It is conceivable that local diffusion within

CeL of synaptically released OT to extrasynaptic sites contributes to the described time course. However, if passive diffusion from the hypothalamus were the main route by which OT reaches the CeA, a much longer delay in onset of the effects would be expected (Ludwig and Leng, 2006). So how can we interpret these intermediate selleck chemicals temporal dynamics of OT effects within CeA and on resulting fear responses? Whereas the very rapid onset (within a few seconds or less) of fear responses to aversive threats is vital for survival, temporal precision and speed of fear reduction may not be as important. In fact, a more sluggish return to lower fear states may be adaptive in ambiguous situations with fluctuating threat levels. The present study suggests that the fear-attenuating effects of OT in the CeA are predominantly achieved by synaptic signaling characteristic of a neuromodulatory

effect. However, compared with temporal precision, the gained spatial specificity due to synaptic OT may be the more important determinant of the local axonal release mechanism underlying reduction of fear behavior. Future lack-of-function experiments using light-activated inhibitory proteins would help to understand the significance of axonal OT release during naturally occurring behavioral readjustment after fear. Those experiments would also avoid the potential back-firing Selleck KPT-330 of hypothalamic OT cells by stimulation of their axons, thus

overriding the physiologic situation, in which axonal and dendritic release can be regulated independently. Knobloch et al. (2012) present evidence strongly suggesting an excitatory postsynaptic OT effect on CeL neurons that inhibit CeM output, thus directly reducing expression of fear. It is not known whether OT could also, via presynaptic Terminal deoxynucleotidyl transferase mechanisms, modulate inputs into the CeL during recall of conditioned fear, thereby contributing to the reduction of fear. Given that there are marked sex-specific differences in OT as well OT receptor expression, and anxiolytic effects of oxytocin have been mainly reported in lactating females, it remains to be investigated whether the present findings exclusively obtained in female rats also apply to males and therefore reveal a more general, cross-gender mechanism for attenuation of fear. The new insights provided by the present study into OT function within CeA circuits were gained through combining efficient viral delivery tools, classical electrophysiology, and a robust behavioral paradigm with optogenetic technology.