Locus coeruleus

Accurate decision-making under imminent threat is critical to survival. However, arousal states, regulated by the neuromodulator norepinephrine, can cause both attentiveness and anxiety. Thus, adaptive decision making that scales with threat valence is crucial. To study proper decision-making under threat and the role of norepinephrine, we developed a novel task in which mice descend from a height toward an illusion of safe and unsafe visual cues. This virtual stimulus --- where there is a mismatch between actual safety and perceived safety --- relies on the evolutionarily conserved, innate fe

Noradrenaline (NA) is a ubiquitous neuromodulator largely produced by locus coeruleus (LC) neurons that impacts multiple cognitive processes. Non-invasive methods are used to track LC-NA activity. For instance, pupillometry is shown to be linked to arousal state, LC-NA, and other neuromodulator activity. However, given that pupillometry is a relatively slow process, the extent by which LC-NA can be predicted by pupil is limited. Since movements are linked with increased LC activity, orofacial movements could potentially be used as an additional psychophysiological marker for arousal and LC-N

Neuromodulation by the locus coeruleus (LC) plays a crucial role in cognitive processes related to learning, as well as memory consolidation (DOI: 10.1038/s41583-020-0360-9). Less is known about its role in memory retrieval. In this study, we explored this aspect following training of adult rats over a period of multiple days in an 8-arm radial maze to achieve robust spatial working memory (WM) and reference memory (RM) of the task. We then examined the consequence of patterned electrophysiological activation of the LC on the retrieval of recent (24h after the conclusion of training) or remote

Locus coeruleus (LC) activity consists in a sustained low-frequency firing rate (tonic activity), accounting for basal pupil diameter, interspersed with event-driven higher-frequency bursts (phasic activity), accounting for event-related transient changes in pupil diameter. Pupil size measurements are used here as a non-invasive biomarker of LC activity, and to assess its evolution with age. Pupil size was measured in 72 healthy participants (34 young: age = 23.0 years ± 2.6; 38 older: age = 69.3 years ± 6.8), who underwent a 2-minute passive gaze fixation task and a fast object categorization

Noradrenaline is released via volume transmission from axons originating in the locus coeruleus and released into the parenchyma to be detected by both neurons and astrocytes. Noradrenergic α-1 receptors are Gq-coupled receptors that induce intracellular calcium release from the endoplasmic reticulum as a key pathway for astrocyte calcium signalling. Due to interactions between astrocytes and synapses including their known roles in structural isolation of synapses, metabolic support, potassium buffering and gliotransmitter release, fluctuations of intracellular calcium in astrocytes can influe

Our attention falters, which is commonly known as ‘attentional blink’ (AB), after spotting a target; as a result, the subsequent target often goes unnoticed. Attentional demand also affects the size of the pupillary aperture. In previous studies, differential pupillary dilation averaged across trials within a short critical epoch distinguished AB. In contrast, we examined the pupil dynamics on a trial-by-trial basis. Healthy young volunteers performed a task, wherein two visual targets embedded in a series of distractors were presented in a rapid succession. The participants were asked to iden

Noradrenergic (NA) neurons originating from the locus coeruleus (LC) serve as the primary source of noradrenaline in the brain and play a critical role in arousal and cognitive functions. Previous studies have shown a potential link between astrocyte activity in the LC and emotional dysfunction, and suggested that astrocytes may influence NA neuron activity by modulating extracellular ion and neurotransmitter concentrations or by releasing gliotransmitters. However, there is currently no evidence for direct communication between astrocytes and NA neurons in the LC. In this study, we addressed

…the noradrenergic (NA) neurons in the locus coeruleus (LC) and the parvalbumin (PV)-positive cortical interneurons are involved in the regulation of sleep spindles. However, the interplay o

The brainstem locus coeruleus (LC) is the sole source of noradrenaline in the neocortex, hippocampus and cerebellum. Noradrenaline (NA) is a neuromodulator involved in the regulation of excitability of brain networks. In this study, we investigated whether chemogenetic activation of the LC is able to induce hippocampal noradrenaline release and affects hippocampal excitability.Male Sprague Dawley rats (n=8) were injected with the viral vector CAV2-PRSx8-hM3Dq in the LC for expression of hM3Dq, which allows chemogenetic LC activation upon systemic injection with deschloroclozapine (DCZ). Rats w

…attributed to maladaptive activity of locus coeruleus (LC), the main source of forebrain NA. Our lab recently uncovered a role for dysregulated LC-NA function in motor learning delays of the 16p11.2 deletion (+/-) mouse-model of ASD. We found that reduced NA levels in primary motor cortex (M1) caused delays in motor learning and increased neuronal activity in M1 pyramidal neurons. Both behavioral and neuronal phenotypes were rescued by chemogenetic activation of LC-NA. We next

Learning whom to trust is an important social skill, which can be affected by aging and loneliness. An often-used experimental task to study trust learning is the repeated trust game (Berg et al., 1995) where participants repeatedly invest money in another player who can be trustworthy – or not. 50 healthy, neurotypical older adults (64 to 84 years) and 62 younger adults (age: 20 to 33, see Sladky & Riva et al., 2022) played the repeated trust game (Figure 1a) while undergoing 3T functional MRI. We found that trust learning was impaired in older adults, particularly in those who reported h

Orexin neurons originate in the lateral hypothalamus, receive many inputs, and project throughout the brain. This puts them in an ideal position to integrate large amounts of information and signal them toward desired targets. We hypothesized that arousal, which impacts a variety of internal states and behaviours, could be one of these signals that orexin neurons transmit. To test this, we investigated the causal and correlative links between orexin neurons and pupil size, which is often taken as a readout of arousal. Optogenetic stimulation, 2-photon imaging, photometry, ablation, and pharmac

Locus Coeruleus (LC) is a neuromodulatory system that is heavily affected at an early stage of Alzheimer´s Disease (AD) progression. In human AD patients, the LC shows an extensive loss of neurons. Therefore, the goals of this project are to examine the influence of the LC on HPC-dependent mnemonic processes and on their impairment in AD. To achieve this, we explored, whether the structural and functional connectivity between the LC and the HPC is altered in an APPswe/PSEN1dE9 mouse model of AD. We found a significant reduction of LC to HPC projections identified by immunohistochemically stain

…release of noradrenaline (NA) in the locus coeruleus (LC) and serotonin (5HT3) in the raphe nuclei (RN). For this purpose, male Wistar rats were used, t

The delayed non-match to position task (DNMTP) is a translational instrumental learning paradigm commonly applied preclinically to assess higher executive functions including attention and working memory in rats. In this study, the effects of acute inflammatory challenges were assessed on cognitive performance in the DNMTP task.. Male and female Wistar rats were trained to criteria on the task. Initially, in validating the test, the effect of treatment with the muscarinic receptor antagonist scopolamine (0.02mg/kg, s.c.), known to disrupt performance in the task, was confirmed. Sex differences

…Among these, the Locus Coeruleus (LC) belongs to the primary brain areas that show such malfunctions in the early stages of AD. The LC generates large noradrenaline (NA) signals that are key for the architecture of sleep in mice. In contrast, how LC malfunctions relate to sleep disturbances in AD remains unknown.We explore the real-time functionality of the noradrenergic system during AD’s prodromal phase in an established A

…(TH+) neurons in the locus coeruleus (LC) and the ventral tegmental area (VTA), and increase noradrenaline (NA) and dopamine (DA) release in the dHPC. This raises th

…Interestingly, the locus coeruleus (LC) that contains the highest density of noradrenergic neurons in the brain, is among the brain stem areas first displaying Lewy bodies in the disease, and is associated with prodromal non-motor symptoms. Despite its small s

Noradrenergic (NA) neurons in the locus coeruleus (LC) play a critical role in behavior by supplying norepinephrine to the brain. Understanding how LC-NA neurons are regulated is essential to understanding the role of the LC-NA system in behavior. Since previous studies have identified a population of inhibitory pre-LC neurons that regulate LC-NA neurons, this study investigates whether there are excitatory pre-LC neurons responsible for the regulation of LC-NA neurons. We infused AAVs into the LC of TH-Cre crossed with vGluT2-FLP mice expressing wheat germ agglutinin (WGA) and eYFP in a Cre-

…somatosensory responses by the locus coeruleus (LC), a key brainstem nucleus that plays a critical role in many cognitive and physiological functions. Previous electrophysiological investigations have revealed a diminished ability of the LC to inhibit somatosensory responses in the caudal nucleus of the trigeminal nerve (Sp5C) of diabetic mice. The administration of noradrenaline ag

Moment-to-moment fluctuations in neuromodulatory brainstem arousal systems (e.g., dopamine and noradrenaline systems) can show large effects on learning and memory. Dopaminergic projections to the hippocampus play an important role in the formation of long-term memories. For example, previous studies have employed a reward anticipation manipulation during memory formation, eliciting dopaminergic responses in the midbrain and subsequently enhancing the encoding of memories. Until now, the origin of these dopaminergic projections has been attributed to the ventral tegmental area/substantia nigra

…The Locus Coeruleus (LC) is one of the first areas to exhibit Lewy bodies and neurodegeneration. Its dysfunction is associated to the appearance of nonmotor symptoms due to its noradrenergic (NA) projections and influence on the homeostasis of

While the interconnection of monoaminergic nuclei, namely the Raphe nucleus, Locus coeruleus (LC) and Ventral Tegmental Area (VTA) is widely acknowledged for its pivotal role in mediating diverse cerebral functions, the true complexity lies in the nuanced neuroanatomical and neurochemical diversity within each system. Recent discoveries have brought to light distinctive neuronal populations within the raphe nucleus or the LC, both projecting specifically to the VTA, main nucleus for dopamine secretion. The raphe nucleus is a neurochemically diverse hub, hosting not only serotonergic neurons bu

Spinal cord injury immediately impairs movement control and other essential physiological functions. Evidence has shown that a large-scale network including spinal and supraspinal structures is recruited after SCI to promote functional recovery. Orexins (hypocretins), known for promoting wakefulness, arousal, and reward-seeking behaviours, also influence muscular tone, locomotion initiation, and skilled performance, exerting a multi-systemic effect on motor control predisposing for movement execution. Despite the potential relevance of orexin transmission in motor recovery after CNS damage, th