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.
