1. VASOPRESSIN-DEPENDENT NEURAL CIRCUITS UNDERLYING BOND FORMATION IN THE MONOGAMOUS PRAIRIE VOLE LIM, MM AND YOUNG, LJ. NEUROSCIENCE, 2004. Yvonne Pao November 7, 2008

2. Neural Control of Social Behaviors  Seems to involve :  Arginine vasopressin (AVP) + V1a receptor (V1aR)  Reward circuitry: Ventral pallidum (VP) Mediodorsal thalamus (MDthal)  Medial amygdala Social memory formation Olfactory/somatosensory processing of sociosexual stimuli  Monogamous prairie voles have high levels of V1aR in these structures

3. Hypothesis  Sociosexual and reward circuits underlie pair bond formation  Approach: 1. Examine Fos induction in these circuits 2. Block V1aR in specific structures 3. Adeno-associated viral (AAV) vector gene transfer to increase V1aR gene density in specific regions

4. Experiment 1: Fos Induction  Subjects:  Sexually naïve male prairie voles  70-100 days of age  3 groups: 1. Isolated 2. Exposed to co-housed siblings 3. Paired with female voles (same age)

5. Experiment 1: Fos Induction

7. Isolated animalMated animal Radiolabeled V1aR

8. Medial Amygdala MDthal

9. Experiment 2: V1aR Blockade  Subjects: sexually naïve adult male prairie voles  Bilateral infusion of V1aR antagonist into:  Lateral ventricle (control)  Ventral pallidum  Medial amygdala  MDthal  Test for partner preference Aragona and Wang 2008

11. Nissl: Bilateral placement of V1aR antagonist in VP Nissl: Bilateral placement of V1aR antagonist in medial amygdala Radiolabeled V1aR antagonist confined to VP Nissl: Bilateral placement of V1aR antagonist in MDthal

12. Experiment 3: Increase V1aR in VP  Subjects: sexually naïve, adult male prairie voles  Unilateral infusion into VP:  AAV-V1a viral vector  AAV-lacZ (control)  Animals recovered for 2 weeks  Two groups (2 h):  Exposed to receptive females  Isolated  Partner preference and Fos expression analyzed

13. Mated male prairie vole Isolated male prairie vole Autoradiography of V1aR Difference in Fos cells

14. Mating-induced Fos Expression  Sociosexual and reward structures activated after mating  Medial amygdala  Bed nucleus of stria terminalis  Medial preoptic area  Regions may be involved in general social behaviors  Fos activation not dependent solely on mating behavior  Many steps involved in mating with female

15. VP and Pair bonding  Vasopressin in medial amygdala and MDthal not heavily involved in pair bonding  VP heavily interconnected with NAcc and mesolimbic dopamine reward pathway  V1aR in VP found in the monogamous:  Pine vole  Marmoset  California mouse

16. VP and Vasopressinergic Transmission  Vasopressinergic neurotransmission in the ventral pallidum is critical for pair bond formation in the prairie vole  Future work: Vasopressinergic neurotransmission in ventral forebrain of prairie voles?