PRENATAL AVAILABILITY OF CHOLINE MODIFIES DEVELOPMENT OF THE HIPPOCAMPAL CHOLINERGIC SYSTEM

Choline supplementation during fetal development [embryonic days (E) 1 1-17] permanently enhances memory performance in rats. To characterize the neurochemical mechanisms that may mediate this effect, we investi gated the development of indices of the cholinergic system in the hipp ocampus: choline acetyltransferase (ChAT), acetylcholinesterase (AChE) , synthesis of acetylcholine (ACh) from choline transported by high-af finity 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 . day) of choline, respectively. On postnatal days 17 and 27, hippo campi of the ChD animals had the highest AChE and ChAT activities, and increased synthesis of ACh from choline transported by HACU, concomit ant with reductions of tissue ACh content relative to the ChC and ChS rats and an inability to sustain depolarization-evoked ACh release rel ative to the ChS animals. In contrast, AChE and ChAT activities, and A Ch synthesized from choline transported by HACU, were lowest in ChS ra ts whereas depolarization-evoked ACh release was the highest. This pat tern of changes suggests that the hippocampus of the ChD animals is ch aracterized 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 hi gh. Together, the data show a complex adaptive response of the hippoca mpal cholinergic system to prenatal choline availability and provide a novel example of developmental plasticity in the nervous system gover ned by the supply of a single nutrient.