That docosahexaenoic acid (DHA), an omega–3 polyunsaturated fatty acid (PUFA), can affect brain function and behavior no longer is controversial: deficiencies in this compound are associated with impairments in cognitive development, correctable by its repletion [1] and the consumption of DHA or fish oil by humans reportedly slows cognitive decline in the aged [2] and in subjects with early Alzheimer’s disease[3] and promotes mental development in infants [4]. Some of DHA’s effects on brain have been shown to occur with ‘physiologic’ doses which raise its plasma concentrations significantly but keep them within their normal range [5]; others probably are pharmacologic. Some are shared with eicosapentaenoic acid (EPA), another omega–3 PUFA, or with the omega–6 fatty acid arachidonic acid (AA), and others with both or neither of these compounds.

In general, nutrients and drugs that modify brain function or behavior tend to do so by affecting synaptic transmission [6]: they modulate the quantities of particular neurotransmitter molecules within synaptic clefts, or act directly on the transmitter’s receptors or on downstream signal-transduction molecules. Is this also the case for DHA?

Hypotheses attempting to explain how DHA affectsbrain function have, in general, been based on its incorporation into membrane phospholipids and consequent effects on membrane fluidity [7]; on proteins affecting transcription (RXR [8]) or neurite outgrowth (syntaxin-3 [9]); on increasing phosphatidylserine (PS) production [10]; on suppression of neuronal apoptosis [11]; or on the neuroprotective actions of its product 10,17S-docosatriene [12]. Little has been known concerning possible changes DHA might produce in synaptic transmission.