To investigate the morphology and projections of these excited neurons, we combined sharp electrode recordings with intracellular labeling of individual neurons. Our observations revealed that OT-excited neurons were localized in the CeL, whereas AVP-excited cells were found in the CeM. Subsequent tracing studies showed that the axon collaterals

of the OT-excited cells projected far into the CeM, and immunohistochemical staining showed that they were GABAergic. Further whole-cell patch-clamp recordings indeed showed that the inhibitory effects of OT were related with a massive increase of inhibitory GABAergic currents, induced by the activation of the CeL neurons (Huber et al., 2005). The above set of results led us to the development of a model in which the opposing behavioral effects of AVP and OT are PD-1/PD-L1 targets caused by a Autophagy Compound Library selective activation of two distinct populations: GABAergic neurons in the CeL are activated by OT and project to the CeM, where they exert inhibitory effects on neurons that are directly activated by AVP receptors (Figure 4B). OTergic modulation of the inhibitory projection from the CeL onto the CeM can therefore control the input to the CeL and the subsequent output from the CeM (Huber et al., 2005). Of potential interest in this context, it deserves mentioning that both the ventral CA1 and subiculum send direct projections to

the CeA, especially its capsular part (Cenquizca and Swanson, 2007), which may have the potential to mediate the ventral hippocampal contribution to fear learning (see below). With the aforementioned

homology between the CeA and the BSTl and their high levels of adjacent, nonoverlapping OTR and V1aR binding sites (Veinante and Freund-Mercier, 1997; Figure 4A), the question arises whether opposite effects of OT/AVP can also be found in the BSTl? Though no effects of V1aR activation seem to have been reported yet, strong excitatory effects of OT have been reported (Wilson et al., 2005). Similar to the desensitization differences between the CeA and MeA (Terenzi and Ingram, 2005; ALOX15 see above), OT effects in the BSTl showed faster desensitization compared to the BSTma. Both the CeA and BSTl are reciprocally connected to brainstem centers, particularly the dorsal vagal complex and parabrachial nucleus (Gray and Magnuson, 1987; Moga et al., 1989), and it is possible that OT action in these nuclei is involved in modulating autonomic functions. The nucleus of the solitary tract (NTS) is the major visceral sensory relay nucleus in the brainstem and receives signals from arterial baroreceptors, chemoreceptors, cardiopulmonary receptors, and other visceral receptors in an “organ-topic” manner through inputs from the solitary tract (ST). It is heavily innervated by the CeA and projects back to among others the CeL, as well as to the dorsal motor nucleus of the vagus (DMN) and the rostral ventrolateral medulla (RVLM, Figures 4D and 4E).