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, antagonists, or excitotoxic lesions of the basal forebrain may not be reflective entirely of changes in cholinergic tone, in so far as these interventions also involve noncholinergic neurons. We examined electrocortical activity in rats following bilateral intracerebroventricular administration of 192 IgG-saporin (1.8 microg/ventricle), a selective cholinergic immunotoxin directed to the low-affinity nerve growth factor receptor p75. The immunotoxin resulted in extensive loss of choline acetyl transferase (ChAT) activity in neocortex (80%-84%) and hippocampus (93%), with relative sparing of entorhinal-piriform cortex (42%) and amygdala (28%). Electrocortical activity demonstrated modest increases in 1- to 4-Hz power, decreases in 20- to 44-Hz power, and decreases in 4- to 8-Hz intra- and interhemispheric coherence. Rhythmic slow activity (RSA) occurred robustly in toxin-treated animals during voluntary movement and in response to physostigmine, with no significant differences seen in power and peak frequency in comparison with controls. Physostigmine significantly increased intrahemispheric coherence in lesioned and intact animals, with minor increases seen in interhemispheric coherence. Our study suggests that: (1) electrocortical changes in response to selective cholinergic deafferentation are more modest than those previously reported following excitotoxic lesions; (2) changes in cholinergic tone affect primarily brain electrical transmission within, in contrast to between hemispheres; and (3) a substantial cholinergic reserve remains following administration of 192 IgG-saporin, despite dramatic losses of ChAT in cortex and hippocampus. Persistence of a cholinergically modulated RSA suggests that such activity may be mediated through cholinergic neurons which, because they lack the p75 receptor, remain unaffected by the immunotoxin.
Holschneider
D P
DP
Department of Neurology, University of Southern California, School of Medicine, Los Angeles, USA. holschne@hsc.usc.edu
Waite
J J
JJ
Leuchter
A F
AF
Walton
N Y
NY
Scremin
O U
OU
D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018678:Cholinergic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004569:Electroencephalography / Q000187:drug effects; D018728:Entorhinal Cortex / Q000187:drug effects / Q000502:physiology; D007839:Functional Laterality; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D000922:Immunotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D009699:N-Glycosyl Hydrolases; D019579:Neocortex / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009928:Organ Specificity; D010830:Physostigmine / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins
C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D018678:Cholinergic Agents; D000922:Immunotoxins; D054789:Ribosome Inactivating Proteins, Type 1; D010830:Physostigmine; D002795:Choline O-Acetyltransferase; D009699:N-Glycosyl Hydrolases; D000076985:Saporins