Dolen & Malenka 2013

24
Kristen Delevich Journal Club 10/15/13

description

Journal club for 2013 Nature article, "Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin.

Transcript of Dolen & Malenka 2013

Page 1: Dolen & Malenka 2013

Kristen DelevichJournal Club 10/15/13

Page 2: Dolen & Malenka 2013

Prairie vole Montane vole

Insel and Shapiro 1992

125I-OTA bindingOTR and pair-bonding

Photo: Todd Ahern/Emory University/via the San Francisco Chronicle

Page 3: Dolen & Malenka 2013
Page 4: Dolen & Malenka 2013

How to make love like a prairie vole??

Kimberly A. Young, Kyle L. Gobrogge, Yan Liu, Zuoxin Wang 2011

Page 5: Dolen & Malenka 2013

Love and other drugs

photograph copyright Jean-Louis Klein and Marie-Luce Hubert

Page 6: Dolen & Malenka 2013

2013

2012

Complex role of Oxytocin signaling

Page 7: Dolen & Malenka 2013

Do OTergic hypothalamic inputs to NAc even exist in male mice?

Page 8: Dolen & Malenka 2013

Male mice receive substantial OTergic input from PVN but not SON

Page 9: Dolen & Malenka 2013

Oxytocin is required for social CPP

Page 10: Dolen & Malenka 2013

NAc delivery of OT-A sufficient to block social CPP

Page 11: Dolen & Malenka 2013

Cocaine-induced CPP doesn’t require Oxytocin

Page 12: Dolen & Malenka 2013

Oxytocin induces LTD onto NAcc MSNs

Allen Brain Atlas

Page 13: Dolen & Malenka 2013

Social housing engages OT-LTD, OT-LTD targets D1 & D2 NAc MSNs

Page 14: Dolen & Malenka 2013

Oxytocin-induced LTD is presynaptic

Page 15: Dolen & Malenka 2013

Selective ablation of OTRs in cOTR mice

AAV-Cre

Rabies-Cre

Page 16: Dolen & Malenka 2013

Presynaptic OTRs are required for social CPP

Page 17: Dolen & Malenka 2013

OTR-expressing cells that project to NAc

Page 18: Dolen & Malenka 2013

Ruling out vSub and ACC

Page 19: Dolen & Malenka 2013

Dorsal-raphe presynaptic OTRs necessary for social CPP and OT-LTD

Page 20: Dolen & Malenka 2013

NAc projecting dorsal raphe neurons are serotonergic

Page 21: Dolen & Malenka 2013

OT-LTD acts through 5HTR1B 5H

T1R

B a

goni

st5H

T1R

B a

ntag

. + O

T

5HT

1R

B a

goni

st +

OT

ant

ag.

Page 22: Dolen & Malenka 2013

5HTR1B antagonist in NAc blocks social CPP

Page 23: Dolen & Malenka 2013

Circuit Summary

Downstream target?

Page 24: Dolen & Malenka 2013

Mechanism?

2009