Electrophysiological recordings

The ability to learn and adapt to cognitive demands is vital for survival, and mice serve as valuable models in neuroscience for studying these processes. In this study, we introduce a novel maze framework to investigate learning and adaptability in mice, specifically focusing on humanized App knock-in models of Alzheimer's disease. The maze mimics decision-making scenarios, similar to when foraging, with an optimal reward path leading to a target with sucrose pellets. Decision nodes introduce off-reward routes to dead-ends or loops, creating a challenge requiring mice to balance exploration w

The sleeping brain is in a constant tradeoff between maintaining its quiescent state, thought to support homeostatic processes, and interrupting it to deal with external contingencies such as threat. While evidence suggests that sleep interruption is an associative contextual process, little is known about its underlying neural substrates. Here, inspired by evidence that sleep interruption in humans relies on associative and contextual components, we develop a paradigm in mice to identify its circuit mechanisms. By training mice on an active avoidance task variant, we discover that auditory co

Electrophysiological recordings capture signals from hundreds of neurons simultaneously, but isolating single-cell activity often requires manual curation due to limitations in spike- sorting algorithms. As dataset sizes grow, the time and expertise required for accurate and consistent human curation pose a major challenge for experimental labs. To address this issue, we developed UnitRefine, a classification toolbox that leverages diverse machine-learning algorithms to minimize manual curation efforts. Using acute recordings with Neuropixel probes, we collected a large neural dataset with hig

Current electrophysiological approaches can track the activity of many neurons, yet it is usually unknown which cell-types or brain areas are being recorded without further molecular or histological analysis. Developing accurate and scalable algorithms for identifying the cell-type and brain region of recorded neurons is thus crucial for improving our understanding of neural computation. In this work, we develop a multimodal contrastive learning approach for neural data that can be fine-tuned for different downstream tasks, including inference of cell-type and brain location. We utilize this a

Despite the large number of active neurons in the cortex, the activity of neuronal populations is expected to lie on a low-dimensional manifold for different brain regions [1]. Variants of principal component analysis (PCA) are commonly used to assess this manifold. However, these methods are limited by the assumption that the data follows a Gaussian distribution and neglect additional features such as the curvature of the manifold. Hence, their performance as generative models tends to be subpar. To construct a generative model that entirely learns the statistics of neural activity with no a

Information in sensory neurons is conveyed by spiking activity varying in time. This is quantified by the mutual-information rate (MIR), given by $\mathrm{MIR}:=\underset{\Delta t\rightarrow\infty}{\lim}\frac{{\cal I}\left(\Delta t\right)}{\Delta t}$, where ${\cal I}\left(\Delta t\right)$ is the mutual information between the activity of a spiking neuron and a stimulus over a given time window $\Delta t$. To compute it for spiking data, the spike train is typically discretized with a certain bin-size $\mathrm{dt}$. Because $\Delta t/\mathrm{dt}$ is typically well bigger than $1$, there are man

The prefrontal cortex (PFC) is known to be involved in working memory, executive control, attention, and decision making. It integrates internal information and states with external information from the environment which results in timely and appropriate behavioral responses. It remains unknown how distinct excitatory cell types within PFC contribute to population activity and behavior. We investigate two major excitatory cell types within the PFC - extratelencephalic (ET) and intratelencephalic (IT) neurons. Anatomical analysis in transgenic mouse lines shows that ET neurons project to subcor

After excitotoxic lesions, subsets of striatal astrocytes undergo spontaneous neurogenic activation, leading to the local generation of a large number of neuroblasts for at least six months post-lesion. However, the functional integration of the lesion-induced neurons remains unclear. Fate mapping and 3D reconstruction analyses reveal that striatal neuroblasts undergo a maturation process in which they initially organize in clusters, subsequently disperse as individual cells, and gradually attain complex morphologies, often exhibiting dendritic spines. These neurons fail to express typical mar

…tasks have been developed for electrophysiological or imaging studies in head-fixed mice, there remains a scarcity of tasks incorporating neurophysiological recordings within a more ecologically realistic setting involving freely moving animals. This study introduces a tactile discrimination task for freely moving mice, integrating electrophysiology and calcium imaging with cellular resolution. In this go/no-go paradigm, mice learn to discrimin

Epileptiform activity (EA) comprises abnormal excessive neuronal discharges (spikes and sharp waves) detectable by electroencephalogram. The term EA originates from epilepsy research, where interictal EA appears in EEG between seizures. Importantly, EA occurs not only in epilepsy but also in various pathologies, possibly contributing to cognitive impairment. EA has been observed in neurodegenerative disorders like Alzheimer's and Parkinson's diseases. However, a direct causal link between EA and cognitive impairment remains elusive. A significant issue is the lack of a pure EA model for invest

Projections from basal forebrain cholinergic neurons (BFCNs) densely innervate neocortex, releasing acetylcholine to regulate arousal, sensory processing and learning. Although the cholinergic system is one of the extensively studied neuromodulatory system, its impact on cortical processing remains unclear. Earlier studies have shown that BFCNs in rostral and caudal basal forebrain nuclei respond largely similar to reward and punishment despite their non-overlapping cortical projections, suggesting that BFCNs act as a unified broadcasting system. In contrast, more recent findings revealed dist

The prefrontal cortex is a core limbic region crucial for emotional memory formation and adaptive decision-making. Accumulating evidence across species highlights the distinct roles of prefrontal subregions in various behaviors and memory processes. Despite this understanding, little is known about how distinct features of associative memories are encoded in neuronal ensembles within and across distinct prefrontal subregions and the role of these representations in the encoding and retrieval of emotional memories. In this study, we aim to elucidate the interplay between prefrontal subregions a

Memories are thought to be stored as material changes occurring in sparse, widely distributed populations of neurons known as engrams. This neural plasticity is theorised to promote re-activation of this network of engram cells upon re-exposure to relevant cues, thus leading to memory retrieval. Significant evidence exists to support this theory in relation to highly aversive or rewarding experiences, however less evidence exists to support the existence of engrams for day-to-day learning experiences. Here we used TRAP2 mice to characterize expression patterns and plasticity in neurons activat

Breathing, a quintessential physiological process, has garnered increasing attention for its profound impact on brain function. Recent investigations have established the pivotal role of respiration in orchestrating rhythmic neuronal activity, facilitated by two primary pathways: efferent intracerebral projections from rhythm generators and reafferent inputs via the olfactory pathway. This intricate interplay between respiration and limbic neuronal dynamics has spurred hypotheses regarding the potential role of breathing in supporting the synchronization of limbic circuits.Yet, elucidating the

The first-line pharmacological treatments for PTSD patients are serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs). However, both treatments achieve full recovery in fewer than 30% of patients, underscoring the variability in responsiveness among individuals. To this day, there is a profound lack of knowledge regarding the neural mechanisms underlying responsiveness to these treatments. In our study, employing a male rat model of PTSD, we utilized individual behavioral profiling (IBP) following comprehensive behavioral assessments to distinguish between trauma-affected

…capabilities constrain brain organoid electrophysiological research. Classical microelectrode arrays (MEA) fall short in capturing data from intact organoids, which may flatten in the 2D-MEA surface, jeopardizing physiological responses and data validity. To overcome this, we pioneered a mesh MEA, preventing morphological deformations, fostering 3D growth, and facilitating electrical activity recording within intact organoids over an extended period. Electrophys

Neuromodulators have a key role in mediating cognitive processes such as attention, learning and memory. Disorders of the neuromodulatory systems underlie certain degenerative neurological conditions like Alzheimer’s and Parkinson’s diseases. While the role of neuromodulators in explicit learning is increasingly in the focus of the research, their participation in implicit learning and memory processes is poorly understood.To examine this we have used a previously developed automated training setup in which animals must respond to sequential light flashes at different locations. Following the

Rett syndrome (RTT) is a devastating neurodevelopmental disorder primarily affecting females, characterised by the loss of motor skills and behavioural abnormalities linked to an excitatory/inhibitory imbalance involving GABA dysfunction. GABAergic deficits, particularly in somatostatin (SST) interneurons, play a crucial role in RTT pathophysiology and have been successfully replicated in mouse models. This study delves deeper into understanding the role of GABAergic interneuron inhibition in an RTT mouse model. Neonatal injections were administered to Mecp2tm1.1Bird x Sst-IRES-Cre mice at P1,

Intellectual Disability-Autism spectrum disorder (ID-ASD) are complex neurodevelopmental diseases characterized by a wide spectrum of deficits in cognitive, social and adaptive functions. Among the X-linked gene associate to ASD-ID, OPHN1 encodes a Rho GTPase-activating protein (Rho-GAP) expressed in neurons and non-neuronal cells, during development and in adulthood, in brain areas with a high degree of plasticity, such as the cortex, the hippocampus, and the olfactory bulb (OB). Several evidence indicate that part of the ID-ASD pathology can be ascribed to defects in synaptic morphology and

During Gaze stabilization extraocular muscles produce reflexive compensatory eye movements to fix the image on the retina. Among such a complex sensorimotor transformation the vestibulo-ocular reflexes (VOR), generating compensatory eye movements in response to head motion, require vestibular inputs which are integrated by extraocular motoneurons.In Xenopus larvae, the onset of the angular VOR (aVOR) is delayed compare to other visuo-vestibular reflexes. This delay could imply the existence of distinct parallel pathways in vestibulo-ocular networks, involving distinct motoneuron functional sub

Lithium is a primary treatment for patients with bipolar disorder, effectively managing the extreme mood swings. However, side effects of lithium treatment including increased thirst often lead to significant discomfort and potentially impact patient compliance with the medication regimen. In an effort to understand the underlying mechanisms of lithium-induced thirst, we have conducted studies using mice as a model organism. These studies involve administering lithium chloride (LiCl) either through intraperitoneal injections or by supplementing lithium salts into the animals' diet. Observation

The corticolimbic network plays a significant role in regulating emotional behavior. Stress-induced dysfunctions in this network are associated with mental illnesses, including major depressive disorder (MDD). Despite being one of the most prevalent mental disorders, the pathogenic mechanisms of MDD remain unclear. Serotonin has been associated with MDD as a promising factor for over 60 years. However, serotonergic dynamics have only recently been linked to corticolimbic network activity. We aim to investigate the effect of serotonin on corticolimbic network activity, specifically in the media

…arrays (HD-MEAs) enable non-invasive electrophysiological recordings from various electrogenic samples, including iPSC-derived neurons, retinal explants, brain slices, and neural organoids.In this study, we

Recent studies showed that flexible, ultra-thin, polyimide electrodes implanted in mouse V1 elicit chronically stable intracortical microstimulation (ICM) with low activation threshold and high biocompatibility, demonstrating their promising use as prosthetics for visual restoration. However, these works did not explore the full repertoire of parameters that can shape the ICM. Besides, to achieve precise spatial encoding of the visual field, it is necessary to identify the stimulation conditions that lead to localized neuronal activation around the stimulation site(s). We have developed a pipe