Interneurons

Interneurons, ubiquitous in the central nervous system, form networks connected through both inhibitory chemical synapses and gap junctions. These networks are essential for regulating neuronal activity notably by regulating temporally patterned dynamic states. We aim to understand the mechanisms that allow for synchronization to arise in networks of interneurons with both chemical synapses and electrical gap junctions (Panel 1). To this end, we use the exact mean-field reduction, often referred to as the “neural mass model” in the literature (Montbrio et al, PRX, 2015). We first analyse a sin

Epilepsy provides a unique opportunity to study human cellular electrophysiology through in vivo and in vitro approaches. In vivo recordings offer advantages in action potential pattern reconstruction and connection preservation, while in vitro studies allow broader tissue exploration within a confined space of cut connections, yet coherent investigation in these distinct conditions is lacking. This study compared single-neuron firing properties in four epileptic patients using identical 24-channel laminar microelectrodes with 150 μm inter-contact distance for both their in vivo and in vitro i

…and inhibitory), astrocytes, or interneurons in CB1-flox males and females was performed. Viral vectors (AAV-Cre) were injected bilaterally into the hippocampus of these mice. The Barnes maze was used for learning, memory, navigation and the Novel Object Recognition Test (NORT) for recognition memory. Anxiety-like behavioural protocols were also performed b

Mechanosensory neurons across the body have axon projections that terminate in distinct arborizations in the brain corresponding to body location. These somatotopically-organized projections provide the interface with neural circuits that direct body location-appropriate behavioral responses, such as aimed grooming. Using electron microscopy-based reconstructions, we investigate how circuits transform mechanical stimulations into location-appropriate behavior. We previously described the somatotopic organization of bristle mechanosensory neurons (BMNs) around the Drosophila head that elicit a

We often perceive memories as unified experiences although they comprise a multiplicity of different modalities and features. How the different aspects of a memory are encoded separately or jointly in the brain’s memory systems is not well understood. A key brain structure that has been identified to be involved in processing emotional memories is the ventral hippocampus. In our study we use virtual environments to induce in head-fixed mice the recall of distinct memories of a trace fear conditioning, consisting of a cue-triggered temporal and a context-triggered emotional component. To invest

…in a single organism how motor and interneurons in the spinal cord generate these behaviors. Here, utilizing advances in genetic manipulation and behavioral tracking, we dissect the molecular features and contribution of each spinal cord cardinal class to swim versus limb behavior over frog metamorphosis.We devise a high-throughput CRISPR screen, in which we knock ou

…glutamatergic synapses arriving onto interneurons and disynaptic GABAergic synapses using dual whole-cell patch clamp r

Replay of neuronal activity patterns during sharp-wave ripples (SPWr) is a crucial event for memory consolidation. Past events reactivation can be estimated by the explained variance (EV) between the pairwise neuronal correlations of consecutive behavioral episodes.We have investigated the physiological mechanisms of hippocampal reactivation in mice after the exploration of a linear maze. We found a strong reactivation during the subsequent SPWr events (EV=33.2±17.15%; n=19sessions), which did not correlate with changes in the average firing rate or the ripple rate of pyramidal neurons or inte

Mechanosensory neurons located on the body surface show somatotopic organization in their projections into the central nervous system and elicit diverse behavioral responses, from relatively simple stimulus location-aimed movements to complex movement sequences. How mechanosensory neurons and their postsynaptic circuits influence such diverse behaviors remains unclear. We previously identified nearly all mechanosensory neurons around the Drosophila head whose individual stimulation elicit aimed grooming of specific head parts (e.g. eyes or mouthparts) while their simultaneous stimulation elici

…(68%) and putative inhibitory interneurons (24%), within a sample of 147 single units recorded from the dorsolateral PFC of two macaque monkeys while they performed a Transitive Inference (TI) task. The TI task required learning the relationship between the adjacent items of an arbitrarily rank-ordered sequence in every session, i.e., A>B>C>D&g

…cells) and inhibitory neurons (interneurons), which is disrupted in disorders such as autism or schizophrenia. The emergence of cortical function during postnatal development relies on spontaneous synchronous activity among large groups of pyramidal cells and interneurons, which later desynchronise for efficient information processing. Before this network activity shift, interneuron numbers are adjusted through activity-dependent programmed cell death mechanisms. However, the extent to which the ad

…(MSNs) and the local neurons or interneurons. While recent studies in the mouse striatum employing advanced technologies have unveiled a significantly broader spectrum of neuronal subtypes, it remains unclear how this diversity extends to the human brain. Here, we conducted single nuclei RNA-seq (snRNA-seq)

The extracellular matrix glycoprotein reelin is best known for orchestrating migration and positioning of cortical neurons during embryonic development. The reeler mutant mouse, lacking reelin expression, displays severe migration defects and aberrant dendritic development of cortical neurons. Less is known about the consequences of postnatally induced reelin deficiency in conditional reelin knockout (reln cko) mice. Postnatally induced reln cko was shown to entail functional deficits of neuronal communication, while morphological deficits of neurons have not been reported so far. Here, we inv

…Interneurons in the adult mouse cortex are diverse, they can be defined based on developmental origin, distinct morphology, physiological and molecular properties (e.g. parvalbumin-expressing basket cells). Despite making up approximately 1/6 of the total neuronal population we do not currently have a cortex-wide map of interneurons.Using transgenic mice to label cells we have mapped the distribution of all interneurons, of 2 broad populations (MG

The precise generation of diverse neuronal cell types is crucial for normal brain function. Genetic mutations leading to impaired neuronal development have long been linked to neurodevelopmental disorders. Cerebral organoids can be used to investigate neurodevelopmental disorders in a human context but are limited by variability and low throughput. We have developed the CRISPR-human organoids-scRNA-seq (CHOOSE) system that utilizes verified pairs of gRNAs, inducible CRISPR/Cas9-based genetic disruption, and single-cell transcriptomics for pooled loss-of-function screening in mosaic organoids.

Parvalbumin-positive GABAergic interneurons (PV-INs) provide inhibitory control of excitatory neuron activity, coordinate circuit function, and regulate behavior and cognition. PV-INs are uniquely susceptible to loss and dysfunction in traumatic brain injury (TBI) and epilepsy but the cause of this susceptibility is unknown. One hypothesis is that PV-INs use specialized metabolic systems to support their high-frequency action potential firing and that metabolic stress disrupts these systems, leading to their dysfunction and loss. Metabolism-based therapies can restore PV-IN function after inju

To form a coherent perception of the world around us, we are constantly processing and integrating sensory information from multiple modalities. In fact, when auditory and visual stimuli occur within ~100 ms of each other, individuals tend to perceive the stimuli as a single event, even though they occurred separately. In recent years, our lab, and others, have developed rat models of audiovisual temporal perception using behavioural tasks such as temporal order judgments (TOJs) and synchrony judgments (SJs). While these rodent models demonstrate metrics that are consistent with humans (e.g.,

Biological neural networks use an abundance of “recurrent” connections, yet state-of-the-art deep neural network based computer vision models are predominantly feedforward. Why does biological vision evolve to employ recurrence pervasively? In this paper, we aim to address this question from a machine learning and modeling framework highlighting a critical functional advantage of employing recurrent computations: we show that a recurrent network is naturally able to adapt its computational budget flexibly during inference and generalizes in a zero-shot manner within-task across difficulties. W

Advances in functional brain imaging now allow sustained rapid 3D visualization of large numbers of neurons inside behaving animals. To decode circuit activity, imaged neurons must be individually segmented and tracked. This is particularly challenging when the brain itself moves and deforms inside a flexible body. The field has lacked general methods for solving this problem effectively. To address this need, we developed a method based on a convolutional neural network (CNN) with specific enhancements which we apply to freely moving C. elegans. For a traditional CNN to track neurons across i

…(photoreceptors, three groups of interneurons, and retinal ganglion cells) can be divided into 130 discrete types. We then applied the method to other species including human, macaque, zebrafish and chick. With the atlases in hand, we are now using them to address questions about how retin

…and rats suggest the existence of interneurons in the lumbar spinal cord that mediates that step: the spinal ejaculation generator (SEG). My work aimed at gaining mechanistic insights about the neuronal circuits controlling ejaculation thereby applying cutting-edge techniques. More specifically, we mapped anatomically a

…between pyramidal cells and putative interneurons. Using arbitrary white noise patterns injected intra-cortically as photocurrents to freely-moving mice, we find that directly-activated cells exhibit precisi

Each spring, billions of Bogong moths escape hot conditions in different regions of southeast Australia by migrating over 1000 km to a limited number of cool caves in the Australian Alps, historically used for aestivating over the summer. At the beginning of autumn the same individuals make a return migration to their breeding grounds to reproduce and die. To steer migration Bogong moths sense the Earth’s magnetic field and correlate its directional information with visual cues. In this presentation, we will show that a critically important visual cue is the distribution of starlight within th

Basket cells are key GABAergic inhibitory interneurons that target the somata and proximal dendrites, enabling efficient control of the timing and rate of spiking of their postsynaptic targets. In all cortical circuits, there are two major types of basket cell that exhibit striking developmental, molecular, anatomical, and physiological differences. In this talk, I will discuss recent results that reveal the tightly coupled complementarity of these two key microcircuit regulatory modules, demonstrating a novel form of brain-state-specific segregation of inhibition during spontaneous behavior,