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COLCHICINE INDUCED DEAFFERENTATION OF THE HIPPOCAMPUS SELECTIVELY DISRUPTS CHOLINERGIC RHYTHMICAL SLOW WAVE ACTIVITY
Citation:
Gilbert, M. AND G. Peterson. COLCHICINE INDUCED DEAFFERENTATION OF THE HIPPOCAMPUS SELECTIVELY DISRUPTS CHOLINERGIC RHYTHMICAL SLOW WAVE ACTIVITY. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-91/323.
Description:
It has been proposed that hippocampal theta rhythm (RSA)is generated by the cholinergic septo-hippocampal system. Although ablations of the septum or its projections to the hippocampus disrupt hippocampal RSA, such non-selective lesions damage both cholinergic and noncholinergic septo-hippocampal inputs. The present study assesses the effects of a selective septal neurotoxic lesion on hippocampal RSA. olchicine, which has been reported to be selectively toxic to cholinergic neurons in the medial septum, was injected into the right lateral ventricle, and electrodes were implanted bilaterally into the dorsal hippocampus of female rats. Hippocampal electrical activity was recorded 10-14 days later from the ipsilateral (colchicine-treated) and contralateral (control) hemispheres during locomotor activity or immobility. RSA ranging from 6.3 to 8.7 Hz was evoked in both hippocampi during mobility. Following ip administration of an anesthetic dose of urethane, hippocampal RSA at a frequency of 4 Hz could be elicited in the control hemisphere (n=12) of all animals by pinching the tail. RSA was absent in 6 of 9 animals in the colchicine-treated hemisphere. A decrease in the number of choline acetyltransferase (ChAT)- immunoreactive neurons in the medial septum and a depletion of acetylcholinesterase (AChE)- staining in the hippocampus were evident in the hemisphere ipsilateral to colchicine administration. These data support the septal pacemaker hypothesis of hippocampal theta rhythm and further demonstrate the neurotoxic effect of colchicine on septo-hippocampal cholinergic neurons by the induction of a functional alteration.