Optogenetic stimulation

…Also, while BG stimulation can bias choices, in

Phasic dopamine (DA) release plays a major role in learning by assigning incentive value to associated stimuli. A leading theory proposes that this process is analogous to a reinforcement learning algorithm called temporal difference (TD) learning, and that DA acts analogously to the reward prediction error (RPE) term within the TD algorithm. TD assigns reward predictions (values) to states by learning not only from rewards but also when its internal value estimates change, requiring an approximate temporal derivative calculation. Although many studies have demonstrated similarities between DA

Brain networks communicate through anatomical connections which are thought to mediate flexible, state-dependent interactions. We call the resulting pattern of communication “effective” or “functional” connectivity. In the motor system, within-day learning may rely primarily on modulation of networks, although the source of this modulation is unclear [1]. Over longer timescales, changes in anatomical connectivity can shape behavior through processes like Hebbian plasticity [2]. Understanding how these mechanisms combine to shape learning will require measurements of anatomical and functional c

…combine spatiotemporally precise optogenetic stimulation at cellular resolution to manipulate neuronal states in the network with optical imaging of fluorescent genetically-encoded indicators for simultaneous readout of neuronal activity [1, 2]. The biophysical models of various optogenetic tools have been studied computationally in single neurons, accurately fitting experimental data [3, 4]. However, the effects of optoge

…the causal relationship between stimulation and restoration of function is

In-vivo measurements are inherently hampered by the motion of behaving animals, particularly in case of using voltage sensitive dyes when the signal is acquired from small regions of interest to get the maximal temporal precision. Here we present an FPGA-based, clearly acousto-optical 3D online motion correction for signal extraction on high temporal resolution of 100 kHz on a volume of 500x500x400 um up to 100 Hz of motion with a residual motion under 1 um at proper signal-to-noise ratio. The correction can be combined with all scanning modes, including point-scan, squared- and ribbon-based s

…that mice can be trained to report optogenetic stimulation of primary somatosensory cortex (S1), bypassing the trial-by-trial perceptual variability associated with external stimuli. These studies, however, stimulated different populations of S1 neurons on different trials which may also contribute to perceptual variability. Our aim is to use spatial light modulation (SLM) to stimulate the same S1 n

…Currently available tools like optogenetics and chemogenetics affect the entire astrocytic population, making it difficult to target specific subsets. This lack of specificity hinders our understanding of the role of astrocytes in behavior.We present a tool to translate the activity-mediated calcium signals of astrocytes into gene expression in a light-dependent manner, i.e. AstroLight. Using AstroLigh

For the long term aim to develop a visual cortical prosthesis, optogenetic stimulation of primary visual cortex (V1) provides a more specific alternative to electrical stimulation. However, adoption of optogenetic techniques from rodents to macaques as an intermediate step towards humans has proven to be challenging. Here we present prelimnary results, directly comparing effects obtained from optogenetic vs electrical stimulation of macaque V1.We injected AAV9-CamKIIa-ChrimsonR-mScarlet-KV2.1 into macaque V1 under electrophysiological guidance. We first investigated neural activity in response

…Optogenetic stimulation, 2-photon imaging, photometry, ablation, and pharmac

The ability to learn and adapt precise motor programs in a changing environment is crucial for animal survival. A prominent theory suggests that the cerebellum utilizes forward models to compare perceived sensory stimuli (perceived reafference) with predictions based on past experiences (expected reafference), quickly adjusting motor programs to environmental changes. Utilizing a new mouse behavioral paradigm involving sensorimotor perturbations in a simple joystick pulling task, we can decipher the role of the cerebellum in rapid motor adaptation. Previous results revealed parasagittal bands

Although the aetiology of schizophrenia is still not thoroughly understood, post-mortem studies of patients have consistently revealed alterations of GABAergic interneurons, particularly lower levels of GAD67 and parvalbumin in cortical parvalbumin interneurons (PVs). A deficient maturation of PVs could relate to the neurodevelopmental aspect of schizophrenia since normal wiring of cortical circuits relies on this process. We have previously shown that mice with an early postnatal NMDA receptor ablation in corticolimbic GABAergic interneurons –predominantly PVs– present schizophrenia-like phen

The optical cochlear implant (oCI) utilizes optogenetic stimulation of the spiral ganglion neurons (SGNs) in the cochlea to improve hearing restoration. Preclinical data has shown that this may improve bionic hearing in CI users by targeting smaller areas of the cochlea compared to electrical stimulation.This study investigates the influence of the light emitter characteristics (one/two laser-coupled glass fibers) on the spread of excitation, through a combination of computer simulations and in-vivo multiunit recordings of inferior colliculus activity in Mongolian gerbils that postnatally rece

Cognitive processes underlying behavior such as navigation, attention, and perception are linked to specific spatiotemporal patterns of neural activity in the neocortex. These patterns arise from synchronous synaptic activity and are often detected in particular frequency bands in the cortical field potential. However, cortical activity is highly variable on multiple timescales (milliseconds to hundreds of seconds). Identifying discrete neural events underlying patterned activity within highly dynamic cortical network fluctuations thus remains a critical challenge. Here, we develop a novel ana

Food sensory perception has emerged as a potent regulator of specialized feeding circuits; yet, the consequences on feeding behaviour and the underlying neuronal basis remain poorly understood. Here, we reveal a sensory pathway that coordinately integrates food odours to control forthcoming nutrient intake. Unbiased whole-brain mapping of food odours-induced brain activity revealed a potent activation of the medial septum (MS), where food odours selectively activate MS glutamatergic neurons (MSVGLUT2). Characterization of the activity dynamics of MSVGLUT2 neurons uncovered a biphasic modulatio

We developed an optogenetic tool InLOV that allows for specific activation of the insulin receptor signaling pathway. Light-activation of InLOV drives insulin induced neuronal plasticity in the mouse cerebellum and improves cerebellar driven self-motion behavior. Thus, InLOV opens the opportunity to modulate the insulin signaling pathway by optogenetic stimulation throughout the whole body and to develop new therapeutic strategies for pathologic insulin signaling.

Generalised and focal to bilateral convulsive seizures are risk factors for Sudden Unexpected Death in Epilepsy (SUDEP). Postictal generalized EEG suppression (PGES), a generalized flattening of the scalp EEG, is a potential marker of increased seizure severity and risk of SUDEP. PGES has been variably linked to autonomic dysfunctions including loss of arousal. Risk of SUDEP may be increased in direct proportion to duration of PGES and loss of arousal. Convulsive seizures can co-exist with spreading depolarisation (SD), a slowly propagating wave of neuronal and glial depolarisation (typically

Neurovascular coupling (NVC), the tight coupling between neural activity and cerebral blood flow (CBF), is essential for brain function and integrity. Decreased CBF and altered NVC are among the earliest biomarkers of Alzheimer’s disease (AD) and may exacerbate its progression. Among the various cellular players of NVC, cyclooxygenase-2 (COX2) pyramidal cells, play a key role via the release of prostaglandin E2 (PGE2), which can bidirectionally control the NVC. We investigated the role of pyramidal cells in neurovascular uncoupling of AD using cortical slices from triple transgenic mice expres

The Dorsal Raphe Nucleus (DRN) is the largest of the serotonergic nuclei, but it also comprises a wide variety of neuronal subpopulations, including dopaminergic cells (DRNDA) and astrocytes, which may represent a source of local DRN modulation. The DRN participates in a wide range of behavioral responses related to the processing of aversive stimuli, leading to anxiety state. While the role of DRN5-HT and DRNDA in valence processing is emerging, the contribution of DRN astrocytes (DRNAstro), as well as the underpinning cellular mechanisms, remain elusive. Unpublished data from the lab indicat

In mammals, circadian rhythms are controlled by the central clock, suprachiasmatic nuclei (SCN) in the hypothalamus. The external light signal could entrain SCN through intrinsically photosensitive retinal ganglion cells (ipRGCs), a type of neuron in the retinal of mammalian eyes, by releasing glutamate. The innervation of ipRGCs to SCN has been revealed by using genetic tracing techniques and contributes to the synchronization of the circadian rhythm. SCN is a heterogenous structure that contains different neurons, while AVP and VIP neurons are critical for the networking of circadian rhythm.

The medial prefrontal cortex (mPFC) is a brain region responsible for a variety of cognitive functions including attention and working memory. Cholinergic neurons, which release acetylcholine (ACh), are known to enhance attention and their pathophysiology is associated with disorders such as Alzheimer’s disease and epilepsy. Nicotinic acetylcholine receptors (nAChRs) are activated by the cholinergic system and modulate neuronal excitability. Therefore, understanding nAChR mediated synaptic neurotransmission will allow us to better understand how the activity of neurons are precisely controlled

The involvement of the Enteric Nervous System (ENS) in digestive and neurological disorders is widely recognized and constitutes a novel target for diagnostic biomarkers and therapies. For example, Parkinson’s disease patients are now stratified according to gut-first or brain-first patterns that diverge in symptom progression. However, large-scale characterization of this neuronal network is often limited to local sampling that cannot reflect network dynamics. We present a new method for minimally invasive in-vivo intraluminal investigation of electrophysiological activity from the entire dis

…As it was recently discovered thatoptogenetic stimulation of the rostral PPN can induce full body motor arrest, we wanted to investigateif this behavior was limited to motor output, or if sensory input was halt

…We discovered that optogenetic manipulation's impact varied with the animal's past decisions. Notably, trials following the same choice were less influenced by optogenetic stimulation, suggesting a form of neural adaptation or memory effect within the circuit. Our analysis shows distinct activity patterns in the