Stressed Out Mamas, Their Messed Up Kids And How an Enriched Environment Can Fix All That
Last weeks paper • Lateral Palium in fishes • Hippocampus in mammals
Physiology of Prenatal Stress • Alters synaptic function (to detriment of offspring) • Gene expression • Decreases synaptic densities in the hippocampus of offspring • Induces marked absence of hippocampal neurogenesis • Reduces density of nitric-oxide producing neurons in dentate and parts of hippocampus in offspring
Prenatal Stressor • 10 foot shocks over 30 minutes • Daily for 1 week • ~ 2 weeks before birth
Enriched Environment • EE can reverse cognitive deficits from early life stress • Emotional reactivity, motor skills and spatial learning • Early postnatal EE can counteract deficits in hippocampal neurogenesis brought on by prenatal stress
Enriched Cage vs. Normal Cage Enriched Environment Normal Environment • 60 x 50 x 70 cm = 210K cu cm • 2 Floors • Wood Shavings • Running wheel, shelter, toys, chain, swing, tunnels • 60 x 40 x 25 cm = 60K cu cm • Bedding?
Questions to be answered • How does prenatal stress affect synaptic plasticity in the hippocampus • How does it work after an acute stressor • How does prenatal stress affect a spatial learning task preformed by rats • Can either of these things be reversed by Enriched Environment
Pregnant Mother No Prenatal Stress? Yes Weaning Control Offspring Placed in cage with Enrichment? No Yes Prenatally Stressed Offspring Prenatally Stressed Offspring WITH Environmental Enrichment
Exp 1. Prenatal Stress and EE Control Offspring Prenatally Stressed Offspring Prenatally Stressed Offspring WITH Environmental Enrichment Postnatal WEEK 8 Rats killed, hippocampal slices prepared for electrophysiology Prenatal day 19-13 Pregnant mothers stressed for 7 days. Birth Day 0 Postnatal day 22 Prenatally stressed Pups separated into normal or enriched environments
Exp 2. Prenatal Stress, EE AND acute stressor on offspring Postnatal WEEK 8 Rats killed, slices prepared for electrophysiology Postnatal day 22 Prenatally stressed Pups separated into normal or enriched environments Prenatal day 19-13 Pregnant mothers stressed for 7 days. Birth Day 0 10 foot shocks over 10 minutes before killing
Experiments 1 + 2 electrophysiology LTP LTD • Strengthening of a given synapse • Correlation to learning something completely new • The bench is hot • Inhibition of a given synapse • Correlation to learning to disregard something previously learned • The bench isn’t hot at night
Morris Water Maze(Classic Spatial Learning Task) • 6 swimming trials per day/ 4 days • Day 5 platform removed • Measured when rat crossed where platform SHOULD be
Results • In a nutshell…. All changes in LTP, LTD and spatial learning brought upon by prenatal stress are reversed with environmental enrichment at an early age.
Effect of prenatal stress on hippocampal neurogenesis + EE reversal Lemaire, V., Lamarque, S., Moal, M. L., Piazza, P. V., & Abrous, D. N. (2006). Postnatal stimulation of the pups counteracts prenatal stressinduced deficits in hippocampal neurogenesis. Biological Psychiatry, 59, 786–792.
Discussion • Prenatal stress impairs behavior due to sensitive period of brain circuitry formation • LTP depressed • LTD enhanced • Spatial learning inhibited • Acute stress effects of LTP + LTD exacerbated? • Decrease in hippocampal neurogenesis from prenatal stress
Discussion • Mechanisms behind the LTP + LTD? • Prolonged glucocorticoid increase • Norepinephrine increases in hippocampus • Acetylcholine increases in hippocampus • Decrease in synaptic gene expression • Most notably NR1 + NR2A • Just because of lack of neurogenesis? • NR2B antagonists can reverse the enhanced LTD effect of prenatal stress • NR2B subunit of NMDA receptor thought to play roll in LTD
Discussion • Enriched Environment is REALLY cool • Reverses most problems associated with prenatal stress in animal models • Use it or loose it?