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Volume 17, Number 10, Issue of May 15, 1997 pp. 3796-3803
Copyright ©1997 Society for Neuroscience

Learning Impairment and Cholinergic Deafferentation after Cortical Nerve Growth Factor Deprivation

Received Nov. 18, 1996; revised Feb. 14, 1997; accepted Feb. 21, 1997.

Humberto Gutiérrez, María Isabel Miranda, and Federico Bermúdez-Rattoni

Departamento de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 Mexico D. F., Mexico

Cholinergic basal forebrain (CBF ) neurons have been shown to respond in vivo 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 in CNS neurons. To test directly whether cortically derived NGF is functionally required for the cholinergic functions mediated by the cerebral cortex, repeated injections of anti-NGF mAbs were locally applied into the insular cortex (IC) of rats. The biochemical results, using an in vivo microdialysis technique, showed a dramatic lack of extracellular release of acetylcholine after high potassium stimulation compared with controls. Furthermore, by using small injections of the neurotracer fluorogold, we found a corresponding disruption in the connectivity between the IC and the CBF. Behavioral experiments showed that the NGF 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 aversion when the conditioning trial was established before injections of NGF antibodies. Given these results, it seems that cortical cholinergic functions are actively dependent on locally derived NGF in the adult normal brain, and that the cholinergic activity from the CBF is not necessary for recalling aversive stimuli, but is necessary for the acquisition of aversively motivated conditionings.

Key words: inhibitory avoidance; conditioned taste aversion; anti-NGF antibodies; memory; cholinergic basal forebrain; cortical cholinergic activity

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