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

Long-chain PUFA supplementation in rural African infants: a randomized controlled trial of effects on gut integrity, growth, and cognitive development.

BACKGROUND: Intestinal damage and malabsorption caused by chronic environmental enteropathy are associated with growth faltering seen in infants in less-developed countries. Evidence has suggested that supplementary omega-3 (n-3) long-chain PUFAs (LC-PUFAs) might ameliorate this damage by reducing gastrointestinal inflammation. LC-PUFA supplementation may also benefit cognitive development. OBJECTIVE: We tested whether early n-3 LC-PUFA supplementation improves infant intestinal integrity, growth, and cognitive function. DESIGN: A randomized, double-blind, controlled trial [200 mg DHA and 300 mg EPA or 2 mL olive oil/d for 6 mo] was conducted in a population of 172 rural Gambian infants aged 3-9 mo. The primary endpoints were anthropometric measures and gut integrity [assessed by using urinary lactulose:mannitol ratios (LMRs)]. Plasma fatty acid status, intestinal mucosal inflammation (fecal calprotectin), daily morbidity, and cognitive development (2-step means-end test and an attention assessment) were secondary endpoints. RESULTS: PUFA supplementation resulted in a significant increase in plasma n-3 LC-PUFA concentrations (P < 0.001 for both DHA and EPA) and midupper arm circumference (MUAC) (effect size: 0.31 z scores; 95% CI: 0.06, 0.56; P = 0.017) at 9 mo of age. At 12 mo, MUAC remained greater in the intervention group, and we observed significant increases in skinfold thicknesses (P ≤ 0.022 for all). No other significant differences between treatment groups were detected for growth or LMRs at 9 mo or for secondary outcomes. CONCLUSIONS: Fish-oil supplementation successfully increased plasma n-3 fatty acid status. However, in young, breastfed Gambian infants, the intervention failed to improve linear growth, intestinal integrity, morbidity, or selected measures of cognitive development. The trial was registered at www.isrctn.org as ISRCTN66645725