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 paperLateral Palium in

fishesHippocampus in

mammals

Physiology of Prenatal StressAlters 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 Stressor10 foot shocks

over 30 minutesDaily for 1 week~ 2 weeks before

birth

Enriched Environment (EE)

Enriched EnvironmentEE can reverse cognitive deficits from early life

stressEmotional reactivity, motor skills and spatial

learning Early postnatal EE can counteract deficits in

hippocampal neurogenesis brought on by prenatal stress

Enriched Cage vs. Normal CageEnriched Environment Normal Environment

60 x 50 x 70 cm = 210K cu cm

2 FloorsWood ShavingsRunning wheel, shelter,

toys, chain, swing, tunnels

60 x 40 x 25 cm = 60K cu cm

Bedding?

Questions to be answeredHow does prenatal stress affect synaptic

plasticity in the hippocampusHow 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 Offsprin

g

Prenatally Stressed Offspring

Prenatally Stressed Offspring

WITH Environmental

Enrichment

Pregnant Mother

Prenatal Stress?

No Yes

Weaning

Placed in cage with

Enrichment?

No Yes

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

Postnatal WEEK 8

Rats killed, hippocampal

slices prepared for

electrophysiology

Control Offsprin

g

Prenatally

Stressed Offsprin

g

Prenatally Stressed Offspring

WITH Environmental

Enrichment

Exp 1. Prenatal Stress and EE

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

Postnatal WEEK 8

Rats killed, slices prepared

for electrophysiolo

gy

Exp 2. Prenatal Stress, EE AND acute stressor on offspring

10 foot shocks over 10 minutes before killing

Experiments 1 + 2 electrophysiologyLTP LTDStrengthening of a given

synapseCorrelation to learning

something completely newThe bench is hot

Inhibition of a given synapse

Correlation to learning to disregard something previously learnedThe bench isn’t hot at

night

Recordings were taken from slices in the CA1 region of the hippocampus.

Exp. 1

Exp. 2

Morris Water Maze(Classic Spatial Learning Task)

Morris Water Maze(Classic Spatial Learning Task)6 swimming trials per day/ 4 daysDay 5 platform removed

Measured when rat crossed where platform SHOULD be

ResultsIn 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.

DiscussionPrenatal stress impairs behavior due to

sensitive period of brain circuitry formationLTP depressedLTD enhancedSpatial learning inhibitedAcute stress effects of LTP + LTD exacerbated?

Decrease in hippocampal neurogenesis from prenatal stress

DiscussionMechanisms behind the LTP + LTD?

Prolonged glucocorticoid increaseNorepinephrine increases in hippocampusAcetylcholine increases in hippocampus

Decrease in synaptic gene expressionMost notably NR1 + NR2A

Just because of lack of neurogenesis?NR2B antagonists can reverse the enhanced LTD

effect of prenatal stressNR2B subunit of NMDA receptor thought to play roll

in LTD

DiscussionEnriched Environment is REALLY cool

Reverses most problems associated with prenatal stress in animal models

Use it or loose it?