Nerve growth factor (NGF) prevents the shift in ocular dominance distribution of visual cortical neurons in monocularly deprived rats

Abstract

The hypothesis that NGF could play a role in the plasticity of the developing mammalian visual cortex was tested in monocularly deprived (MD) rats. In particular, we have asked whether an exogenous supply of NGF could prevent the changes in ocular dominance distribution induced by monocular deprivation. Hooded rats were monocularly deprived for 1 month, starting at postnatal day 14 (P14), immediately before eye opening, by means of eyelid suture. In eight rats, only monocular deprivation was performed; in eight rats, monocular deprivation was combined with intraventricular injections of beta-NGF, and in three rats, with intraventricular injections of cytochrome C. Injections (2 microliters) were given every other day for a period of 1 month. Single neuron activity was recorded in the primary visual cortex of MD rats, MD rats treated with NGF, and MD rats treated with cytochrome C at the end of the deprivation period, and in normal rats of the same age. We found that monocular deprivation caused a striking change in the ocular dominance distribution of untreated MD rats, reducing binocular cells by a factor of two and increasing by a factor of eight the number of cells dominated by the nondeprived eye. In MD NGF-treated rats, the ocular dominance distribution was indistinguishable from the normal. Cytochrome C treatment was completely ineffective in preventing the ocular dominance shift induced by monocular deprivation. To test whether NGF affected cortical physiology or interfered with transmission of visual information, we evaluated in NGF-treated rats the spontaneous discharge and the orientation selectivity. We found these functional properties to be in the normal range. We conclude that NGF is effective in preventing the effects of monocular deprivation in the rat visual cortex and suggest that NGF is a crucial factor in the competitive processes leading to the stabilization of functional geniculocortical connections during the critical period.

Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system

“…Blocking the input from one eye leads to the shrinkage of the corresponding neuronal cell bodies and axons in the lateral geniculate nucleus, and the input from the nondeprived eye takes over. Early experiments with NGF in the rat indicated that the consequences of monocular deprivation can be prevented by the administration of NGF (Maffei et al 1992). Conversely, NGF-antibodies prevent normal visual system development (Berardi et al 1994).…”

Nerve growth factor as a paradigm of neurotrophins related to Alzheimer's disease

“…Although NGF perfusion in hippocampal slices (Tancredi et al, 1993) has been reported to block the long-term potentiation (LTP) appearance, other papers have shown no NGF effects on hippocampal and visual cortex plasticity (Khang and Schuman, 1995;Figurov et al, 1996;Akaneya et al, 1997) Moreover, local TrkA activation in primary visual cortex (Pizzorusso et al, 1999) and in vivo NGF injection into the lateral ventricles (Maffei et al, 1992;Lodovichi et al, 2000) counteract the ocular dominance distribution of visual cortical neurons in monocularly deprivated rats. In addition, the blockage of endogenous NGF also interferes with the rat visual system maturation by influencing the critical period Domenici et al, 1994) and exogenous NGF supply favors longterm depression (LTD) over LTP in visual cortical layer II-III of 16 to 18-day-old rats (Pesavento et al, 2000;Brancucci et al, 2004).…”

Different Mechanisms for Loss and Recovery of Binocularity in the Visual Cortex

“…Recent cDNA array analysis has shown that several clusters of genes may be involved in visual cortical plasticity (Prasad et al, 2002). Some specific molecules include NMDA receptors (Bear et al, 1990;Rauschecker et al, 1990;Roberts et al, 1998), neurotrophins (Maffei et al, 1992;Galuske et al, 2000;Gillespie et al, 2000), and protein kinase A (Beaver et al, 2001). A common mechanism through which these molecules might act in ocular dominance plasticity is phosphorylation of the cAMP/ Ca 2ϩ response element-binding protein (CREB), which in turn regulates the transcription of plasticity-related genes (Gonzalez and Montminy, 1989;Deisseroth et al, 1996;Finkbeiner et al, 1997).…”