Neuronal activity

…to intracranially record and stimulate neuronal activity within precisely localized brain structures, enabling high-impact human neuroscience investigations. This NOFO seeks exploratory research projects, from newly formed or established multi-disciplinary teams, to understand how dynamic activity of single cells and ensembles of neurons in spatially organized networks gives rise to the internal states we experience as sensations, perceptions, emotions, thoughts, and memories, and to observable motor and social behaviors. The

Neuroplasticity is essential for the establishment and strengthening of neural circuits. Repetitive transcranial magnetic stimulation (rTMS) is commonly used to modulate cortical excitability and shows promise in the treatment of some neurological disorders. Low intensity magnetic stimulation (LI-rTMS), which does not directly elicit action potentials in the stimulated neurons, have also shown some therapeutic effects, and it is important to determine the biological mechanisms underlying the effects of these low intensity magnetic fields, such as would occur in the regions surrounding the cent

Spatiotemporal patterns of neuronal activity are hypothesized to be essential for information processing in the brain. They suggest the existence of cell assemblies, groups of co-active neurons that represent a distinct cognitive unit, potentially related to specific behaviors or representations. Conventionally, cell assemblies are defined by strong structural connections, such that the stimulation of a portion of its members should transiently activate the entire assembly. Their exact composition and computational role, however, have yet to be fully clarified. We present the detection of spik

A fundamental problem in neuroscience is how neuronal activity in the brain generates organized and stable behaviors across multiple timescales. Recent research in many model organisms, e.g. in monkeys, led to the observations that the neuronal encoding of individual actions, such as preparation for and execution of arm movements, is achieved by large neuronal populations but often lies on low-dimensional manifolds. However, it is largely unclear if such manifolds also coordinate higher dimensional activity patterns that correspond to simultaneously executed fine-tuned movements. In order to a

Differentiation of human induced pluripotent stem (hiPS) cells into three-dimensional neural organoids is already enabling access to key developmental processes in the human nervous system and offers an opportunity to model severe neurological disorders. Our laboratory has pioneered the use of instructive signals to derive regionalized neural organoids. Automation for high-throughput generation of these neural organoids could facilitate drug and genetic screening applications, especially if amenable to arrayed production. Here, we develop a platform relying on inexpensive equipment for automat

…have started to investigate the neuronal underpinnings of mouse binocular vision. However, to our knowledge, no systematic investigation of whether mice experience binocular rivalry-like perception when presented with binocularly conflicting stimuli exists. Here, we recorded neuronal ac

…pulsations can directly modulate neuronal activity within the central nervous system via baroreceptive transduction. We recorded local-field-potentials (LFP) within the rat olfactory bulb (OB) using a semi-intact, perfused nose-brain preparation, while monitoring the pressure pulsations induced by the peristaltic perfusion pump that in our setup operated within the physiological range of hea

Individual response to stressful events varies greatly and can impact behavioral and neurological outcomes. Depending on intrinsic and extrinsic factors, active, passive, or maladaptive coping behavior can emerge in the same subject when exposed to different stressors. Rodent stress models such as Learned Helplessness (LH) and Social Defeat Stress (SDS) have been used to uncover a stressor’s impact on behavior and the underlying brain changes. In LH, mice subjected to inescapable shocks can have inappropriate passive behavior or “helplessness”, or continue to exhibit normal escape behavior- "r

The vast majority of the human genome consists of noncoding elements, including introns, intergenic regions, and various types of noncoding RNAs (ncRNAs). As such, protein-coding genes represent only 1.5% of the transcriptome while the remaining 98,5% are ncRNAs. Long non-coding RNAs (lncRNAs) form the largest class of ncRNAs and are characterized by a length of more than 200 nucleotides. The role of lncRNAs in the central nervous system (CNS) is still not well understood. In this project we identified a novel lncRNA that we named CNS-LNC due to its specific expression pattern in the adult bra

…modifier with largely unknown neuronal functions. In humans, heterozygous loss of function mutations in CHD2 are associated with severe childhood-onset epilepsy, global developmental delay, intellectual disability, and autistic-like features. Here, we characterized the epileptic and behavioral phenotypes of a mouse model with Chd2 haploinsufficiency (Chd2+/m and Chd2m/m mice). Interestingly, we discovered th

Diurnal animals with monophasic sleep patterns exhibit species-specific cycles of slow-wave sleep (SWS) alternating with rapid eye movement sleep (REMS). A recent study revealed that in the diurnal reptile Pogona vitticeps, SWS and REMS regularly alternate with approximately 2-min cycles throughout the night, generating more than 300 SWS/REMS cycles. Although the cycle varies significantly across species, common neural mechanisms may be involved. However, the precise mechanisms responsible for maintaining these regular cycles remain elusive. Sleep-wake patterns are predominantly regulated by t

…How neuronal activity encodes visual features in the primary visual cortex (V1) in lit environments and under various luminance levels has been well-studied in many mammalian species. However, how the functionally distinct superficial and deep cortical layers of the V1 encode abrupt and sustained changes in light conditions in freely exploring animals remains unclear. To address this question, we recorded neuro

The endocannabinoid system (ECS) has gained attention as a potential target to treat Alzheimer’s disease (AD) due to its neuroprotective, antioxidant, and anti-inflammatory properties. Consequently, natural cannabinoids like delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have emerged as potential drugs against AD. Previous findings from our research group demonstrated that a combination of non-psychoactive doses of THC and CBD mitigates cognitive decline in an AD murine model, the APP/PS1 mice. Cognitive decline in AD is linked to the dysregulation of glutamate transmission within the

…were necessary for recording neuronal action potentials, potentially increasing brain tissue damage[4

Androgen Receptor (AR) is a steroid hormone-activated transcription factor located in the cytoplasm in an inactive state. In response to androgen binding, AR shuttles from the cytosol to the nucleus, where it regulates the expression of specific AR target genes. AR is widely expressed throughout the brain, hippocampus, hypothalamic nuclei (like the preoptic area, POA), and amygdala. AR gene is located in the X chromosome; therefore, it is present in a single copy in men. Males lacking or expressing mutant AR display female-like external sexual organs and infertility, which are recapitulated in

…acetylcholine (ACh), and intrinsic neuronal firing, bearing profound implications for disorders like Parkinson's. However, the interaction between striatal DA and ACh, and their collective impact on striatal neuron activity in health and disease, are not fully understood. This study aims to elucidate the complex interplay between ACh, DA, and neuronal activity in the striatum during sensory and motor events. Utilizing a specialized Delayed-Go reaching task for head-fixed mice, we re

Learning by experience that certain cues in the environment predict danger is crucial for survival. How dopamine (DA) circuits drive this form of associative learning is not fully understood. Here, we demonstrate that DA neurons projecting to a unique subregion of the dorsal striatum, the posterior tail of the striatum (TS), encode an aversive prediction error (PE) signal during associative fear learning. These DA neurons are necessary specifically during acquisition of fear learning, but not once the fear memory is formed, and are not required for forming cue-reward associations. Notably, tem

…is an adaptive process that depends on neuronal activity. We recently demonstrated that neuronal activity in vivo enhances remyelination in demyelinated lesions (Ortiz et al., 2019, JCI Insight). Here, we investigate whether calcium singal in oligodendroglia play a role in remyelination and whether beha

…of the task, individual and concerted neuronal activity is related to behaviour, task episodes, and prediction of future choices. However, not every choice arises from the same motivation. Choices can be spontaneous, based on information from previous experience, or querying for additional information. What are the neuronal dynamics governing these possibilities? We simultaneously record hundreds of individual neurons from the mouse prefrontal cortex using silicon probes. Head-fixed animals engage in a probabilistic 2-si

…avenue for recording and perturbing neuronal activity. This technology holds potential for gaining better insights into cortical networks due to these characteristics. To comprehend local networks of the motor cortex and monitoring network changes during stimulation, we utilized subdurally positioned graphene electrodes for simultaneous recording and stimulation of the motor cortex in rhesus monkeys. Additionally, we implemented a wireless recordin

The modern world is increasingly dependent upon artificial intelligence and machine learning. Applications range from decision-making in areas such as health and finance to autonomous vehicle control. However, current deep-learning machines and neural network algorithms have important limitations, namely ineffective learning rules, long training, and high power consumption (1). In the present project, we aim to address these limitations by using the human nervous system itself as a model, which can process external information in a power-efficient way. To accomplish this objective, we utilize

…We captured neuronal activity using whole-brain immunolabeling for the immediate early gene cFos, iDISCO tissue clearing (Renier et al., 2014), and light-sheet fluorescence micro

…deals with detailed imaging of neuronal structures, functional monitoring of red blood cell velocity and calcium dynamics located in the deepest regions of anaesthetized mice [4]. In addition to technological development, the transition to imagi

Functional ultrasound imaging (fUSI) can record neuronal activity down to 20 mm depth in the brain, at finer resolution than functional magnetic resonance imaging. We developed an acquisition add-on, analysis and visualization pipeline that allows efficient identification of anatomical and functional layout of the brain in 3D. Leveraging the high signal quality of fUSI, we asked whether the acquisition of multi-cm 3D functional maps can be made compatible with chronic anesthetized experiment design. Since availability of large-brained species is low and their behavioral training can be prohibi