Electron microscopy confirmed the presence of synaptic contacts between OT immunoreactive axon terminals and dendrites in the CeL. Furthermore, colocalization of the glutamate transporter VGLUT2 indicated that these synapses are likely to release

glutamate in addition to OT. The presence of OT axonal projections in the CeA leads to the question of how their stimulation affects information processing in the CeA. The authors, as well as others, have shown that CeM output cells are under tight inhibitory control by GABAergic interneurons located in CeL and that exogenous application learn more of OT in the CeL results in inhibition of neuronal activity in the CeM (Cassell et al., 1999, Huber et al., 2005, Ehrlich et al., 2009 and Viviani Apoptosis Compound Library nmr et al., 2011). The CeM, in turn, is well known as the major output by which the amygdala determines the expression of fear-related behaviors (LeDoux, 2000 and Maren and Quirk, 2004). A microcircuit within CeA important for acquisition as well as expression of fear has recently been characterized (Haubensak et al., 2010). Pharmacological inactivation of CeL in mice resulted in freezing, a characteristic fear behavior, and this effect could also be triggered by optogenetic activation of CeM (Ciocchi et al., 2010). Does local, endogenous release of OT affect neuronal activity within this microcircuit? In the present study, this question was initially

addressed using an in vitro optogenetic approach in acute brain slices. Fiber terminals of channelrhodopsin-2 (ChR2)-expressing OT neurons in the CeL were exposed to blue light during whole-cell recordings of CeL neurons. Interestingly, one-third of the recorded

cells responded to light exposure with an increase in action potential frequency, an effect many that was blocked by application of an OT antagonist to the slice. The authors then investigated the downstream consequences of this increased activity of CeL neurons by recording from their targets in the CeM. Light stimulation of OT fibers in the CeL resulted in a dramatic increase in the frequency of inhibitory postsynaptic currents in CeM neurons. Again, this effect could be prevented by blocking OT receptors. Knobloch et al. (2012) next investigated whether local axonal release of OT within CeL would have an effect on fear-related behavior in vivo. To accomplish this, optical fibers targeting the CeL were implanted in rats expressing ChR2 in hypothalamic OT neurons (Figure 1). The authors hypothesized that evoked OT release within CeL should lead to attenuation of fear. To test this, rats were first run through a contextual fear conditioning procedure during which they received several mild electrical shocks in a novel environment. When these rats were put back into the context in which they had been shocked, they exhibited strong freezing responses indicative of high fear levels.