Infusion of nerve growth factor (NGF) into kitten visual cortex increases immunoreactivity for NGF, NGF receptors, and choline acetyltransferase in basal forebrain without affecting ocular dominance plasticity or column development

Abstract

AbstractöIntracerebroventricular or intracortical administration of nerve growth factor (NGF) has been shown to block or attenuate visual cortical plasticity in the rat. In cats and ferrets, the e¡ects of exogenous NGF on development and plasticity of visual cortex have been reported to be small or nonexistent. To determine whether locally delivered NGF a¡ects ocular dominance column formation or the plasticity produced by monocular deprivation in cats at the height of the critical period, we infused recombinant human NGF into the primary visual cortex of kittens using an implanted cannula minipump. NGF had no e¡ect on the normal developmental segregation of geniculocortical a¡erents into ocular dominance columns as determined both physiologically and anatomically. The plasticity of binocular visual cortical responses induced by monocular deprivation was also normal in regions of immunohistochemically detectable NGF infusion, as measured using intrinsic signal optical imaging and single-unit electrophysiology. Immunohistochemical analysis of the basal forebrain regions of the same animals demonstrated that the NGF infused into cortex was biologically active, producing an increase in the number of NGF-, TrkA-, p75 NTR -, and choline acetyltransferase-positive neurons in basal forebrain nuclei in the hemisphere ipsilateral to the NGF minipump compared to the contralateral basal forebrain neurons.We conclude that NGF delivered locally to axon terminals of cholinergic basal forebrain neurons resulted in increases in protein expression at the cell body through retrograde signaling. ß 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.Key words: TrkA, p75, choline acetyltransferase, retrograde transport, acetylcholine, monocular deprivation.Monocular deprivation (MD) is a well-studied model of experience-dependent cortical plasticity. When one eye of an animal is occluded during a critical period of development, that eye loses most of its ability to drive neurons in primary visual cortex, shifting the distribution of visual responses to favor the nondeprived eye (Wiesel and Hubel, 1963). Intracerebroventricular (ICV) administration of the neurotrophin nerve growth factor (NGF) to rats during a critical period of development blocks the e¡ects of MD (Domenici et al., 1991;Ma¡ei et al., 1992). This has been demonstrated at several levels of analysis, including physiological, anatomical, immunocytochemical, and behavioral (for a review, see Cellerino and Ma¡ei, 1996). Infusion of NGF directly into developing rat visual cortex also prevents physiological ocular dominance plasticity (Lodovichi et al., 2000).In addition, anti-NGF antibodies prevent normal anatomical and physiological development of the visual system when they are administered to rats by implantation of antibody-secreting hybridoma cells in the lateral ventricle (Berardi et al., 1994). These antibodies also prolong the critical period for ocular dominance plasticity in the rat (Domenici et al., 1994a). Together, these results demonstrate an imp...

Stimulation of the Nucleus Basalis of Meynert Produces an Increase in the Extracellular Release of Nerve Growth Factor in the Rat Cerebral Cortex

“…In addition, cells labeled with the retrograde tracer, fluorogold, in the NBM after injection of the tracer into the cortex ipsilateral to the anti-NGF injection site are reduced compared to controls, indicating a disruption in the connectivity between the cortex and the basal forebrain. Based on the above mentioned previous studies [12,13,16,29] and our present results, activation of the NBM may help to maintain neuronal organization in both the target region of NBM axons and the NBM itself due to an increase in NGF release into the cortical extracellular fluid. The present findings may be relevant for understanding the pathogenic mechanisms of neuronal degeneration in the NBM and atrophy of the cerebral cortex in Alzheimer's disease.…”

“…For example, NGF infused into the cerebral cortex increases the number of NGF-and choline acetyltransferase-positive neurons in the kitten basal forebrain nuclei ipsilateral to the NGF infusion [29]. Furthermore, local injections of anti-NGF antibodies into the cortex of the adult rat induced a dramatic reduction of cortical acetylcholine release after high KCl stimulation [16].…”

Role of NGF in Neuronal Plasticity in the Lateral Reticular Nucleus in Chronic Inflammatory Pain

“…Therefore, we hypothesize that NGF synthesis is increased in the LRt, captured and retrogradely transported by spinoreticular neurons to their cell bodies in the deep layers of the spinal cord in this model of sustained inflammatory pain. As previously described in cortical neurons [39,40], increased NGF content could enhance TrkA synthesis and might explain the increased TrkA-IR described in our previous article [16].…”

Cholinergic Abnormalities, Endosomal Alterations and Up-Regulation of Nerve Growth Factor Signaling in Niemann-Pick Type C Disease

“…We also observed increased ChAT levels in MS homogenates from NPC1-/- mice compared to WT mice (Figure 2E). Because chat is under the control of NGF signaling, these results suggest an increased response to endogenous NGF [47,48]. Finally, to determine whether axotomized MS cholinergic neurons in NPC1 -/- mice respond to NGF in vivo, we infused WT and NPC1 -/- mouse brains with NGF for 7 days starting after the surgery.…”