RT Journal Article
SR Electronic
T1 Learning Impairment and Cholinergic Deafferentation after Cortical Nerve Growth Factor Deprivation
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3796
OP 3803
DO 10.1523/JNEUROSCI.17-10-03796.1997
VO 17
IS 10
A1 Humberto Gutiérrez
A1 Marı́a Isabel Miranda
A1 Federico Bermúdez-Rattoni
YR 1997
UL http://www.jneurosci.org/content/17/10/3796.abstract
AB 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 vivomicrodialysis 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.