H. Vanpraag et al., NEONATAL VS. ADULT UNILATERAL HIPPOCAMPAL-LESIONS - DIFFERENTIAL ALTERATIONS IN CONTRALATERAL HIPPOCAMPAL THETA-RHYTHM, Brain research, 768(1-2), 1997, pp. 233-241
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.