Conclusions

The results reported in this chapter show that visual experience and neurotrophins cooperate in guiding the development of vision. The actions of neurotrophins and electrical activity are linked in a functional chain which is often reciprocal: activity affects neurotrophin production and uptake, neurotrophins regulate synaptic transmission and may affect electrical activity in visual cortical neurons; visual experience is not sufficient to drive visual cortical development if endogenous neurotrophin action is antagonized, and exogenous neurotrophins become uneffective if electrical activity is blocked. At the other end, neurotrophins seem to be able to promote visual development even in the absence of visual experience, as suggested by the experiments with dark-reared animals.

The neurotrophins active in visual cortical development and plasticity—BDNF, NT4, and NGF—seem to play their roles by acting on different targets: each neurotrophin has its particular subset of targets among the intracortical neurons and the cortical afferents. Some targets are direct, as with the inhibitory circuitry and the neurotrophins BDNF and NT4; some are indirect, in that the action of the neu-rotrophin is mediated by a neuromodulatory system, such as the cholinergic system. The possible sites of action of neu-rotrophins in visual cortical plasticity are sketched in Figure 4.10. It is evident that neurotrophin action is not limited to thalamic afferents but involves both cortical circuitry and subcortical afferents.

Figure 4.10. Possible sites of action of neurotrophins on visual cortical plasticity. Synergistic and antagonistic effects of neu-rotrophins, however clearly possible, are not included in the model. Even so, it is clear that several neural circuits are involved. Some targets of neurotrophin action could be common, such as the basal thalamic afferents

Figure 4.10. Possible sites of action of neurotrophins on visual cortical plasticity. Synergistic and antagonistic effects of neu-rotrophins, however clearly possible, are not included in the model. Even so, it is clear that several neural circuits are involved. Some targets of neurotrophin action could be common, such as the basal forebrain cholinergic neurons or the intracortical excitatory circuitry. Some could be specific targets for specific neurotrophins; for instance, NT4 seems to be most effective on thalamic afferents, and BDNF/NT4 seem to be specifically active on inhibitory intracor-tical circuitry.

Up to 10 years ago, neurotrophins were known for their involvement in survival, differentiation, and maintenance of specific classes of neurons in the PNS. Now the scenario has completely changed, and their involvement is at least equally prominent in the CNS. In the CNS, however, neurotrophins are not survival factors for neurons, but rather survival factors for neural connections. In the developing CNS, neu-rotrophins are essential for the formation, maintenance, and plasticity of synaptic contacts and are crucial for the development of sensory functions. In adult life, they are likely to be still at work in the control of cortical plasticity, and modifications of their activity could be responsible for the slow decline of cognitive functions with age.

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