TRKA ACTIVATION IS SUFFICIENT TO RESCUE AXOTOMIZED CHOLINERGIC NEURONS

To test the molecular nature of the NGF receptor responsible for the a bility of NGF to rescue septal cholinergic neurons following axotomy, we infused polyclonal antibodies that act as specific agonists of trkA (RTA) into the lateral ventricle of fimbria-fornix lesioned animals. Rats receiving chronic intraventricular infusions of RTA showed signif icantly more low affinity NGF receptor immunoreactive (p75(NGFR-IR)) n eurons on the lesioned side than did control animals 2 weeks following unilateral fimbria-fornix lesion. RTA also initiated cholinergic spro uting. Infusions of RTA in combination with an antibody that blocks p7 5(NGFR) (REX) did not reduce the cell savings effect observed with RTA alone. However, animals infused with RTA plus REX demonstrated signif icantly less sprouting. These findings suggest that antibody-induced t rkA activation is sufficient to mediate NGF-promoted survival of axoto mized cholinergic neurons in vivo.