COORDINATE EXPRESSION OF THE VESICULAR ACETYLCHOLINE TRANSPORTER AND CHOLINE-ACETYLTRANSFERASE FOLLOWING SEPTOHIPPOCAMPAL PATHWAY LESIONS

The gene for the vesicular acetylcholine transporter (VAChT) was recen tly cloned and found to be located within a 5' noncoding intron of the gene for choline acetyltransferase (ChAT), There appear to be several shared and unique promoters for each gene, suggesting that control of expression of these two genes can be either coordinated or independen t. Two lesions, axotomy and immunotoxin, directed at the well defined septohippocampal cholinergic pathway were used to determine VAChT and ChAT protein expression in the degenerating terminal fields in the hip pocampus and the cell bodies of the medial septum nucleus after injury . Two weeks after lesioning, decreases of up to 90% in VAChT were foun d in the affected hippocampus by immunoblotting and immunocytochemistr y, similar to ChAT activity. The number of VAChT- and ChAT-immunoposit ive neurons in the medial septum decreased by up to 95%, Eight weeks f ollowing axotomy, the number of VAChT- and ChAT-immunopositive neurons had increased to almost 50% in fimbria-fornix-lesioned animals, indic ating coordinate reexpression of both cholinergic markers in recovered neurons. There was no recovery of either VAChT or ChAT immunoreactivi ty after the irreversible immunotoxin lesions. Thus, with use of immun ological techniques, there appears to be coordinate expression of VACh T and ChAT in the septohippocampal pathway following either unilateral fimbria-fornix or bilateral immunotoxin lesion.