Changes in electrocortical power and coherence in response to the selective cholinergic immunotoxin 192 IgG-saporin

Changes:in brain electrical activity in response to cholinergic agonists, a ntagonists, or excitotoxic lesions of the basal forebrain may not be reflec tive entirely of changes in cholinergic tone, in so far as these interventi ons also involve noncholinergic neurons. We examined electrocortical activi ty in rats following bilateral intracerebroventricular administration of 19 2 IgG-saporin (1.8 mu g/ventricle), a selective cholinergic immunotoxin dir ected to the low-affinity nerve growth factor receptor p75. The immunotoxin resulted in extensive loss of choline acetyl transferase (ChAT) activity i n neocortex (80%-84%) and hippocampus (93%), with relative sparing of entor hinal-piriform cortex (42%) and amygdala (28%). Electrocortical activity de monstrated modest increases in 1- to 4-Hz power, decreases in 20- to 44-Hz power, and decreases in 4- to 8-Hz intra- and in- terhemispheric coherence. Rhythmic slow activity (RSA) occurred robustly in toxin-treated animals du ring voluntary movement and in response to physostigmine, with no significa nt differences seen in power and peak frequency in comparison with controls . Physostigmine significantly increased intrahemispheric coherence in lesio ned and intact animals, with minor increases seen in interhemispheric coher ence. Our study suggests that: (1) electrocortical changes in response to s elective cholinergic deafferentation are more modest than those previously reported following excitotoxic lesions; (2) changes in cholinergic tone aff ect primarily brain electrical transmission within, in contrast to between hemispheres; and (3) a substantial cholinergic reserve remains following ad ministration of 192 IgG-saporin, despite dramatic losses of ChAT in cortex and hippocampus. Persistence of a cholinergically modulated RSA suggests th at such activity may be mediated through cholinergic neurons which, because they lack the p75 receptor, remain unaffected by the immunotoxin.