BRAIN-DERIVED NEUROTROPHIC FACTOR REVERSES EXPERIENCE-DEPENDENT SYNAPTIC MODIFICATIONS IN KITTEN VISUAL-CORTEX

During a critical period of early postnatal development the functional architecture of the visual cortex is shaped by experience-dependent c ircuit selection following a Hebbian mechanism. One consequence is tha t monocular deprivation (MD) leads to competitive repression of the in put from the deprived eye. Recently it has been proposed that this pro cess might involve activity-dependent competition for neurotrophic sub stances because the synthesis of brain-derived neurotrophic factor (BD NF) is regulated by visual input. Here we investigate the effects of i ntracortical infusion of BDNF and nerve growth factor (NGF) on MD effe cts in the visual cortex. Neuronal responses were monitored with optic al and single-unit recording techniques in the visual cortex of kitten s that had been infused intracortically either with BDNF, NGF or cytoc hrome C while subjected to MD for 1 week during the peak of the critic al period, NGF or cytochrome C had no effect on the consequences of MD . After BDNF treatment, by contrast, ocular dominance (OD) shifted tow ards the deprived eye in a zone extending 2.5-3.5 mm from the infusion cannula, and neurons lost their orientation selectivity. At intermedi ate distances both eyes activated the cortex equally well and response s were again tuned for orientation; at still larger distances OD was s hifted towards the normal eye. Thus, BDNF antagonizes the functional e ffects of MD and at high concentrations causes paradoxical disconnecti on of non-deprived afferents and a loss of orientation selectivity.