Granule cells

…Granule cells (GCs) of the DG receive their major spatial cortical input from the medial entorhinal cortex (MEC) via the perforant path. To determine whether inputs from the MEC (in particular layer II stellate cells) play a role in the capacity of the DG to differentiate between different environments, we aim to modulate their activity using DREADDs. Thanks to these pharmacogenetic tools, we can de- or hyper-polarize MEC-layer II stellate cells during e

…and spine remodelling of dentate gyrus granule cells after denervation. Our research aims to investigate the effect of the layer-selective denervation of the dentate gyrus on the proliferation and differentiation of neurons in the granule cell layer, as the mechanisms that drive the remodelling due to the loss of input are not yet understood. Therefore, in anaesthetised adult male C57Bl/6 mice, the transection of the perforant pathway was performed, resulting in the layer-specific denervation of dentate granule

Schinzel-Giedion syndrome (SGS), a rare developmental disorder characterized by congenital anomalies, intellectual impairment and epilepsy, is attributed to de novo point mutations affecting SET binding protein 1 (SETBP1). These mutations lead to pathological protein accumulation, triggering a cascade of downstream effects, partially understood. Considering the significant neurological consequences of such germline mutations, it is reasonable to speculate that SETBP1 plays a crucial role during central nervous system development, although limited data are available. To dissect SGS epileptogene

The dentate gyrus (DG) serves as an information gateway to the hippocampal formation. It receives sensory information from entorhinal cortex via perforant path (PP) and can be subdivided into parts including a supra- and an infrapyramidal blade. Typically, synaptic plasticity within the DG has mostly been examined in the suprapyramidal blade, whereas little is known about the extent to which synaptic plasticity is expressed and maintained in the infrapyramidal blade.This study compared synaptic plasticity in both blades of the DG that was evoked by patterned electrophysiological stimulation of

…dDG granule cells interact with various interneuron subtypes, forming a complex local circuit essential for stress processing. Studies have shown differential activity in specific interneuron subtypes in response to stress, impacting coping mechanisms.This study examines the impact of two distinct categories of DG interneurons, chandelier and basket cells, on coping behavior. Ephrin A7 (EphA7) stabilizes synaptic terminals in basket cells, while Neurofascin (NF) facilitates axo-axonic synapse formation

…pathways of the EC connecting to granule cells (GC) of the DG play a role in memory encoding and information processing. LPP- and MPP-GC synapses have distinct electrophysiological properties, and these differences potentially affecting the functional processing of information. However, the plasticity of these synapses i

In the dentate gyrus (DG), granule cells (GCs) and local interneurons transform dense cortical neuron ensemble theta/gamma band activity into sparse DG output to generate contextual representations. GABAB receptor-mediated inhibition contributes to sparse DG activity, but it is unclear how it contributes to frequency-dependent synaptic integration and spike output. We recorded perforant-path excitatory postsynaptic potentials from GCs in ventral horizontal slices from adult male and female mice and found GABAB-receptor dependent inhibition of action potential firing during gamma frequency trai

…of new environments, groups of DG granule cells (GCs) become active and form new memories. The activity of GCs is strongly modulated by a large network of inhibitory interneurons (INs) that allow the sparsification and orthogonalization of cortical inputs. Recently, a novel population of GABAergic INs expressing the Neuron-Derived Neutrophic Factor (NDNFIs) has been identified as a key component in the modula

…is conveyed by mossy fibers to granule cells (GC) contacting Purkinje cells (PC) belonging to different modules via their long axons, the parallel fibers (PFs). PFs underlie inter-modular communication, which may be at the core of motor coordination. Therefore, the main goal of our research is to understand how intermodular communication in the cerebellar cortex underlies motor adaptation.Using patterned light photostimulat

DYT1 is an autosomal dominant form of dystonia, linked to a deletion (ΔGAG) in the TOR1A gene. The basal ganglia have been found to play a crucial role in the development of dystonia in the TOR1AΔGAG murine model. Experimental evidence has also indicated that the cerebellar cortex is likely to play a pivotal role in the pathophysiology of this disorder. We investigated cerebellar cortex activity and synaptic plasticity by performing extracellular recordings in acute parasagittal cerebellar slices with a high-density multielectrode array (HD-MEA) that allows to simultaneously record the activit

…mossy fibres (MF), onto CA3 pyramidal cells in the hippocampus. Neurotransmitter release occurs through two primary modes: action potential induced release and spontaneous fusion of synaptic vesicles. These modes are underpinned by distinct pools of vesicles, exhi

…sensorimotor input to a dense layer of granule cells (GrCs). GrCs relay this information through parallel fibre (PF) projections that synapse with Purkinje cells (PCs), the sole output of the cerebellar cortex, and molecular layer interneurons (MLI), which provide feedforward inhibition of PCs. Accordingly, PCs compute incoming sensorimotor patterns and send inhibitory outputs that rapidly adjust motor movemen

Vasopressin (VP) cells in the rat olfactory bulb (OB) have unique features compared to other types of external tufted cells, with olfactory nerve input inhibiting them and added cholinergic neuromodulation enabling them to fire. However, how VP modulates bulbar synaptic transmission to facilitate social discrimination is still unclear. As first step, we recorded responses to olfactory nerve stimulation and their modulation by VP (1 µM) using electrophysiology as well as 2-photon population Ca2+ imaging in acute OB slices. We first investigated the excitatory middle tufted and mitral cells. In

A fundamental goal of neuroscience is the functional understanding of neural circuit architecture. Previous studies revealed the importance of network depth in visual and auditory circuits, but it remains elusive why predominantly non-convolutional circuits, such as the cerebellum or olfactory systems, have multiple feedforwardly connected layers. Recent deep learning works revealed that a two-hidden-layer network has a quadratically more memory capacity than a single-hidden-layer network with the same number of hidden layer neurons, suggesting the importance of the network depth for memory ca

…fibre input typically projects to 250 granule cells, a population that comprises more than half of the neurons in the brain. Each granule cell forms ~4 synapses with mossy fibres. The main hypotheses for this sparse input expansion are that it facilitates pattern separation1 and smoo

Neural circuits must perform probabilistic computations to efficiently process noisy sensory information. Sampling codes propose that single neuron variability is a signature of probabilistic computation, and corresponds to sampling the space of possible solutions in proportion to their posterior probability. Under this hypothesis, the neural code defines how variables inferred by the network are represented in single neurons. Compared to other proposed probabilistic codes, the capacity of sampling codes scales with the number of neurons, but their convergence speed scales poorly with dimensio

…their input into a vast layer of granule-like cells. Signals are typically routed to such expanded representations by anatomical “bottlenecks”: in the mammalian cortico-cerebellar pathway, input from across the cortex converges in the pontine nuclei, from which roughly half of the mossy fiber input to gra

The Hsieh lab focuses on the mechanisms that promote neural stem cell self-renewal and differentiation in embryonic and adult brain. Using mouse models, video-EEG monitoring, viral techniques, and imaging/electrophysiological approaches, we elucidated many of the key transcriptional/epigenetic regulators of adult neurogenesis and showed aberrant new neuron integration in adult rodent hippocampus contribute to circuit disruption and seizure development. Building on this work, I will present our recent studies describing how GABA-mediated Ca2+ activity regulates the production of aberrant adult-

…from the input mossy fibres to the granule cell layer. For years, theories of how cerebellar architectural features relate to cerebellar function have been formulated. It has been shown that some of these features can facilitate pattern separation. However, these theories don’t consider the need for it to learn fast in order to control smooth and accurate movements. Here, we confront this gap. This talk w

…the expansion in neuron number of the granule cell layer and their synaptic in-degree, and sparse coding by granule cells. Typically, these theories focus on the learning of random

The role of granule cells in olfactory processing is surrounded by several enigmatic observations, such as the existence of reciprocal spines and the mechanisms for GABA release from them, the missing evidence for functional reciprocal connectivity, and the apparently low inhibitory drive of granule cells, both with respect to recurrent and lateral inhibition. Here, I summarize recent results with regard to GABA release, leading to a novel hypothesis on granule cell function that has the potential to resolve most of these enigmas. I predict that granule cells provide dynamically switched later