title: Medial septal cholinergic neurons modulate isoflurane anesthesia.
abstract: BACKGROUND
  Cholinergic drugs are known to modulate the response of general anesthesia. However, the sensitivity of isoflurane or other volatile anesthetics after selective lesion of septal cholinergic neurons that project to the hippocampus is not known.
  
  
  METHODS
  Male Long Evans rats had 192 immunoglobulin G-saporin infused into the medial septum (n = 10), in order to selectively lesion cholinergic neurons, whereas control, sham-lesioned rats were infused with saline (n = 12). Two weeks after septal infusion, the hypnotic properties of isoflurane and ketamine were measured using a behavioral endpoint of loss of righting reflex (LORR). Septal lesion was assessed by counting choline acetyltransferase-immunoreactive cells and parvalbumin-immunoreactive cells.
  
  
  RESULTS
  Rats with 192 immunoglobulin G-saporin lesion, as compared with control rats with sham lesion, showed a 85% decrease in choline acetyltransferase-immunoreactive, but not parvalbumin-immunoreactive, neurons in the medial septal area. Lesioned as compared with control rats showed increased isoflurane sensitivity, characterized by a leftward shift of the graph plotting cumulative LORR percent with isoflurane dose. However, lesioned and control rats were not different in their LORR sensitivity to ketamine. When administered with 1.375% isoflurane, LORR induction time was shorter, whereas emergence time was longer, in lesioned as compared with control rats. Hippocampal 62-100 Hz gamma power in the electroencephalogram decreased with isoflurane dose, with a decrease that was greater in lesioned (n = 5) than control rats (n = 5).
  
  
  CONCLUSIONS
  These findings suggest a role of the septal cholinergic neurons in modulating the sensitivity to isoflurane anesthesia, which affects both induction and emergence. The sensitivity of hippocampal gamma power to isoflurane appears to indicate anesthesia (LORR) sensitivity.
authors: From the Department of Physiology and Pharmacology (S.K.T., J.M., L.S.L.) and Program in Neuroscience (L.S.L.), The University of Western Ontario, London, Ontario, Canada.
authors: Siew Kian
authors: SK
authors: Tai
authors: Jingyi
authors: J
authors: Ma
authors: L Stan
authors: LS
authors: Leung
mesh_terms: D000769:Anesthesia, Inhalation; D018685:Anesthetics, Inhalation; D000818:Animals; D000911:Antibodies, Monoclonal; D004305:Dose-Response Relationship, Drug; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects; D007530:Isoflurane; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects*; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D020318:Rats, Long-Evans; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D020665:Septum of Brain / Q000166:cytology / Q000502:physiology*
chemical_list: C085696:192 IgG-saporin; D018685:Anesthetics, Inhalation; D000911:Antibodies, Monoclonal; D018691:Excitatory Amino Acid Antagonists; D054789:Ribosome Inactivating Proteins, Type 1; D007649:Ketamine; D007530:Isoflurane; D000076985:Saporins