Experience-Dependent Plasticity and the Maturation of Glutamatergic Synapses

Together, these observations suggest the following general hypothesis: during early development, neural networks are established by genetically specified cues and activity-dependent processes. Glutamatergic synapses that form during this period display a rapid, activity-dependent maturation of NMDA and AMPA receptor currents, so that by the time basic networks have been established, glutamatergic pharmacology is much like that observed in the adult. Subsequently, there occurs an extended, late period of development during which established networks are modified by experience, in part through the formation and selective stabilization of novel glutamatergic synapses. These novel synapses are created initially as either synapses with long-duration NMDA receptor currents and/or as silent, purely NMDAergic synapses, recapitulating the maturation of glutamatergic synaptic currents in early development. In either case, the high NMDA/AMPA current ratio of such synapses would be beneficial in enabling rapid activity-dependent adjustment of synaptic strength by NMDA receptor-dependent mechanisms (Katz and Shatz 1996xSynaptic activity and the construction of cortical circuits. Katz, L.C and Shatz, C.J. Science. 1996; 274: 1133–1138Crossref | PubMed | Scopus (1909)See all ReferencesKatz and Shatz 1996). If novel synapses were formed as silent synapses, an additional advantage would be gained: because synapses would be made functional only if they were appropriately targeted, the presence of inappropriate synapses would not adversely affect the performance of the preexisting circuit (Cline et al. 1996xIn vivo development of neuronal structure and function. Cline, H.T, Wu, G.-Y, and Malinow, R. Cold Spring Harbor Symp. Quant. Biol. 1996; 61: 95–104Crossref | PubMedSee all ReferencesCline et al. 1996). Thus, large-scale adaptive adjustments could be made, for example, by nondirected axonal outgrowth and synapse formation, followed by the selective activation of appropriate synapses. In this model, network optimization could proceed without jeopardizing normal function, an essential feature if plasticity is to occur in a circuit that is necessary for the survival of the animal. This is certainly the case for the barn owl, in which ICX plasticity takes place at an age when juvenile owls have left the nest and depend on sound localization to find their prey. Finally, by the end of the late developmental period, which coincides with sexual maturation, the capacity for synaptogenesis is dramatically restricted, reducing the ability of many networks to adapt to novel changes in sensory or motor experience. Within the juvenile period, this restriction may occur earlier for low order networks and at progressively later ages for high order networks (Fox and Zahs 1994xCritical period control in sensory cortex. Fox, K and Zahs, K. Curr. Opin. Neurobiol. 1994; 4: 112–119Crossref | PubMed | Scopus (57)See all ReferencesFox and Zahs 1994).A prediction of this model is that, except for brain regions in which the capacity for synaptogenesis persists throughout life, experience-dependent changes in neural circuits in the adult will be mediated primarily through changes in the efficacy of the synapses that exist at the end of the juvenile period. Thus, experience during the juvenile period may be critical in establishing the repertoire of connectional states available to the adult nervous system (Knudsen 1998xCapacity for plasticity in the adult owl auditory system expanded by juvenile experience. Knudsen, E.I. Science. 1998; 279: 1531–1533Crossref | PubMed | Scopus (100)See all ReferencesKnudsen 1998).*Present address: Department of Psychiatry, Langley Porter Psychiatric Institute, Box 0984, University of California, San Francisco, California 94143.