Sensory experience is capable of modifying neuronal connectivities in the brain, either by enhancing or diminishing the flow of information. Scientists from the Max Planck Institute for Developmental Biology (Tübingen, Germany) report in "Nature Neuroscience" (May 1998) that these two forms of plasticity differ in their molecular machinery.
Sensory experience during early postnatal development is essential for the optimization of neuronal connections in the brain. While genetic information is only sufficient for the development of the coarse pattern of connections between nerve cells, use-dependent modifications lead to the adaptation of neuronal connectivities to the individuals¹ needs. The basic rules for these modifications are that connections which are rarely used are eliminated, and the flow of information along pathways which are regularily used are strengthened by addition of connections. These modifications of brain circuitries are also believed to underly the mechanisms of learning and forgetting in the mature brain.
The developing visual cortex is an excellent model system to study both forms of plasticity. In this structure the information of both eyes converges and thereby allows depth-vision through a comparison of the pictures seen by either eye. As shown by the pioneering studies by Drs. Hubel and Wiesel in the 1970¹s, impairment of vision in one eye in infants leads to a severe loss of connections from this eye to the cortex. This can result in almost complete blindness of the affected eye within a short period of time. During early development, this loss of function can be recovered by restoring vision in the deprived eye, leading to new formation of connections carrying the according information to the cortex.
Christian M. Müller and Claudius B. Griesinger from the Max Planck Institute for Developmental Biology used this model system to address the mechanisms underlying both consequences of brain plasticity (Nature Neuroscience, vol. 1, 1998). They focussed on the putative role of proteases in the remodelling of connections between nerve cells. Recent data from different laboratories has provided evidence that certain proteases are essential for the development of nerve processes, most likely by digesting proteins in the vicinity of the growing structures. By applying inhibitors against different proteases into the cortex, Müller and Griesinger show that the recovery of function after restoration of vision with a formerly deprived eye can be fully abolished. When protease activity is blocked during impairement of vision through one eye, however, the loss of connections proceeds normally. Therefore it is concluded that proteases are neccessary for only one form of plasticity in the brain, namely the gain of function. By using a variety of different inhibitors it is shown that a cascade of two proteases is essential for brain plasticity. These proteases are Œtissue plasminogen activator¹ and Œplasmin¹, both known to be present and important in the cardiovascular system, where they participate in wound healing.
The study has several implications for the understanding of brain development and experience-dependent plasticity in the brain. As interference with the mechanism underlying the improvement of brain function does not affect the loss of function resulting from disuse, it has to be concluded that the two forms of plasticity proceed independently of each other. The essential role of proteases - known to be involved in growth mechanisms of neurons - for the gain of function through experience strongly suggests that the growth of connections between nerve cells underlies the enhancement of information flow through experience. The knowledge of a molecular mechanism being specific for the improvement of brain function might be useful for the development of therapeutic tools to support the long-term strengthening of connectivities in the brain.