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

Though once of central importance to psychologists and neurophysiologists alike, the elucidation of neural substrates for individual differences in learning no longer attracts a broad research effort and occupies a place of largely historical interest to the contemporary disciplines. The decline in interest in this subject ensued in part from the perception, arrived at decades ago, that individual differences in learning were not quantified as easily as had once been presumed. Furthermore, the dominant hypotheses in the field defied testing within the constraints imposed by the complex and largely inaccessible vertebrate nervous system. Using a 'model systems' approach where the individual cells and synaptic interactions that comprise a neural network can be identified, we have returned to this question and have established 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 marine mollusc Hermissenda, we have found that a common influence on transmitter exocytosis is expressed homogeneously throughout the nervous system regardless of transmitter system or receptor class. Though uniformly expressed within an individual, this influence on synaptic efficacy is differentially expressed between animals. Importantly, the basal efficiency of exocytosis expressed in an individual nervous system is strongly correlated with the degree to which activity-dependent forms of neuronal/synaptic facilitation can be induced in that nervous system, and predicts the capacity for the intact animal to learn a Pavlovian association. Furthermore, we have established that a decline in basal synaptic efficacy in aged animals, arising from chronic presynaptic Ca(2+) 'leak', may contribute to age-related learning impairments. Because certain fundamental components of the exocytotic cascade are conserved widely across cell types, transmitter systems and species, the principles that we describe may have broad implications for understanding normal variability in learning, but also, in the development of specific strategies to compensate for mild learning deficits and age-related cognitive decline.