Neonatal vs. adult unilateral hippocampal lesions: differential alterations in contralateral hippocampal theta rhythm.
Subcortical damage often has more severe consequences in neonates than in adults. For example, unilateral hippocampal lesions in adult rats typically lead to transient memory deficits, whereas neonatal lesions cause lasting learning impairment. We hypothesized that the defects triggered by unilateral damage may include synaptic dysfunction in the contralateral hippocampus. Consequently, we examined the hippocampal theta rhythm, an EEG pattern thought to be associated with learning. Initial comparisons between intact and lesioned rats revealed no obvious differences in basal theta rhythm properties. However, manipulations of ascending brainstem projections to hippocampus with drugs specific for serotonergic, noradrenergic and cholinergic receptors uncovered differences. Antagonism of 5-HT3 receptors known to promote learning significantly increased theta frequency in controls and adult lesioned rats, but not after neonatal damage. In contrast, blockade of noradrenergic-alpha2 receptors had no effect. Antagonism of cholinergic receptors which typically impairs learning disrupted theta and caused irregular, high-amplitude activity that was significantly more pronounced in the lesioned groups. A final approach involved pharmacological facilitation of AMPA receptor-mediated currents, using a drug which enhances memory. This treatment significantly enhanced theta frequency in controls and animals lesioned as adults. In contrast, it failed to do so in rats lesioned at birth. These observations suggest that latent dysfunction in contralateral hippocampal physiology may contribute to the lasting memory deficits seen after unilateral hippocampal lesion in neonates.
van Praag
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Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, UMDNJ, Piscataway 08854, USA.
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Stäubli
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D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D007839:Functional Laterality / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D019329:Idazoxan / Q000494:pharmacology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D017294:Ondansetron / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000819:agonists; D012601:Scopolamine / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013826:Theta Rhythm
D000317:Adrenergic alpha-Antagonists; C104414:BDP 20; D018727:Muscarinic Antagonists; D011759:Pyrrolidines; D018091:Receptors, AMPA; D012702:Serotonin Antagonists; D017294:Ondansetron; D012601:Scopolamine; D019329:Idazoxan