• Read Chapters 10 & 11• Read pp 407- 420 for next week• Discussion Reading will be up by end of FridayAnnouncements1Questions• How can behavioral plasticity be regulated?– Maternal Care– Reproductive Strategies– Anti-predatory Responses2Red–Glucocorticoid ReceptorsDifferential expression of Stress Regulating Receptors (GR)Red–Corticotropin-Releasing HormoneDifferential Response to Stress:Hormonal & Behavioral3How does behavior modify gene expression?• ‘differential’ methylation of promotor region of the Glucocorticoid receptor gene• Methylation: adding of a methyl group (CH3), prevents gene transcription• Maternal care altered methylation environment & subsequent gene expressionWeaver et al. 2004Low Levels of Care(**HIGH methylation)High Levels of Care(Low Methylation)4Cellular and Molecular pathways linking handling to reduced stress reactivity• 5-HT (serotonin)• Nr3c1 is the gene that leads to GR in the hippocampus(Champagne 2013)• Licking - > • Increased Serotonin (-> increased GR transcription) • Also leased to DE-methylation of the transcription site for GR5The Theory behind how this is happening?• Maternal LG leads to Demethylation via Increased histone acetylation (a process that promotes transcription factor binding by changing the charge of the histones—so they don’t bind to the DNA so tightly)• So when they pharmacologically increased histone acetylation (adding TSA)…found:(Weaver et al 2005)6• Decreased Methylation in the Poor Maternal care group (TSA + lowLG)The Theory behind how this is happening?• Maternal LG leads to Demethylation via Increased histone acetylation (a process that promotes transcription factor binding by changing the charge of the histones—so they don’t bind to the DNA so tightly)• So when they pharmacologically increased histone acetylation (adding TSA)…found:(Weaver et al 2005)7• And MORE GR in the Dorsal Hippocampus (TSA + lowLG)How about the Other Direction?• Yes• Given the difference in methylation patterns between High & Low LG-ABN mothers, researchers were curious could they change the Stress Response of mom’s if they changed the Methylation Environment?• Prediction:• If increase the methylation substrate in the brain (hippocampus) what would happen to the Stress Response of the Mom’s?• And the Maternal Behavior of these mom’s?8Rat Brains on Meth(ionine)• Infused the hippocampus with methionine• Compared Stress Response across groups• Compared GR expression Patterns(Weaver et al 2005)Treatments9Can Environmental Enrichment Reverse the effects of Maternal Separation?• Darlene Francis & Michael Meaney ran the following experiment:• Exposed rats to either Handling (H) or Maternal Separation (MS) for first 2 weeks of life• Then exposed sets of H and MS rats to either a standard social housing (control) or Environmental Enriched (EE) housing until day 70• Then, as adults—tested for stress responseFrancis et al 2002 J Neurosci10Can Environmental Enrichment Reverse the effects of Maternal Separation?• Enriched Environment (EE) was able to reverse the effects of Maternal Separation (MS) in terms of circulating stress hormones (corticosterone)Francis et al 2002 J NeurosciH/Ctl = Handled as juv + control living conditionsH/EE = Handled as juv + Enriched environmentMS/ctl= Maternally Separated for 1st2 weeks + control conditionsMS/EE = Maternally Separated for 1st2 weeks + enriched environment11Can Environmental Enrichment Reverse the effects of Maternal Separation?• And behavior? • Enriched Environment recovered “healthy” stress response following Maternal SeparationFrancis et al 2002 J Neurosci12What about the Glucocorticoid Receptors in the BRAIN?• Enriched Environment did NOT alter the expression of GR or CRF in key brain regions involved in stress response (Hippocampus regions)Francis et al 2002 J NeurosciDentate gyrus HippocampusCRF(hypothalamus)GR mRNA13Can Environmental Enrichment Reverse the effects of Maternal Separation?• Behavior is reversible via changes in environment• Mechanisms differ• Early Maternal effects influence gene expression in key region controlling the negative feedback loop of the HPA axis (stress response)• Later environmental changes modify the stress response at lower levels in the HPA hierarchy (compensatory effects)• Compensatory effects might effectively offset the effects of early environmental stress on the phenotype• What is the compensatory mechanisms?• Currently unknown (but Serotonin implicated)Francis et al 2002 J Neurosci14What other genes do you expect to play a role in Maternal Care in this system?• Is all of this maternal care variation driven solely by variation in Glucocorticoid Receptors?• No• Oxytocin Receptors & Estrogen Receptors are also affected by early rearing environment• ERα shows differential expression in the MPOAChampagne et al 200615And there is Differential methylation of the ER1b promotor• ERα shows differential expression in the MPOA• Avg cystosine methylation differs between female offspring of High and Low LG mothers.• Higher methylation in daughters of LOW LG momsChampagne et al 200616What other genes do you expect to play a role in Maternal Care in this system?• Oxytocin Receptors also affected by early rearing environment & stressChampagne & Meaney 200617Does variation in ER and OTR influence other Female Behaviors?• Yes• & this leads to a Trade-Off in Female Reproductive StrategiesChampagne 201118The Neural Basis of Parental Care?• Variation in care received as an offspring determines the adult phenotype• Epigenetics: mechanism to shape the phenotype to environment (environmental programming)• Maternal effects may be able to transmit information about the environment that can lead to ‘adaptive’ modifications of behavior19The Neural Basis of Parental Care?• Epigenetics allows for ‘plasticity’, having the phenotype shaped by the environment• Expect more behaviors to have epigenetic effects?20Epigenetics and Anti-predatory behavior?• Field crickets (Gryllus pennsylvanucus) are subject to predation by the wolf spider (Hogna helluo)• If you expose Gravid Female Crickets to the Hogna Spiders…do you see a change in the anti-predatory responses of their offspring?21Anti-predatory behavioral response towards predatory chemical cues• Offspring of Hogna-Exposed mothers showed greater anti-predatory response towards Hogna