UC Riverside

The locus coeruleus (LC) is a small nucleus situated in the pons of the brainstem, comprised of less than 20,000 neurons in the adult human brain. Neurons in the LC broadly innervate the brain and release the neuromodulator norepinephrine (NE) at their terminal field. NE, a neurotransmitter commonly associated with stress, acts on both post- and pre-synaptic adrenergic receptors to alter cellular and circuit function. LC neurons also exhibit distinct morphological and neurochemical differences that contribute to a heterogeneous cellular distribution within the nucleus. Notably, this heterogeneity in the LC, as well as heterogeneity in adrenergic receptor distribution, suggests that the LC-NE system is capable of differential modulation of downstream areas. Accordingly, the LC-NE system has long been recognized as critical in mediating a wide spectrum of brain functions ranging from sleep-wake transitions and arousal to higher-order processes such as attention and learning. Clinically, this modulatory system is implicated in attention-, stress- and anxiety-related disorders, including attention-deficit hyperactivity disorder (ADHD) and post-traumatic stress disorder (PTSD). Decades of research has made tremendous progress toward revealing LC-NE functions, but our knowledge of the fundamental neurobiology underlying how the LC-NE system affects the activity of downstream neurons and modulates behavioral states and cognition is still incomplete. To bridge these gaps, we present three distinct research questions focused on the role of LC in sensory related behaviors and on the LC-pupil relationship. First, we explore how LC affects whisker sensory perception through bidirectional perturbations of the nucleus during a sensory behavior task. We then assess how LC contributes to behavioral flexibility using electrophysiology and optogenetic perturbations in a novel behavior task. Finally, we test the relationship between LC and pupil diameter, to determine the extent to which pupil can be used as a non-invasive measure of LC spiking in real-time. Together, these research studies help elucidate the involvement of LC in various sensory-related behavioral processes. It is our hope that these findings will further our understanding of the LC, as well as the diseases and disorders associated with this neuromodulatory nucleus.