Long lasting modifications in the efficacy of synaptic transmission among neurons are thought to be the basic changes that account for complex processes such as learning and memory. Thus, the comprehension of the mechanisms and factors controlling synaptic plasticity is fundamental to understand higher cognitive functions. The aim of the present work was to investigate possible factors modulating synaptic plasticity in the cortex. One likely candidate is the cholinergic system, arising in the basal forebrain (BFB) and projecting to the cortex, whose deficits are known to impair cognitive functions. It has been found that either disruption of cholinergic neurons or blockade of cholinergic transmission impair Long-Term Potentiation (L TP) in rat visual cortex slices. Conversely, activation of the cholinergic receptors has a facilitatory effect in synaptic strengthening. In addition, by using a transgenic mouse expressing an anti-NGF monoclonal antibody, it has been investigated the long-term effects of Nerve-Growth Factor (NGF) deprivation in cholinergic system functionality, for which NGF is known to exert atrophic action. In these mice, it has been observed an impairment of L TP that can be rescued by application of cholino,mimetic drugs. Beside its action as trophic factor, NGF is known to exert a crucial role in the activity-dependent development and plasticity of visual cortex. This observation prompted me to investigate its possible effect as modulator of synaptic plasticity. It has been found that blocking the NGF-TrkA interaction rescues the developmental loss of L TP in the rat visual cortex. In contrast, an increase in the levels of NGF reduces the capability of synapses to be potentiated. Long-Term Depression and bidirectional plasticity are unaffected. These results indicate that both the cholinergic system and NGF are effective regulators of synaptic strength in the visual cortex. Moreover, the evidence that cholinergic antagonist avoids L TP rescue mediated by blockade of NGF-TrkA interaction and that BFB lesion masks the action of NGF on L TP expression suggest that NGF modulates L TP by means of the BFB cholinergic system.
|Titolo:||Modulation of Cortical Synaptic Plasticity by the Cholinergic System and Nerve-Growth Factor|
|Relatore/i esterni:||Domenici, Luciano|
|Data di pubblicazione:||23-mar-2001|
|Appare nelle tipologie:||8.1 PhD thesis|