Neurotopic

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Neurotopic 1 Neurogenesis

• A role for adult neurogenesis in spatial
  long-term memory

Sabrina Lemire-Rodger PSYC 371, October 4th, 2007
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Intro background

• Dentate Gyrus of the Hippocampus
• Part of the medial temporal lobe
• Rare area where adult neurogenesis occurs
• Has been linked to memory and spatial learning

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Intro background
Neurogenesis

• Granule cells in the DG
• Proliferate
• Migrate
• Differentiate

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Intro background Perforant
pathway

• Input from the Entorhinal cortex
• DG project to interneurons in CA3
• CA3 to Ca1
• Output to neocortex limbic system

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Intro background Effects of
Neurogenesis

• Enriched environment proliferation and survival
  of new cells

? Happy rat

• Plays role in behavioural effects of
  antidepressants

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Methods

• General experimental design
• 3 groups Irradiated(IRR) rats, normal learning
  rats cage controls

• Learn either a spatial or cued version of the
  Morris Water Maze, and probe-tested wks later
• 2 hypotheses 1) IRR learners will not perform
  upon probing in spatial task. 2) Learning will
  promote proliferation survival of new cells.

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Methods Schedule

• 40 days old whole brain Irradiation
• 3 weeks later labeling of new cells
• One week after that MWM training
• Re-testing 1, 2 and 4 weeks after
• Day after probe testing Immunochemistry
  electrophysiology

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Methods Morris Water Maze

• Spatial version submerged platform always in
  same quadrant of the maze. Rats find it using
  visual cues around the room
• Cued version a black white striped hanging rod
  indicated the position of the platform, also
  constant quadrant.
• Probe-testing performance measured by amount of
  time rats spend it quadrant where the platform
  used to be.

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Methods Labeling electrophysiology

• Pre-learning BrdU Thymidine analog
• Post-probing
• Immunoflurescent labeling of CaBp BrdU
• Electro-recording of neurons in DG CA1

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Results Irradiation

• Empty Symbols represent IRR Learners,
• Filled symbols represent Shams
• Circles represent BrdU-labeled neurons,
• Squares represent non-neuronal cells

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Results Main finding
Irradiation affects long-term ( 2 wks) spatial
memory!
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Results What was not found
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Results (lack of) Physiological differences
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Results testing for Alternative explanations

• General detrimental effect of radiation?
  shifted learning task one week, same results.
• All learning impaired? cued task unaffected.
• Only neurons of a specific age influences
  long-term spatial retention. Irradiation
  immediately before or after training has no
  effect.

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Discussion

• Revisiting the hypotheses
• Yes. Irradiated learners were not able to perform
  the spatial task when it relied on long-term
  memory.
• No. In this experiment, there was no relation
  between granule cell proliferation survival and
  learning.

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Discussion Explaining the results

• New neurons 4-28 days
• Young neurons plasticity.
• More long-term storing potential
• Role in consolidation vs. acquisition
• Vs. mature neurons
• Acquisition, short-term memory
• Retention of simple tasks

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Discussion Induction thresholds LTP

• Younger neurons have a lower Induction
  threshold that facilitates the creation of new
  long-term memories.
• Long-Term Potentiation (LTP) is the potential for
  a neuron to turn experience into stored memory
• LTP is a possible mechanism for memory

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Discussion Questions that remain

• How?
• Understanding the biological basis of memory
  Plasticity offered by high cell turn over may be
  the key to storing memories.
• Where?
• Granule cells in DG are important but where are
  the memories permanently stored? In the
  hippocampus or transferred to the neocotex?

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Discussion Un-replicated data

• Unlike other studies, this study did not find
• a correlation between the amount of new cells
  created in light of learning
• or the survival of new cells in light of
  learning
• This may be because of the specificity of sets of
  neurons, tasks and timing.

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Discussion food for thought
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Discussion Real world applications

• The authors relate this study to memory deficits
  in irradiated humans, especially children, whom
  have a higher level of neurogenesis.

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The end! Reference

• Snyder, J.S., Hong, N.S., McDonald, R.J.
  Wojtowicz, J.M. (2005). A role for adult
  neurogenesis in spatial long-term memory.
  Neuroscience, 130, 842-852.