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

Area of Science:

• Neuroscience
• Neurobiology
• Neurochemistry

Background:

• Most basal forebrain cholinergic neurons (BFCN) in adult rats express the p75 nerve growth factor receptor (NGFr).
• The immunotoxin 192 IgG-saporin (SAP) selectively eliminates NGFr-positive BFCN, mimicking aspects of Alzheimer's disease.
• Nerve growth factor (NGF) has a trophic effect on BFCN, and its modulation of BFCN projections impacts cortico-cortical interactions.

Purpose of the Study:

• To investigate the opposing effects of NGF and SAP on BFCN and their impact on cortical activity.
• To test the hypothesis that alterations in BFCN projections by SAP and NGF produce opposite effects on cortico-cortical interactions.

Main Methods:

• Recording of multiple local field potentials (LFPs) in the rat temporal cortex.
• Application of bispectral analysis to measure phase-coupled frequencies, indicative of resonance.
• Measurement of choline acetyltransferase (ChAT) activity in the septal area to assess BFCN integrity.

Main Results:

• NGF treatment increased ChAT activity by 45% and shifted non-linear coupling frequencies to >70 Hz, suggesting enhanced short-range functional interactions.
• SAP treatment decreased ChAT activity by nearly 40% and increased phase-coupling at low frequencies (<50 Hz), indicating reduced cortico-cortical interaction.
• Bispectral analysis revealed effects of BFCN on cortical activity not detectable by other methods.

Conclusions:

• NGF and SAP exert opposing effects on BFCN integrity and functional cortico-cortical interactions.
• Bispectral analysis is a valuable tool for studying BFCN effects on cortical activity.
• This methodology could be extended to analyze EEG in Alzheimer's disease patients.