Stressed Out Mamas, Their Messed Up Kids And How an Enriched Environment Can Fix All That

prenatal [(pree-nayt-l)] The period between conception and birth.

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)

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

Control Offspring Prenatally Stressed Offspring WITH Environmental Enrichment Prenatally Stressed Offspring WITH Environmental Enrichment Pregnant Mother Prenatal Stress?NoYes Weaning Placed in cage with Enrichment? No Yes

Prenatal day Pregnant mothers stressed for 7 days. Birth Day 0 Postnatal day 22 Prenatally stressed Pups separated into normal or enriched environments Postnatal WEEK 8 Rats killed, hippocampal slices prepared for electrophysiology Control Offspring Prenatally Stressed Offspring WITH Environmental Enrichment Prenatally Stressed Offspring WITH Environmental Enrichment Exp 1. Prenatal Stress and EE

Prenatal day Pregnant mothers stressed for 7 days. Birth Day 0 Postnatal day 22 Prenatally stressed Pups separated into normal or enriched environments Postnatal WEEK 8 Rats killed, slices prepared for electrophysiology Exp 2. Prenatal Stress, EE AND acute stressor on offspring 10 foot shocks over 10 minutes before killing

Experiments 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

Recordings were taken from slices in the CA 1 region of the hippocampus.

Exp. 1

Exp. 2

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 NR 1 + NR 2A Just because of lack of neurogenesis? NR 2B antagonists can reverse the enhanced LTD effect of prenatal stress NR 2B 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?