Axon initial segment

This meeting examines how the axon initial segment controls neuronal firing and polarized transport. The programme connects axo-axonic synapses and human neuronal physiology with cytoskeletal organization, development, disease and activity-dependent plasticity. Approaches include electrophysiology, proteomics, nanoscale and ultrafast imaging, computational modelling and CRISPR perturbation. Discussions consider how ion channels, molecular scaffolds and synaptic inputs jointly regulate excitability. Sessions begin at 09:00 on 7 December and 09:30 on 8 December 2026, in GMT (Europe/London, UTC+

The neocortex is built up from homologous neuron types, but neurons exhibit between-species differences in gene expression, molecular profile, and electrical function. Purpose of these specializations is not well understood. In human neocortex, fast-spiking interneurons have high electrical excitability compared to their rodent counterparts. This slows down time course for cell membrane potential changes, and in theory, makes human fast-spiking neurons slower than rodent cells to process electrical input signals and generate action potential (AP). However, human neurons are nearly as fast with

…interneuron subtype that forms axo-axonic synapses at the axon-initial segment (AIS) of pyramidal neurons, are optimally positioned to regulate network-wide spiking activity. It has been shown that chandelier cells change the number and density of their axon-targeting synapses onto L2/3 pyramidal neurons following chronic changes in net

The axon initial segment (AIS) is a critical compartment in neurons. It converts postsynaptic input into action potentials that trigger information transfer to target cells. This process relies on several voltage-gated sodium (Nav) and potassium (Kv) channels that accumulate in high densities at the AIS. Here, we identify the mechanosensitive potassium channel TRAAK (K2P4.1) as a component of the AIS in adult rat hippocampus and in cultured rat hippocampal neurons. We furthermore show that the AIS localization of TRAAK is driven by a C-terminal sequence that bears resemblance to ankyrin G bind

…and forms complexes in synapses and axons via the receptors ADAM22/23 with Kv1 potassium channels and structural proteins such as PSD95 and glutamate receptors, whereby LGI1 can exert an influence on synaptic transmission and intrinsic excitability. To understand changes in neuronal function by LGI1 encephalitis, we used patients’ serum IgGs or monoclonal a

Recent studies have shown that ON-alpha sustained (ON-αs) retinal ganglion cells (RGCs) exhibit distinct distribution patterns within the mouse retina, with a notable prevalence observed in the temporal region. RGCs rely mainly on presynaptic inputs to create meaningful outputs, however the contribution of postsynaptic RGC processing is unknown. Therefore, we compared the intrinsic spiking properties of nasal and temporal RGCs in the wild-type and degenerated mouse retina. Whole-cell patch clamp experiments were performed to measure the responses of temporal and nasal ON-αs RGCs in wild-type a

The UBE3A gene codes for an E3 ubiquitin ligase and is critical to ensure a proper brain function. Indeed, perturbations of UBE3A dosage or function result in pathological phenotypes. Loss of UBE3A causes the Angelman Syndrome, a severe neurodevelopmental disorder characterized by intellectual disability, motor delay and seizures, while increased UBE3A copy number or activity are strongly associated with Autism. Importantly, the molecular underpinnings of UBE3A-associated pathogenic mechanisms of neurodevelopmental disorders are still poorly understood. In this project, we study the effects of

…(PNs) such as dendrites, soma and axon initial segment (AIS) thus shaping the cellular computations underlying memory formation. Yet, very little is known about the long-term structural dynamics of these compartmentalized inhibitory synapses on PNs and their link to learning.To address these outstanding questions, we used longitudinal in viv

The axon initial segment (AIS) is an axonal subdomain integral to neuronal excitability, yet its geometrical diversity within the hippocampus is poorly understood. This study provides a detailed examination of the variability of proximal cell morphology across murine hippocampal neurons, analyzing molecular and geometrical parameters such as AIS length and position, dendrite shape, soma, and apical dendrite size across dorsal-ventral, superficial-deep, and proximal-distal axes. We observed significant differences in AIS characteristics, with CA3 neurons displaying longer AIS and more distal or

…properties of RGCs such as the axon initial segment (AIS) also play an important part in signal modulation.Whole-cell patch-clamp experiments were performed to measure the spiking responses of ON-alpha sustained (ON-αs), OFF-alpha sustained (OFF-αs), and OFF-alpha transient (OFF-αt)

…of the action potential (AP) at the axon initial segment (AIS). Chandelier cells (ChCs), a GABAergic interneuron subtype, targets the AIS of pyramidal neurons through axo-axonic synapses and is therefore thought to strongly modulate neuronal output. We used super-resolution microscopy (S

…MPS is particularly pronounced in the axon, where it appears able to recruit ion channels and signaling platforms into similar periodic localization patterns, suggesting the MPS plays a key role in orchestrating neuronal signaling. Despite this, precise quantificati

…the rodent CNS, specifically along the axon initial segment (AIS), a critical neuronal microdomain responsible for the initiation of action potentials. However, details about the subce

…pyramidal cells through axo-axonic synapses which target the axon initial segment (AIS). Despite their importance in modulating circuit activity, our knowledge of the development and function of axo-axonic synapses remains elusive. We have investigated the emergence and plasticity of axo-axonic synapses in layer 2/3 of the somatosensory cortex (S1) and found that ChCs follow w

Can alterations in experience trigger different plastic modifications in neuronal structure and function, and if so, how do they integrate at the cellular level? To address this question, we interrogated circuitry in the mouse olfactory bulb responsible for the earliest steps in odor processing. We induced experience-dependent plasticity in mice of either sex by blocking one nostril for one day, a minimally invasive manipulation that leaves the sensory organ undamaged and is akin to the natural transient blockage suffered during common mild rhinal infections. We found that such brief sensory d