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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)

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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?

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General Approach

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

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Methods

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

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Methods

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

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Cell Staining is Pretty
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Behavioral Change
From Bruel-Jungerman
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Effect of Environmental Enrichment and MAM
treatment- Cell Count
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Water Maze Training
(Snyder)
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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.

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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?

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Normal Granule Cell Proliferation
Shapiro
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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)

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Epileptic Granule Cell Proliferation
Shapiro
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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.

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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 Feb48(1)43-56.