LEARNING IMPAIRMENT AND CHOLINERGIC DEAFFERENTATION AFTER CORTICAL NERVE GROWTH-FACTOR DEPRIVATION

Cholinergic basal forebrain (CBF) neurons have been shown to respond i n vive to exogenous administration of NGF. Although neurotrophins and their receptors are widely expressed in the CNS, little data exist for the physiological significance of endogenous neurotrophin signaling i n CNS neurons. To test directly whether cortically derived NGF is func tionally required for the cholinergic functions mediated by the cerebr al cortex, repeated injections of anti-NGF mAbs were locally applied i nto the insular cortex (IC) of rats. The biochemical results, using an in vivo microdialysis technique, showed a dramatic lack of extracellu ar release of acetylcholine after high potassium stimulation compared with controls. Furthermore, by using small injections of the neurotrac er fluorogold, we found a corresponding disruption in the connectivity between the IC and the CBF. Behavioral experiments showed that the NG F antibodies applied into the IC produced a significant disruption on the acquisition of conditioned taste aversion and inhibitory avoidance learning. However, the same animals were able to recall the taste ave rsion when the conditioning trial was established before injections of NGF antibodies. Given these results, it seems that cortical cholinerg ic functions are actively dependent on locally derived NGF in the adul t normal brain, and that the cholinergic activity from the CBF is not necessary for recalling aversive stimuli, but is necessary for the acq uisition of aversively motivated conditionings.