Neuromodulation by Oxytocin and Vasopressin Ron Stoop  Neuron  Volume 76, Issue 1, Pages 142-159 (October 2012) DOI: 10.1016/j.neuron.2012.09.025 Copyright © 2012 Elsevier Inc. Terms and Conditions

Figure 1 Peptide Sequences of Homologous Vasopressin and Oxytocin Prohormones Top: outline of basic structure for the OT and VP prohormones. Lower: aligned individual sequences of VP and OT in different species. Neuron 2012 76, 142-159DOI: (10.1016/j.neuron.2012.09.025) Copyright © 2012 Elsevier Inc. Terms and Conditions

Figure 2 Intracellular Pathways for Oxytocin and Vasopressin Different intracellular pathways activated by OT or VP according the specific G proteins that they activate, leading to activation of TTX-insensitive Na+ channels or inhibition of K+ channels. Note the selective recruitment of beta arrestin by Gq11 activation of OT, leading to internalization of the OTR, but not by Atosiban, which only activates the Gi/o-coupled OTR. Neuron 2012 76, 142-159DOI: (10.1016/j.neuron.2012.09.025) Copyright © 2012 Elsevier Inc. Terms and Conditions

Figure 3 Neuromodulation by OT and AVP of Systems Involved in Social Signaling OTR-expressing (in red) and AVPR-expressing (in green) regions in the brain and their connections involved in transmitting olfactory stimuli and pheromones to brain regions important for signaling social relevance. Shaded panels indicate levels at which insets were taken that are shown below. (A) Olfactory bulb showing MCs with cell body excited by AVP and dendrites that excite (arrows) and also in return are inhibited by GC dendrites (squares) that are themselves inhibited by OT. (B) BSTma-expressing OTRs on cell bodies excited by OT. (C) Posterodorsal part of medial amygdala (MePD)-expressing OTRs on cell bodies excited by OT (MePV = posteroventral part of medial amygdala). (D) VMH-expressing OTRs on dendrites that are excited by OT. Neuron 2012 76, 142-159DOI: (10.1016/j.neuron.2012.09.025) Copyright © 2012 Elsevier Inc. Terms and Conditions

Figure 4 Neuromodulation by OT and AVP in Regions for Alert and Homeostasis OTR-expressing (in red) and AVPR-expressing (in green) regions in the brain and their connections involved in fear and anxiety. Shaded panels indicate levels at which insets were taken that are shown below. (A) BST with laterodorsal (BSTld) part expressing OTRs on cell bodies excited by OT and posterolateral (BSTlp) part expressing AVPRs. An inhibitory connection between both areas has been suggested similar to the homologous CeA. (B) CeA with lateral/capsular part expressing OTRs directly excited by OT and medial part expressing AVPRs directly excited by AVP and indirectly inhibited by OT-activated inhibitory projections from CeL. (C) Dorsal part of lateral parabrachial nucleus (LPBD) expressing AVPRs with neurons receiving excitatory input from neurons lateral to the superior cerebellar peduncle (scp) that is presynaptically inhibited by AVP (MPB = medial parabrachial nucleus). (D) DMN neurons directly excited by OT and indirectly inhibited through presynaptic inhibitory effects of AVP on synapses in the NTS. (E) RVLM neurons directly excited by AVP and NA neurons indirectly inhibited by inhibitory neurons excited by AVP. Neuron 2012 76, 142-159DOI: (10.1016/j.neuron.2012.09.025) Copyright © 2012 Elsevier Inc. Terms and Conditions

Figure 5 Neuromodulation by OT and AVP of Systems Involved in Memory and Learning, as well as of Sensory and Motor Systems OTR-expressing (in red) and AVPR-expressing (in green) regions in the brain and their connections involved in memory and learning (left side) and sensory and motor systems (right side). Shaded panels indicate levels at which insets were taken that are shown below. (A) Lateral septal region (LS) with dorsal part (LSD) expressing OTRs on cell bodies excited by OT and ventral part (LSV) expressing AVPRs on inhibitory neurons inhibiting projections neurons. (B) Hippocampal region (Hipp) with dentate gyrus (DG)- and CA3-expressing AVPRs and CA1- and subiculum-expressing OTRs on inhibitory interneurons in the pyramidal layer that inhibit pyramidal neurons. (C) Facial nucleus (VII)-expressing AVPRs on neurons excited by AVP. (D) Hypoglossal nucleus (XII)-expressing AVPRs on neurons that are directly excited by AVP, indirectly excited by AVP activation of excitatory glutamatergic premotor neurons, and indirectly inhibited by OT activation of inhibitory interneurons releasing GABA or glycine (Wrobel et al., 2010). (E) Spinal cord expressing OTRs on dorsal side that presynaptically excite local inhibitory neurons and on ventral side AVP-excited neurons which are inhibited by projections from OT-excited neurons, suggested to originate from the dorsal part. Neuron 2012 76, 142-159DOI: (10.1016/j.neuron.2012.09.025) Copyright © 2012 Elsevier Inc. Terms and Conditions