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Results for “Locus Coeruleus”

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PubMed2025

A comparison of viral strategies and model systems to target norepinephrine neurons in the locus coeruleus reveals high variability in transgene expression patterns.

The locus coeruleus (LC) norepinephrine (NE) system is involved in a variety of physiological and pathophysiological processes. Refining our understanding of LC function largely relies on selective transgene expression in LC-NE neurons, allowing targeted manipulation and readout of noradrenergic neurons. Here, we performed a side-by-side comparison of the most commonly used strategies to genetically target the LC, including different cre driver lines and promoter-mediated transgene expression. We report differences between these strategies in terms of transgene expression efficacy and specificity. Parallelly, we found no behavioral alterations in cre-expressing mice of any mouse line compared to wild-type littermates. Finally, to further facilitate the investigation of LC-NE function, we created a suite of constructs, including a reporter protein, a calcium indicator, and a light-driven cation channel, whose expression is mediated by the previously described PRS×8 promoter. These constructs allow identification, monitoring, and manipulation of LC-NE activity either in wild-type mice, or in combination with tissue-specific manipulations of different cre driver lines. The results of our study are crucial for the interpretation of previous experiments using the respective targeting strategies, as well as for the design of future studies.

Animals↗
PubMed2026

Locus coeruleus activation transforms cortical taste representations.

Noradrenergic neurons in the locus coeruleus (LC) shape sensory processing, yet how LC activity influences population taste coding remains unclear. Using optogenetic LC activation with miniscope imaging in the gustatory cortex (GC), we examined LC modulation of multiple taste attributes. Phasic LC activation strengthens correlations between neuronal responses and palatability and expands the dynamic range of stimulus representations along a palatability axis. This expansion is driven by an aversive shift in the representations of all tastants except sucrose, the most palatable stimulus. For mixture ratio and concentration, phasic activation expands and rotates attribute axes, potentially reflecting dependencies between these attributes and palatability. These transformations likely arise from multiplicative gain modulation and more flexible tuning changes. Tonic LC activation affects fewer neurons and does not expand attribute axes. Together, the findings show that LC activation reorganizes GC population geometry in a pattern-dependent manner, linking neuromodulation with feeding behavior and affective processing.

CP: neuroscience↗
PubMed2026

Intra-locus coeruleus LPS administration induces anxiety-like behavior, thermal hyperalgesia, and striatal lysosomal alterations: Relevance to Parkinson's disease.

According to Braak's staging hypothesis, Parkinson's disease (PD) pathology may originate in extranigral regions, including the locus coeruleus (LC). In parallel, PD has been associated with lysosomal dysfunction. Here, we investigated whether intra-LC lipopolysaccharide (LPS) injection may produce behavioral alterations and lysosomal protein changes in the striatum and prefrontal cortex (PFC), regions critically implicated in PD pathology. Adult male Wistar rats received unilateral injections of saline or LPS (10 µg/2 µL) into the LC or striatum and were assessed for anxiety-like behavior, thermal hyperalgesia, and motor coordination. A separate cohort was sacrificed 15 days post-injection to assess lysosomal proteins (cathepsin D, β-glucocerebrosidase, Lysosomal Associated Membrane Protein 2 (LAMP2)) and α-synuclein (α-Syn). Intra-LC LPS induced anxiety-like behavior, reflected by reduced time spent in the center of the open field, and thermal hyperalgesia, as shown by shortened tail-flick latency, whereas intra-striatal LPS impaired locomotion and motor coordination, evidenced by reduced line crossings and decreased rotarod performance. Intra-LC but not intra-striatal LPS reduced LAMP2 levels in the striatum, while all other markers remained unchanged in both regions. These findings provide experimental support for Braak's hypothesis.

Animals↗
PubMed2025

The locus coeruleus influences behavior by coordinating effective integration of fear memories and sensory input.

An essential function of memory is to guide behavior for better survival and adaptation. While memory formation has been extensively studied, far less is understood about how memory retrieval influences behaviors. In the auditory Pavlovian threat conditioning paradigm using C57BL/6J mice, retrieving a conditioned threat memory is associated with spiking in two dorsomedial prefrontal cortex (dmPFC) neurons with transient (T-neurons) and sustained (S-neurons) patterns. We show here that T-neurons and S-neurons are two distinct neuronal populations with different neuronal and synaptic properties and mRNA profiles. S-neuron spiking matches freezing behavior and is required for freezing. This sustained activity in S-neurons requires auditory inputs and the release of norepinephrine (NE) in the dmPFC. The activation of the locus coeruleus (LC) is initiated by dmPFC T-neuron inputs, sustained by auditory inputs, and is required for the transition to freezing by enhancing S-neuron activity. Interestingly, LC activation precipitates a brief period during which nonconditioned cues also induce freezing. Our findings highlight the critical contribution of the LC/NE system in the transition from memory to behavior, which coordinates the effective integration of memory, sensory inputs and emotional state for optimal adaptation.

Animals↗
PubMed2025

Stress reactivity is modulated by cannabinoid type-1 receptors in norepinephrine and epinephrine neurons in a context-dependent manner.

Disruptions in the endocannabinoid system (ECS) and norepinephrine/epinephrine (NE/E) system are individually linked to stress-related neuropsychiatric disorders, but their interaction in shaping stress responses remains unclear. We investigated the role of the ECS's primary receptor, cannabinoid type-1 receptor (CB1R), in NE/E-producing neurons using anatomical, behavioral, and physiological analyses in a conditional knockout mouse model (Cnr1cKO-Dbh), in which the Cnr1 gene-encoding CB1R-was selectively deleted in dopamine beta-hydroxylase-expressing cells. In situ hybridization in control mice revealed Cnr1 is broadly expressed in medullary C1/A1 and C2/A2 and sparsely in the locus coeruleus, marking the first cell-type-specific characterization of Cnr1 in brainstem catecholaminergic populations. Cnr1 was reduced across all nuclei in Cnr1cKO-Dbh mice, confirming targeted deletion. Behaviorally, Cnr1cKO-Dbh mice showed normal baseline anxiety-like behavior, but reduced avoidance in the open field after acute restraint stress. However, no genotype differences were found after foot shock in the elevated plus maze and light-dark box, suggesting context-dependent CB1R effects. Cnr1cKO-Dbh mice also exhibited reduced immobility in the forced swim test, but not the tail suspension test. In response to looming visual threats, they showed increased escape behavior across trials, reduced rearing and exploration during the first disc presentation, and no changes in freezing. Heart rate responses following foot shock stress were unchanged. These findings suggest that CB1R in NE/E neurons selectively modulate components of the acute stress response in a manner dependent on behavioral context. This work underscores the need for further investigation into the circuit- and state-specific roles of CB1R signaling in stress regulation.

Animals↗