Optogenetic activation

How does a cat gracefully walk and suddenly freeze when spotting a mouse? In this talk, we look at how networks in the spinal cord generate movement. In particular, we address the fundamental yet poorly understood question of motor control: How can rhythmic movements, such as walking, be generated and stopped at any point in the cycle while posture is preserved? Since conventional models of spinal motor function rely on alternation between flexor and extensor modules, which are limited to just two phases, this question exposes the essential shortcoming of the conventional understanding: How ca

…affects mouse performance via optogenetic activation of the Dorsal Raphae nucleus (DRN). We show that it is necessary to account for the complexity of behavioral variability across mice in order to uncover the strategies mice deploy to perform the task and how serotonergic neuromodulation affects behavior. While most studies have quantified decision-making perfor

The anterior cingulate cortex (ACC) is important for both sensory integration and the processing of affective aspects of pain to coordinate appropriate behavioral reactions. However, the role of the projections of ACC neurons to subcortical areas and their influence on sensory processing are not fully understood. Here, we identified that ACC neurons preferentially project to the contralateral claustrum (CLA). Extracellular recordings in awake mice showed that ACC neurons projecting to the contralateral claustrum (ACC→contraCLA) preferentially respond to contralateral mechanical sensory stimula

The globus pallidus externa (GPe) is a basal ganglia structure with a high content of astrocytes compared to neighboring brain regions. Apart from its well-known role in locomotor behavior, recent studies showed that the GPe is also involved in cognitive functions, motivated behavior and sensory integration. The vast majority of studies has focused on neuronal subpopulations in GPe, while the function of the numerically superior astrocytes remain elusive. Recently, we showed that astrocytes in GPe express dopamine D2 receptors (D2Rs), and their selective manipulation can have profound effects

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

…are activated by nicotine and their optogenetic activation is reinforcin

Fettah Abderrahman1, Boulain Marie1, Guilhemsang Lise2, Juvin Laurent1, Mallet Nicolas2, Barrière Grégory1 The intricate orchestration of motor control is governed by the cortico-basal ganglia- thalamocortical loops, with recent investigations highlighting the pivotal role of basal ganglia downstream projections to pedunculopontine nucleus (PPN) in regulating specific motor programs. Despite these advancements, the precise mechanisms through which the basal ganglia networks selectively control these functional motor modules remain incompletely elucidated. Our findings in mouse reveal that th

In environments rich with complex multisensory stimuli, flexible and effective behaviors rely on our ability to transfer learned associations across sensory modalities. Here, we explored the intertwined cortical representations of whisker and visual sensations in mice, focusing on their role in cross-modal transfer learning. Mice trained to differentiate between the stimulations of two vertically-aligned whiskers could seamlessly transfer this learned behavior to distinguish between two visual stimuli based on their vertical positioning. Generalization was achieved only when the spatial reward

Accumulating evidence shows that dopaminergic neurons of the ventral tegmental area (VTA) are crucial for rewarding and aversive responses. The activity of these neurons is intricately regulated by various neuropeptides, one of which is the endogenous opioid dynorphin. It is thought that the main source of dynorphin in the VTA arises from nucleus accumbens (NAc) D1-MSNs, and that dynorphin acts primarily on kappa opioid receptors (KORs), serving as negative feedback mechanism to modulate dopamine release. Thus, dynorphin signals may regulate dopamine dynamics and, in this way, contribute for r

Naturalistic behaviors in mammals are triggered by specific sensory cues and strongly influenced by internal states such as hormonal levels. Infant-oriented motor actions in maternal mice are enabled by sensory stimuli from the pups (such as vocalizations, somatic touch). Some maternal behaviors, like nursing and searching for isolated pups outside of the nest, further depend on the release of the hypothalamic neurohormone oxytocin (Menon & Neumann, 2023). However, pup stimuli are often aversive to virgin females (Lecca et al., 2023; Schiavo et al., 2020), who also exhibit different patter

The deep layers (V/VI) of the entorhinal cortex constitute a major relay station for routing neuronal activity from the hippocampus to downstream networks. To identify contributing pathways, we recently investigated the structural and functional organization of hippocampal projections to layer V (LV) of the medial entorhinal cortex (MEC) (Ohara, Rannap et al., Cell Rep. 2023). Here, we performed whole-cell patch-clamp recordings from MEC-LVI neurons combined with field potential recordings from hippocampal area CA1 in horizontal mouse brain slices. We found that a spontaneously occurring hippo

Mammalian reproduction is highly energy intensive, and requires an animal to prioritize feeding or sociosexual interaction, depending on need and opportunity. We have recently shown that two leptin-sensitive populations – leptin receptor-expressing (LepRLH) and neurotensin-expressing (NtsLH) neurons of the lateral hypothalamus – act in a complementary manner to enable resistance to hunger and gate the pursuit of social needs (Petzold et al., Cell Metab 2023).Currently, using single-cell Ca2+ imaging in freely moving mice, we found that LepRLH neurons not only preferentially encoded conspecific

…similar to hibernation, through the optogenetic activation of Q neurons. These neurons, known for producing pyroglutamylated RFamide peptide (QRFP), and localized in the anteroventral periventricular nucleus (AVPe) have been previously shown to induce a hibernation-like, hypometabolic state when excited. Our approach utilizes a 10µW optogenetic stimulation of OPN4dC, specifically targeting the AVPe of QrfpiCre/+ mice, to activate Q neurons and induce a state we term optogenetic QIH (Q neuron-induced hypometabolis

Recent data show that a significant fraction of cortical pyramidal neurons has an axon originating from a basal dendrite (axon-carrying dendrite, AcD) rather than from the soma. In the rodent hippocampus, these AcD cells convey privileged synaptic excitation especially in network states with strong perisomatic inhibition (Hodapp et al., 2022). We have recently shown that hippocampal AcD cells receive stronger commissural input than neurons with somatic axon origin (non-AcD) (Stevens et al., 2023).AcD cells are also present in the neocortex, though seemingly less frequent than in the hippocampu

Standard models of episodic memory emphasise that parallel streams of spatial information, arriving from medial entorhinal cortex (MEC), and object information, arriving from lateral entorhinal cortex (LEC), are integrated within the hippocampus. However, we recently discovered that fan cells in the LEC send direct projections to MEC, suggesting that spatial and object information could be integrated within MEC (Vandrey et al. 2022, doi:10.7554/eLife.83008). Evidence for object-related firing in the MEC is consistent with this possibility, but whether LEC projections influence spatial and obje

…Optogenetic activation of these neurons at theta frequencies (4-12 Hz) entrains hippocampal theta oscillation and sustains locomotion outlasting the stimulus duration. However, the specific cellular and circuit mechanisms responsible for initiating and sustaining MS VGluT2-driven persistent locomotion and associated hippocampal theta oscillations remain unclear. To address these questions, we optogenetically targeted glutamatergic neuro

Obsessive-compulsive disorder (OCD), a disabling and notoriously treatment-resistant neuropsychiatric disorder that affects 2-3% of the general population, is characterized by reoccurring, intrusive thoughts (obsessions) and repetitive, ritualistic behaviors (compulsions). Although OCD has long been associated with dysfunction within the cortico-striato-thalamic-cortical circuits, the thalamic role in OCD pathogenesis is highly understudied in the current literature. Here we identified a rat thalamic nucleus – the reuniens (NRe) – that mediates persistent, compulsive self-grooming behaviors. O

…study, we investigated the role of optogenetic activation of the direct pathway in its ability to reestablish motor function and regulate oscillatory activity in cortex-basal ganglia loops. Rats received a unilateral injection of 6-OHDA into the medial forebrain bundle, followed by the delivery of adeno-associated viruses (AAVs) that specifically transduced Dopamine-1-Receptor-positive medium spiny neurons (DRD1-neurons). Using th

…We studied the effects of unilateral optogenetic activation of PRF inhibitory cells (PRF/G

…it remains unknown how noradrenergic activation translates into subsequent glial calcium waves and provokes motor arrest. Our working hypothesis is that noradrenergic neurons integrate intensive s

The locus coeruleus (LC) is the primary source of norepinephrine in the brain and is known to modulate brain-wide arousal state. Recent evidence suggests that it also regulates immediate attentional responses by modulating the gain or reset of downstream cortical networks to optimize behavioral outcomes. Accordingly, cortical regions of high cognitive function, such as the medial prefrontal cortex (mPFC), are thought to directly influence LC output for this purpose. However, physiological evidence for monosynaptic connections between mPFC and LC neurons and their properties are still limited.

When awake, we perceive stimuli from the external world. When asleep, our brain disconnects from the sensory environment. In contrast to these exteroceptive stimuli, little is known about how interoceptive stimuli are processed by the sleeping brain. The vagus nerve is a mixed sensory-motor nerve that interfaces between the autonomic periphery and the brain. We asked whether stimulating specifically vagal sensory afferents modulates sleep. All experiments are based on viral transfection of vGluT2-expressing neurons in the jugular-nodose ganglion of the left vagus nerve, in combination with pol

Despite the well-demonstrated modulatory effect of serotonin on spinal motor circuits, the specific roles and identity of the involved serotonergic neurons remain unclear. This ambiguity owes to the anatomical and neurochemical heterogeneity of the medullary brainstem regions housing the spinally-projecting serotonergic neurons, and to the limited number of studies investigating their connectivity and function cell-specifically.Here, we selectively target the midline serotonergic neurons of the caudal medulla (mCM-5HT) in the mouse to explore their output connectivity in the spinal cord and th

…Therefore, we aimed to explore how optogenetic activation (priming) of the HIP-mPFC pathway can facilitate object-location memory in adult and aging mice. For this purpose, we injected mice