Amygdalar Gating of Early Sensory Processing through Interactions with Locus Coeruleus

Abstract

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.

Persistent, generalized hypersensitivity of olfactory bulb interneurons after olfactory fear generalization

“…We used reporter mice (Chen et al, 2013; Taniguchi et al, 2011; Zariwala et al, 2012) to visualize CS-evoked GCaMP signals in populations of PG interneurons (Fast & McGann, 2017; Wachowiak et al, 2013) 1 day before, 1 day after, and 1 month after fear conditioning (Figure 1A). Because of the orderly mapping of odor receptors in the nose onto the olfactory bulb glomeruli, odors evoke focal increases in fluorescence in PG cells innervating odor-specific subsets of glomeruli (Figure 1G–I).…”

“…Mice used for optical neurophysiology expressed the genetically-encoded calcium indicators GCaMP3 (Zariwala, Borghuis, Hoogland, Madisen, Tian, De Zeeuw et al, 2012) (Jackson Laboratory, stock #014538) or GCaMP6f (Chen, Wardill, Sun, Pulver, Renninger, Baohan et al, 2013) (Jackson Laboratory, stock #024105) via cre recombinase-mediated recombination in cells expressing the gad2 gene (Taniguchi, He, Wu, Kim, Paik, Sugino et al, 2011) (Jackson Laboratory, stock #010802), which includes PG interneurons in the olfactory bulb (Fast & McGann, 2017; Wachowiak, Economo, Diaz-Quesada, Brunert, Wesson, White et al, 2013). These mice are on mixed backgrounds, though mostly C57BL/6 (per Jackson Laboratory development details).…”

“…In vivo optical imaging was performed (Czarnecki, Moberly, Rubinstein, Turkel, Pottackal, & McGann, 2011; Czarnecki, Moberly, Turkel, Rubinstein, Pottackal, Rosenthal et al, 2012; Fast & McGann, 2017; Kass, Czarnecki, Moberly, & McGann, 2017; Kass, Guang, Moberly, & McGann, 2016; Kass, Moberly, & McGann, 2013a; Kass, Moberly, Rosenthal, Guang, & McGann, 2013b; Kass, Pottackal, Turkel, & McGann, 2013c; Kass et al, 2013d) to visualize odor-evoked GCaMP signals from GAD65-expressing PG interneurons (Figure 1G–I) before and after conditioning (Figure 1A). Vapor dilution olfactometry was used during imaging (Czarnecki et al, 2011; Czarnecki et al, 2012; Kass et al, 2017; Kass et al, 2016; Kass et al, 2013a; Kass et al, 2013b; Kass et al, 2013c; Kass et al, 2013d) to present up to 3 concentrations of up to 5 monomolecular odorants that have no known innate valence.…”

“…Optical signals were analyzed as previously reported (Czarnecki et al, 2011; Czarnecki et al, 2012; Fast & McGann, 2017; Kass et al, 2017; Kass et al, 2016; Kass et al, 2013a; Kass et al, 2013b; Kass et al, 2013c; Kass et al, 2013d). Odor-evoked response amplitudes (ΔF/Fs) were quantified as the change in fluorescence during the first inhalation of odor and as the integrated change from baseline fluorescence during the 6-sec odor presentation.…”

“…PG interneurons integrate peripheral input from receptor-specific populations of OSNs with lateral information about other OSN populations (Aungst, Heyward, Puche, Karnup, Hayar, Szabo et al, 2003; Liu, Plachez, Shao, Puche, & Shipley, 2013) and also with top-down information from cortical and neuromodulatory structures (Boyd, Sturgill, Poo, & Isaacson, 2012; Eckmeier & Shea, 2014; Liu, Shao, Puche, Wachowiak, Rothermel, & Shipley, 2015; Ma & Luo, 2012; Markopoulos, Rokni, Gire, & Murthy, 2012; Shipley & Ennis, 1996). Notably, PG cell activity is influenced by interactions between the amygdala and locus coeruleus (LC) (Fast & McGann, 2017), which are both involved in emotional processes (Aston-Jones, Rajkowski, Kubiak, Valentino, & Shipley, 1996; LeDoux, 2000). Such modulation might enable PG cells to facilitate the detection of potentially threatening sensory cues.…”