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Related Experiment Videos

Ectopic noradrenergic hyperinnervation does not functionally compensate for neonatal forebrain acetylcholine lesion.

B A Pappas1, T Nguyen, B Brownlee

  • 1Institute of Neuroscience, Life Sciences Research Centre, Carleton University, Ontario, K1S 5B6, Ottawa, Canada. bpappas@ccs.carleton.ca

Brain Research
|June 6, 2000
PubMed
Summary

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Ectopic noradrenergic ingrowths do not compensate for neonatal acetylcholine depletion in rats. Despite significant forebrain neurotransmitter loss, adult rats showed intact behavior on most tasks, with minor working memory deficits.

Area of Science:

  • Neuroscience
  • Behavioral Neuroscience
  • Neurobiology

Background:

  • Neonatal lesions of forebrain acetylcholine (ACH) neurons in rats result in ectopic hippocampal ingrowths.
  • The functional significance of these ingrowths in compensating for ACH denervation is unknown.

Purpose of the Study:

  • To investigate whether ectopic hippocampal noradrenergic (NE) ingrowths compensate for neonatal forebrain ACH depletion.
  • To assess the behavioral impact of combined neonatal ACH and NE denervation.

Main Methods:

  • Neonatal rats received 6-hydroxydopamine (6-OHDA) to block NE ingrowths and/or 192 IgG-saporin to lesion ACH neurons.
  • Immunoreactivity for p75 neurotrophin receptor (p75(NTR)) and dopamine-beta-hydroxylase (DBH) was assessed.
  • Adult rats were tested on the Morris water maze, delayed spatial alternation (DSA), and radial arm maze (RAM).

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Main Results:

  • 192 IgG-saporin treatment reduced p75(NTR) neurons; 6-OHDA abolished DBH terminals.
  • Ectopic DBH and p75(NTR) varicosities in the hippocampus were eliminated by 6-OHDA.
  • No treatment effects were observed on the Morris water maze.
  • 192 IgG-saporin caused perseveration in DSA and increased working memory errors in RAM.
  • Combined 6-OHDA and 192 IgG-saporin treatment yielded similar results to 192 IgG-saporin alone.

Conclusions:

  • Ectopic hippocampal NE ingrowths do not functionally compensate for neonatal ACH lesions.
  • Neonatal ACH lesions impair working memory but not short-term memory, as evidenced by RAM and DSA performance.
  • Rats with combined neonatal ACH and NE denervation exhibit remarkably intact behavior.