Non-linear cortico–cortical interactions modulated by cholinergic afferences from the rat basal forebrain

In the adult rat most of basal forebrain cholinergic neurons (BFCN) express the low-affinity p75 nerve growth factor receptor (NGFr). The immunotoxin 192 IgG-saporin (SAP) provokes a selective loss of NGFr-positive BFCN, somewhat similar to the loss of integrity of BFCN associated with human senile dementia of Alzheimerʹs type, whereas NGF exerts a trophic action on BFCN. Cortico–cortical interactions are modulated by cholinergic projections of BFCN and it is proposed that alterations of these projections by SAP and by NGF produce opposite effects. This hypothesis was tested by recording multiple local field potentials (LFPs) in the rat temporal cortex and applying bispectral analysis to measure phase-coupled frequencies, somewhat analogous to frequencies of resonance. Choline acetyltransferase (ChAT) activity was measured in the septal area in order to assess the effects of the treatments. NGF-treatment increased ChAT activity by 45% and frequencies of non-linear coupling were shifted towards frequencies higher than 70 Hz, thus suggesting the presence of increased functional interactions in the short range. By contrast, SAP provoked a decrease of nearly 40% in ChAT activity and an increase of phase-coupling in the low frequencies (<50 Hz), being interpreted as a decreased functional cortico–cortical interaction. Bispectral analysis revealed features of the effect of BFCN on cortical activity that could not be observed by other means and offers as a valuable tool of study that could be extended to the EEG of Alzheimerʹs patients.