Prenatal availability of choline modifies development of the hippocampal cholinergic system.

Abstract

Choline supplementation during fetal development [embryonic days (E) 11-17] permanently enhances memory performance in rats. To characterize the neurochemical mechanisms that may mediate this effect, we investigated the development of indices of the cholinergic system in the hippocampus: choline acetyltransferase (ChAT), acetylcholinesterase (AChE), synthesis of acetylcholine (ACh) from choline transported by high-affinity choline uptake (HACU), and potassium-evoked ACh release. During E11-E17, Sprague-Dawley pregnant rats consumed 0 [choline-deficient (ChD)], 1.3 [control (ChC)], and 4.6 [choline-supplemented (ChS)] mmol/(kg x day) of choline, respectively. On postnatal days 17 and 27, hippocampi of the ChD animals had the highest AChE and ChAT activities, and increased synthesis of ACh from choline transported by HACU, concomitant with reductions of tissue ACh content relative to the ChC and ChS rats and an inability to sustain depolarization-evoked ACh release relative to the ChS animals. In contrast, AChE and ChAT activities, and ACh synthesized from choline transported by HACU, were lowest in ChS rats whereas depolarization-evoked ACh release was the highest. This pattern of changes suggests that the hippocampus of the ChD animals is characterized by fast ACh recycling and efficient choline reutilization for ACh synthesis, presumably to maintain adequate ACh release despite the decrease of the ACh pool, whereas in the ChS animals ACh turnover and choline recycling is slower while the evoked release of ACh is high. Together, the data show a complex adaptive response of the hippocampal cholinergic system to prenatal choline availability and provide a novel example of developmental plasticity in the nervous system governed by the supply of a single nutrient.