PT - JOURNAL ARTICLE AU - Cynthia D. Fast AU - John P. McGann TI - Amygdalar Gating of Early Sensory Processing through Interactions with Locus Coeruleus AID - 10.1523/JNEUROSCI.2797-16.2017 DP - 2017 Mar 15 TA - The Journal of Neuroscience PG - 3085--3101 VI - 37 IP - 11 4099 - http://www.jneurosci.org/content/37/11/3085.short 4100 - http://www.jneurosci.org/content/37/11/3085.full SO - J. Neurosci.2017 Mar 15; 37 AB - Fear- and stress-induced activity in the amygdala has been hypothesized to influence sensory brain regions through the influence of the amygdala on neuromodulatory centers. To directly examine this relationship, we used optical imaging to observe odor-evoked activity in populations of olfactory bulb inhibitory interneurons and of synaptic terminals of olfactory sensory neurons (the primary sensory neurons of the olfactory system, which provide the initial olfactory input to the brain) during pharmacological inactivation of amygdala and locus coeruleus (LC) in mice. Although the amygdala does not directly project to the olfactory bulb, joint pharmacological inactivation of the central, basolateral, and lateral nuclei of the amygdala nonetheless strongly suppressed odor-evoked activity in GABAergic inhibitory interneuron populations in the OB. This suppression was prevented by inactivation of LC or pretreatment of the olfactory bulb with a broad-spectrum noradrenergic receptor antagonist. Visualization of synaptic output from olfactory sensory neuron terminals into the olfactory bulb of the brain revealed that amygdalar inactivation preferentially strengthened the odor-evoked synaptic output of weakly activated populations of sensory afferents from the nose, thus demonstrating a change in sensory gating potentially mediated by local inhibition of olfactory sensory neuron terminals. We conclude that amygdalar activity influences olfactory processing as early as the primary sensory input to the brain by modulating norepinephrine release from the locus coeruleus into the olfactory bulb. These findings show that the amygdala and LC state actively determines which sensory signals are selected for processing in sensory brain regions. Similar local circuitry operates in the olfactory, visual, and auditory systems, suggesting a potentially shared mechanism across modalities.SIGNIFICANCE STATEMENT The affective state is increasingly understood to influence early neural processing of sensory stimuli, not just the behavioral response to those stimuli. The present study elucidates one circuit by which the amygdala, a critical structure for emotional learning, valence coding, and stress, can shape sensory input to the brain and early sensory processing through its connections to the locus coeruleus. One function of this interaction appears to be sensory gating, because inactivating the central, basolateral, and lateral nuclei of the amygdala selectively strengthened the weakest olfactory inputs to the brain. This linkage of amygdalar and LC output to primary sensory signaling may have implications for affective disorders that include sensory dysfunctions like hypervigilance, attentional bias, and impaired sensory gating.