Developmental periods of choline sensitivity provide an ontogenetic mechanism for regulating memory capacity and age-related dementia

Abstract

In order to determine brain and behavioral sensitivity of nutrients that may serve as inductive signals during early development, we altered choline availability to rats during 7 time frames spanning embryonic day (ED) 6 through postnatal day (PD) 75 and examined spatial memory ability in the perinatally-treated adults. Two sensitive periods were identified, ED 12–17 and PD 16–30, during which choline supplementation facilitated spatial memory and produced increases in dendritic spine density in CA1 and dentate gyrus (DG) regions of the hippocampus while also changing the dendritic fields of DG granule cells. Moreover, choline supplementation during ED 12–17 only, prevented the memory decline normally observed in aged rats. These behavioral changes were strongly correlated with the acetylcholine (ACh) content of hippocampal slices following stimulated release. Our data demonstrate that the availability of choline during critical periods of brain development influences cognitive performance in adulthood and old age, and emphasize the importance of perinatal nutrition for successful cognitive aging.

Prenatal choline availability alters the context sensitivity of Pavlovian conditioning in adult rats

“…Dietary intake of choline by the pregnant mother and later by the infant directly affects brain development. In rodents, perinatal supplementation of choline enhances spatial and temporal cognition, changes that endure across the lifespan Meck and Williams 2003;Meck et al 2008). Conversely, choline deficiency during these sensitive periods results in altered memory function and associated cognitive deficits that also persist (Meck and Williams 1997c.…”

“…It is important to note, however, that although prenatal choline availability has been shown to primarily affect the septum and hippocampus (e.g., Meck and Williams 2003;Mellott et al 2007b;Meck et al 2008), other brain regions such as the frontal cortex and striatum are also modified by these treatments and may contribute to some of the observed behavioral effects (e.g., Meck et al 1989;Sandstrom et al 2002;Mellott et al 2007a;Nag et al 2008). …”

“…When switched to a different context following extinction, however, both choline-supplemented and control rats showed substantial contextual control of responding, whereas choline-deficient rats did not. These data support the view that configural associations that rely on hippocampal function are selectively sensitive to prenatal manipulations of dietary choline during prenatal development.There is increasing evidence that variations in maternal dietary choline intake during the second half of pregnancy cause structural, biochemical, and physiological changes in basal forebrain neurons and their projections to the hippocampal complex as well as long-term cognitive changes in the offspring (e.g., Meck and Williams 2003;McCann et al 2006;Meck et al 2008). We know, for instance, that the adult offspring of pregnant rats supplemented with 4.5 times the amount of choline in the standard laboratory diet display improved memory capacity and precision on the radial-arm maze (e.g., Meck et al…”

“…There is increasing evidence that variations in maternal dietary choline intake during the second half of pregnancy cause structural, biochemical, and physiological changes in basal forebrain neurons and their projections to the hippocampal complex as well as long-term cognitive changes in the offspring (e.g., Meck and Williams 2003;McCann et al 2006;Meck et al 2008). We know, for instance, that the adult offspring of pregnant rats supplemented with 4.5 times the amount of choline in the standard laboratory diet display improved memory capacity and precision on the radial-arm maze (e.g., Meck et al…”

“…There is increasing evidence that variations in maternal dietary choline intake during the second half of pregnancy cause structural, biochemical, and physiological changes in basal forebrain neurons and their projections to the hippocampal complex as well as long-term cognitive changes in the offspring (e.g., Meck and Williams 2003;McCann et al 2006;Meck et al 2008). We know, for instance, that the adult offspring of pregnant rats supplemented with 4.5 times the amount of choline in the standard laboratory diet display improved memory capacity and precision on the radial-arm maze (e.g., Meck et al 1988Meck et al , 1989Williams 1997b, 1999;Tees 1999a), Morris water maze (e.g., Tees 1999b; Tees and Mohammadi 1999;Yang et al 2000;Brandner 2002), as well as facilitation of sustained attention and interval timing (e.g., Meck and Williams 1997a,c;Mohler et al 2001;Cheng et al 2006Cheng et al , 2008aCheng and Meck 2007) compared with offspring of dams fed a standard diet.…”