Ubiquitous molecular substrates for associative learning and activity-dependent neuronal facilitation.

Recent evidence suggests that many of the molecular cascades and substrates that contribute to learning-related forms of neuronal plasticity may be conserved across ostensibly disparate model systems. Notably, the facilitation of neuronal excitability and synaptic transmission that contribute to associative learning in Aplysia and Hermissenda, as well as associative LTP in hippocampal CA1 cells, all require (or are enhanced by) the convergence of a transient elevation in intracellular Ca2+ with transmitter binding to metabotropic cell-surface receptors. This temporal convergence of Ca2+ and G-protein-stimulated second-messenger cascades synergistically stimulates several classes of serine/threonine protein kinases, which in turn modulate receptor function or cell excitability through the phosphorylation of ion channels. We present a summary of the biophysical and molecular constituents of neuronal and synaptic facilitation in each of these three model systems. Although specific components of the underlying molecular cascades differ across these three systems, fundamental aspects of these cascades are widely conserved, leading to the conclusion that the conceptual semblance of these superficially disparate systems is far greater than is generally acknowledged. We suggest that the elucidation of mechanistic similarities between different systems will ultimately fulfill the goal of the model systems approach, that is, the description of critical and ubiquitous features of neuronal and synaptic events that contribute to memory induction

Mechanisms of neurotoxicity and their relationship to behavioural changes

In this review some of the evidence relating behavioral alterations induced by 2 neurotoxic chemicals, lead acetate and methyl mercury is presented with an attempt to relate these changes to the underlying neurobiological mechanisms. In the case of neonatal lead poisoning, the results of the early behavioral studies were confounded by excessive lead concentrations resulting in undernutrition of the pups. Subsequent studies in both rodents and monkeys have shown that blood-lead concentrations comparable to those seen in children can induce behavioral alterations that may be related to hippocampal damage. In the case of methyl mercury which is a potent cytotoxic agent, prenatal exposure results in widespread cortical, and cerebellar alterations characterized by reduced myelination, delayed migration and loss of neurons. These morphological alterations are accompanied by permanent alterations in learning and memory as well as altered pharmacological sensitivity in catecholaminergic systems. Recommendations are made for better formulated behavioral and neurobiological assays in neurotoxicology in order to lead to a better understanding of the toxicity of chemicals