The tractable contribution of synapses and their component molecules to individual differences in learning

Though once of central importance to psychologists and neurophysiologists a like, the elucidation of neural substrates for individual differences in le arning no longer attracts a broad research effort and occupies a place of l argely historical interest to the contemporary disciplines. The decline in interest in this subject ensued in part from the perception, arrived at dec ades ago, that individual differences in learning were not quantified as ea sily as had once been presumed. Furthermore, the dominant hypotheses in the field defied testing within the constraints imposed by the complex and lar gely inaccessible vertebrate nervous system. Using a 'model systems' approa ch where the individual cells and synaptic interactions that comprise a neu ral network can be identified, we have returned to this question and have e stablished a framework by which we can begin to discern the basis for much of the variability between individuals in their capacity to learn. In the m arine mollusc Hermissenda, we have found that a common influence on transmi tter exocytosis is expressed homogeneously throughout the nervous system re gardless of transmitter system or receptor class. Though uniformly expresse d within an individual, this influence on synaptic efficacy is differential ly expressed between animals. Importantly, the basal efficiency of exocytos is expressed in an individual nervous system is strongly correlated with th e degree to which activity-dependent forms of neuronal/synaptic facilitatio n can be induced in that nervous system, and predicts the capacity for the intact animal to learn a Pavlovian association. Furthermore, we have establ ished that a decline in basal synaptic efficacy in aged animals, arising fr om chronic presynaptic Ca2+ 'leak', may contribute to age-related learning impairments. Because certain fundamental components of the exocytotic casca de are conserved widely across cell types, transmitter systems and species, the principles that we describe may have broad implications for understand ing normal variability in learning, but also, in the development of specifi c strategies to compensate for mild learning deficits and age-related cogni tive decline. (C) 2000 Elsevier Science B.V. All rights reserved.