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 tr iggered by unilateral damage may include synaptic dysfunction in the c ontralateral hippocampus. Consequently, we examined the hippocampal th eta rhythm, an EEG pattern thought to be associated with learning. Ini tial comparisons between intact and lesioned rats revealed no obvious differences in basal theta rhythm properties. However, manipulations o f ascending brainstem projections to hippocampus with drugs specific f or serotonergic, noradrenergic and cholinergic receptors uncovered dif ferences. Antagonism of 5-HT3 receptors known to promote learning sign ificantly increased theta frequency in controls and adult lesioned rat s, but not after neonatal damage. In contrast, blockade of noradrenerg ic-alpha(2) receptors had no effect. Antagonism of cholinergic recepto rs which typically impairs learning disrupted theta and caused irregul ar, high-amplitude activity that was significantly more pronounced in the lesioned groups. A final approach involved pharmacological facilit ation of AMPA receptor-mediated currents, using a drug which enhances memory. This treatment significantly enhanced theta frequency in contr ols and animals lesioned as adults. In contrast, it failed to do so in rats lesioned at birth. These observations suggest that latent dysfun ction in contralateral hippocampal physiology may contribute to the la sting memory deficits seen after unilateral hippocampal lesion in neon ates. (C) 1997 Elsevier Science B.V.