1• Read Chapters 10 & 11 (10thedition; Ch 2 & 3 for 9thedition)• Reading for Next week’s Discussion Section will be up on Canvas before the weekend.• ***Attendance and Discussion Section• Independent Projects Start Brainstorming!AnnouncementsQuestions• How can single genes affect behavior?– Examples with fruitflies– Examples with mammals– Examples with nonapeptides• Do single genes influence multiple behaviors?– Oxytocin?• Do within and between species mechanisms differ?– Examples with mammals2The nonapeptide lectureDonaldson & Young 20083• Olfactory signatures are processed through the olfactory bulb (OB) . The OB has connections to the reward circuitry in the Brain that also receive Oxytocin inputs.• IMPORTANT connection between SENSORY input & REWARD!!Reward & Olfaction & Oxytocin4• Does the Oxytocin Receptor (OTR) distribution in the Reward region of the brain (Nacc) play a role in mediating maternal bonds/care in prairie voles?• great variation in maternal care in prairie voles. – 55% of naïve (virgin) adult female prairie voles show “spontanteus” maternal behavior when first exposed to pups (Olazabal & Young 2005)– 45% of these adult virgin females ignore pups– Is the differences related to OTR distribution in the NA?Reward & Maternal Bonding?5OTR & Maternal care• OTR binding was greater in shell region of Nucleus Accumbens (NAsh) in maternal than non-maternal virgin femalesOlazabal & Young 2006 NeuroscienceNA sh• OTR density in NAsh and maternal behavior is correlated in virgin prairie vole females (r = 0.47)Olazabal & Young 2006 Hormones & Behavior6Interspecific variation in OTR in the NA• Prairie voles had significantly more OTR density in NA than other species• Are female parental bonding pathways (OT) related to Pair-bonding pathways?Olazabal & Young 2006 Hormones & BehaviorIncreasing Maternal Care/Bonding Increasing Pair Bonding/Monogamy 7Effects of intracerebroventricular oxytocin (OT) on female partner-preferences in prairie voles.OTA= Oxytocin Receptor Antagonist8prairie voleMales(AVP in Ventral Pallidum)Females(OT inNucleus Accumbens)Young & Wang 2004Blocking peptide in Reward regions—Blocks Partner Bonding behaviorOTA = Oxytocin Antagonist= associated with Reward Pathway9Does INCREASING receptor density lead to INCREASING pair bonding?Prairie vole(lots of individual variation)Oxytocin Receptor density in typical femalesMeadow vole(low variaiton)OTR over-expression (via viral vector) in femalesRoss et al 200910Does INCREASING receptor density lead to INCREASING pair bonding?Prairie voleMeadow voleOTR over-expression (via viral vector) in femalesRoss et al 2009Compared pair-bonding behavior of manipulated females relative to controls (sham or GFP)11• Olfactory signatures are processed through the olfactory bulb (OB) . The OB has connections to the reward circuitry in the Brain that also receive Oxytocin inputs.• IMPORTANT connection between SENSORY input & REWARD!!Reward & Olfaction & Oxytocin12If Reward Pathways are implicated in pair bonding, what other molecules in the brain should be involved?DA = DopamineFemale prairie voles13If Reward Pathways are implicated in pair bonding, what other molecules in the brain should be involved?When they looked inside the NA, they found HIGH densities of D2 receptors (a dopamine receptor)D2 receptors > D1 receptors14If Reward Pathways are implicated in pair bonding, what other molecules in the brain should be involved?What would you do next to test the role of D2 in female pair bonding?15• The Nucleus Accumbens (NAcc) coordinates the inputs of OT and DA (reward neurotransmitter) to elicit response.• Manipulations of OTR AND D2 in female prairie vole NAcc resulted in manipulating Pair-bonding (blocking it & augmenting it). • Not the case for meadow volesReward & Female BondingPVN= Paraventricular Nucleus of the Hypothalamus16Effects of intracerebroventricular oxytocin (OT) and arginine vasopressin (AVP) on partner-preferences in prairie voles.V1a= Vasopressin Receptor Antagonist17prairie volemontane voleyoung et al, nature 1999Males from 2 species respond differently to AVPCSF= control fluid injection (Cerebrospinal Fluid) 18prairie volemontane voleLim et al, Nature 2004Differences in AVP response due to differences in V1a receptor expressionVentral Pallidum has higher V1a expression19prairie voleMales(AVP in Ventral Pallidum)Females(OT inNucleus Accumbens)Young & Wang 2004Blocking peptide in key brain region—Blocks Partner Bonding behaviorV1aRa = Vasopressin Receptor 1a ANTAGONIST20Test it with Transgenics• The association between brain V1a receptor binding patterns and monogamy in male voles suggests a functional relationship: prairie voles are monogamous because of their regional sensitivity to endogenous AVP. • Researchers put the prairie vole AVP receptor into a promiscuous species (house mouse) (Young et al., 1999) & then injected them with AVP (arginine vasopressin)• Then they became more specific and put the prairie vole AVP receptor gene DIRECTLY into the ventral Pallidium of the promiscuous montane vole and added AVP (Lim et al 2004)21Results mice (normally non-monogamous) Increased Affilliative Behavior (monogamous-like behaviors)Behavior Towards Ovariectomized FemalesBehavior Towards Cotton BallsCSF= control fluid injection (Cerebrospinal Fluid) 22Making Meadow Voles Monogamous(Lim et al., 2004)Used a viral vector to transfer the vasopressin receptor gene into the ventral forebrain of The meadow vole**Both meadow & montane voles are promiscuouspartnerstranger23Making Meadow Voles Monogamous(Lim et al., 2004)**Both meadow & montane voles are promiscuouspartnerstranger24• Olfactory signatures of sexual partner are processed through the amygdala (Olfactory Bulb (OB) -> Medial Amygdala (MeA).• This leads to the activation of neuropeptide(AVP) and Dopamine receptors in the reward circuitry (at Ventral Pallidum (VP)) linking the partner’s olfactory signature to copulatory reward.• AVP from the amygdala (MeA) and Dopamine (DA) from the Nucleus Accumbens (Nacc) project on the VP where the receptors mediate the responseMcGraw & Young 2010Reward Circuitry & Male Pair BondingPVN= Paraventricular Nucleus of the Hypothalamus25If Reward Pathways are implicated in pair bonding, what other molecules in the brain should be involved?26If Reward Pathways are implicated in pair bonding, what other molecules in the brain should be