Laterally connected inhibitory circuitry is found throughout the nervous system, including many early sensory processing systems. The extent to which it plays a role in shaping neuronal stimulus selectivity in systems like olfaction, however, which lack a simple twodimensional representation of their stimulus space, has remained controversial. We examined this issue using an experimental preparation that allowed electrophysiological recording from the accessory olfactory bulb of an anesthetized mouse during the controlled delivery of pheromonal stimuli, in this case derived from the urine of male and female mice. We found that individual neurons were often highly selective for the sex of the urine donor. Examination of both explicitly inhibitory responses, as well as responses to mixtures of male and female urine, revealed that laterally connected inhibition was both prevalent and of large magnitude, particularly for male-selective neurons. Pharmacological manipulation of this inhibition resulted in a shift in many neurons' stimulus selectivities. Finally, we found that a behavioral response (pregnancy block) evoked by the presence of unfamiliar male urine could be suppressed by the addition of female urine to the stimulus, demonstrating that this system displays a behavioral opponency consistent with neural inhibition. Together, these results indicate that laterally connected inhibitory circuitry in the accessory olfactory bulb plays an important role in shaping neural selectivity for natural stimuli.

A central role for noradrenergic dysregulation in the pathophysiology of post-traumatic stress disorder (PTSD) is increasingly suggested by both clinical and basic neuroscience research. Here, we integrate recent findings from clinical and animal research with the earlier literature. We first review the evidence for net upregulation of the noradrenergic system and its responsivity to stress in individuals with PTSD. Next, we trace the evidence that the α noradrenergic receptor antagonist prazosin decreases many of the symptoms of PTSD from initial clinical observations, to case series, to randomized controlled trials. Finally, we review the basic science work that has begun to explain the mechanism for this efficacy, as well as to explore its possible limitations and areas for further advancement. We suggest a view of the noradrenergic system as a central, modifiable link in a network of interconnected stress-response systems, which also includes the amygdala and its modulation by medial prefrontal cortex. Particular attention is paid to the evidence for bidirectional signaling between noradrenaline and corticotropin-releasing factor (CRF) in coordinating these interconnected systems. The multiple different ways in which the sensitivity and reactivity of the noradrenergic system may be altered in PTSD are highlighted, as is the evidence for possible heterogeneity in the pathophysiology of PTSD between different individuals who appear clinically similar. We conclude by noting the importance moving forward of improved measures of noradrenergic functioning in clinical populations, which will allow better recognition of clinical heterogeneity and further assessment of the functional implications of different aspects of noradrenergic dysregulation.

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