[Glutamate signaling and neural plasticity].
Proper functioning of the nervous system relies on the precise formation of neural circuits during development. At birth, neurons have redundant synaptic connections not only to their proper targets but also to other neighboring cells. Then, functional neural circuits are formed during early postnatal development by the selective strengthening of necessary synapses and weakening of surplus connections. Synaptic connections are also modified so that projection fields of active afferents expand at the expense of lesser ones. We have studied the molecular mechanisms underlying these activity-dependent prunings and the plasticity of synaptic circuitry using gene-engineered mice defective in the glutamatergic signaling system. NMDA-type glutamate receptors are critically involved in the establishment of the somatosensory pathway ascending from the brainstem trigeminal nucleus to the somatosensory cortex. Without NMDA receptors, whisker-related patterning fails to develop, whereas lesion-induced plasticity occurs normally during the critical period. In contrast, mice lacking the glutamate transporters GLAST or GLT1 are selectively impaired in the lesion-induced critical plasticity of cortical barrels, although whisker-related patterning itself develops normally. In the developing cerebellum, multiple climbing fibers initially innervating given Purkinje cells are eliminated one by one until mono-innervation is achieved. In this pruning process, P/Q-type Ca2+ channels expressed on Purkinje cells are critically involved by the selective strengthening of single main climbing fibers against other lesser afferents. Therefore, the activation of glutamate receptors that leads to an activity-dependent increase in the intracellular Ca2+ concentration plays a key role in the pruning of immature synaptic circuits into functional circuits. On the other hand, glutamate transporters appear to control activity-dependent plasticity among afferent fields, presumably through adjusting extracellular glutamate concentrations to optimally reflect their different neural activities in postsynaptic target neurons. Thus, armed with both molecular mechanisms, functional neural circuits develop and mature during the early postnatal period.
Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido. watamasa@med.hokudai.ac.jp
Masahiko
M
Watanabe
D027322:Amino Acid Transport System X-AG / Q000378:metabolism; D000818:Animals; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D011689:Purkinje Cells / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction
D027322:Amino Acid Transport System X-AG; D018698:Glutamic Acid