Perinatal choline deficiency produces abnormal sensory inhibition in Sprague-Dawley rats

Abstract

Adequate choline levels in rodents during gestation have been shown to be critical to several functions, including certain learning and memory functions, when tested at adulthood. Choline is a selective agonist for the alpha7 nicotinic receptor which appears in development before acetylcholine is present. Normal sensory inhibition is dependent, in part, upon sufficient numbers of this receptor in the hippocampus. The present study assessed sensory inhibition in Sprague-Dawley rats gestated on normal (1.1 g/kg), deficient (0 g/kg) or supplemented (5 g/kg) choline in the maternal diet during the critical period for cholinergic cell development (E12-18). Rats gestated on deficient choline showed abnormal sensory inhibition when tested at adulthood, while rats gestated on normal or supplemented choline showed normal sensory inhibition. Assessment of hippocampal alpha-bungarotoxin to visualize nicotinic alpha7 receptors revealed no difference between the gestational choline levels. These data suggest that attention to maternal choline levels for human pregnancy may be important to the normal functioning of the offspring.

Figure 1

Mean (± SEM) animal weights at the time of recording for sensory inhibition. Rats were 13-14 months old at the time of recording. Choline deficient rats (DEF) were the heaviest followed by normal choline rats (CON) and the choline supplemented (SUP) were the lightest (**p<0.01; CON n=14; DEF n=13, SUP n=7).

Figure 2

TC Ratios for rats gestated on control choline levels (CON, 1.1 g/kg of diet), deficient (DEF; 0 choline) or supplemented groups (SUP; 5 g/kg diet). Both the control and supplemented had TC ratios in the generally normal range for Sprague-Dawley rats. However, the rats gestated on the deficient diet showed significantly higher TC ratio’s indicating loss of sensory inhibition. Data are mean ± SEM, CON n=14; DEF n=13, SUP n=7; **p<.0.01.

Figure 3

Representative wave forms for a rat gestated on control (A) and a rat gestated on deficient (B) choline diets. The choline supplemented rats did not differ from the control rats. The arrows note stimulus onset, the tick marks note the wave of interest.

Figure 4

Sensory inhibition parameters for rats gestated on control (CON), deficient (DEF) and supplemented (SUP) choline diets. Conditioning amplitude (A) showed no effect of maternal dietary choline levels, while test amplitude (C) showed a significant increase in amplitude for animals gestated on the choline deficient diet. The conditioning latency did attain statistical significance in the ANOVA, though no 2 specific groups differed significantly (B). Test latency (D) did not differ between the groups. Data are mean ± SEM; CON n=14; DEF n=13, SUP n=7; **p<0.01.

Figure 5

α-bungarotoxin binding levels in 3 regions of the hippocampus for rats gestated on control (CON), deficient (DEF) and supplemented (SUP) choline diets. None of the regions of the hippocampus (A) Dentate gyrus, (B) CA3 or (C) CA1, showed significant changes in levels of α-bungarotoxin binding as a result of the differences in choline levels in the maternal diet during gestation. Data are mean ± SEM, CON n=14; DEF n=13, SUP n=7.