Neuronal excitability

…and technical detection limits to neuronal excitability, clinical heterogeneity and treatment resistance. Thematic presentations and an interactive panel address multi-omics study design, clinical phenotyping, biomarkers and therapeutic development, connecting molecular mechanisms to precision medicine and surgical decisions. Sunday 6 December, 08:30

…conditions, where otherwise normal neuronal activity can generate occasional seizures. It is thus important to better understand the pathological changes that may be

…criticality, we analyze a model of neuronal network [5] and quan

Aging differently affects cellular components of the brain active milieu. Here, we analyzed astrocytes and neurons in the neocortical access tissue of younger (22 - 50 years) and older (51 - 72 years) human who underwent resection of glioma or other cancer metastases to the brain. Aging decreased the amount of reduced mitochondrial cytochromes in astrocytes but not neurons. The protein-to-lipid ratio was decreased in astrocytes and increased in neurons. Aged astrocytes showed morphological dystrophy quantified by the decreased length of branches, decreased volume fraction of leaflets, and shri

…on synaptic transmission and intrinsic excitability. To understand changes in neuronal function by LGI1 encephalitis, we used patients’ serum IgGs or monoclonal a

…in memory modulation by regulating the excitability of hippocampal neurons, contributing to enhanced afterhyperpolarization (AHP). Calcium-activated potassium channels are fundamental modulators of neuronal excitability and contribute to the generation of AHPs following action potential bursts. TRPC3 channels enhance the activity of Ca2+-dependent K+ channels by local, microdomain communication.To uncover downstream targets of TRPC3 signaling in hippocampal neurons, we performed electrophysiological recordings,

…the engram depends on their relative excitability. Therefore, mechanisms regulating the balance between excitation (E) and inhibition (I) in the brain influence memory formation. Nogo-A negatively regulates neuronal plasticity and influences the E/I balance by promoting inhibitory, while suppressing excitatory synaptic transmission. Moreover, loss of function for Nogo-A result

…play a crucial role in modulating neuronal excitability in the central nervous system. Most pathogenic v

Disturbances to neuronal function at the level of the synapse are crucial features of neuropsychiatric disorders, such as schizophrenia. Synaptic dysfunction in the prefrontal cortex, and its consequences on neuronal circuitry and behaviour, have been extensively linked to the disease. In this study, we are characterising the functional and behavioural consequences of a recently discovered, schizophrenia-associated variant in the CACNG2 gene, coding for the postsynaptic protein stargazin (StgSCZ). The aim of our study is to uncover how dysfunction at the level of the synapse in the prefrontal

…modulation in humans by affecting neuronal excitability and plasticity, although the precise working mechanisms and optimal stimulation approaches are still unknown. Simultaneous functional brain network recording using magnetoencephalography (MEG) could enhance our understanding of the neurophysiological effects of tES and facilitate closed-loop neuromodulation.A concurrent tES-MEG session will be conducted in 20 adults without a ne

…altered synaptic plasticity and neuronal excitability associated with these mutations. Furthermore, behavioral assays in animal models harboring CYFIP2 mutations demonstrated phenotypes consistent with epileptic encephalopathy. These findings underscore the significance of CYFIP2 in neuronal d

…phosphatidylethanolamine; NAPE) on neuronal excitability of dorsal root ganglion (DRG) neurons and pain-like behavior using in vitro and in vivo experiments.Methods: Fluorescence imaging (Fura 2) of calcium changes in cultured DRG neurons with repeated high K+ (30 mM) pulses was used as an in vitro model of neuronal excitability. Intrathecal application of drugs in rats and subsequent measurement of thermal (Hargreaves test) and mechanical sensitivity (Von Frey test) was used to assess nocicept

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

…profoundly influencing neuronal excitability, synaptic transmission, and behavior. Their intricate interactions with the vascular system and diverse calcium signaling mechanisms further amplify their impact on brain functions. Our prior work has involved exploring spike-timing-dependent plasticity using a synapse model with astrocyte contributions (Manninen et al., 2020). Additionally, we have studied in detail existing astrocyte models tailored for various brain areas and functions (M

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

…on the possible relationship between excitability and neurodegeneration. Electrical activity was recorded at 37°C using the multielectrode array (MEA) technique in cerebral organoids prepared from induced pluripotent stem c

…expression related to neuroprotection, neuronal excitability, synaptic plasticity, and memory. N6-methyladenosine (m6A), the most abundant internal modification of RNA, influences mRNA stability, translation, transport, localization, and alternative splicing. This dynamic epitranscriptomic mark is prevalent in the nervous system, impacting various processes, including those affected by lactate, such as neurogenesis, synaptic

The neural control of sleep requires that sleep need is sensed during waking and discharged during sleep. While sleep loss has widespread consequences in the whole body and brain, perhaps the only realistic opportunity for separating causation from correlation exists in specialist neurons with active roles in sleep. To obtain an unbiased view of molecular changes in the brain underlying these processes, we characterized the transcriptomes of single sleep-control cells isolated from rested and sleep-deprived flies. Transcripts upregulated after sleep deprivation, in sleep-control neurons projec

The neuronal engram created during fear learning relies on both, plasticity of the neuronal network for its formation and the stability for persistence. The allocation of neurons to a specific engram depends on their excitability. Molecules regulating the excitation / inhibition balance (E/I balance) in the brain are therefore considered key players in engram formation. Nogo-A has been shown to influence the E/I balance, restrict activity-dependent functional and structural plasticity and modulate learning and memory formation. However, whether Nogo-A controls the memory engram formation and t

Altered neuronal excitability and synaptic inputs to motoneurons are part of the pathophysiology of Amyotrophic Lateral Sclerosis. The cAMP/PKA pathway regulates both of them but therapeutic interventions at this level are limited by the lack of knowledge about suitable pharmacological entry points. Here we used transcriptomics on microdissected and in situ motoneurons to reveal the modulation of PKA-coupled receptorome in SOD1(G93A) ALS mice, vs WT, demonstrating the dysregulation of multiple PKA-coupled GPCR, in particular on vulnerable MN, and the relative sparing of β-adrenergic. In vivo M

…plays a crucial role in shaping neuronal input-output function and is implicated in various neurological and psychiatric disorders. Despite its importance, the underlying molecular mechanisms of intrinsic plasticity remain poorly understood. Here, we identified a new ubiquitin ligase adaptor, protein tyrosine phosphatase receptor type N (PTPRN), as a regulator of intrinsic neuronal excitability in the context of temporal lobe epilepsy. We discovered that PTPRN facilitates NaV1.2 sodium channel en

…the mechanisms by which CaSR regulates neuronal function remain unexplored.We therefore studied how CaSR regulates neuronal excitability in t

Trehalose is a natural disaccharide formed by a 1,1-glycosidic bond between two α-glucose units, widely used in food industry due to its peculiar chemical properties. In the last 20 years the involuntary trehalose intake is exponentially increased, with unknown long-term effects on the population. Furthermore, circulating trehalose is able to reach the CNS. Importantly, trehalose induces autophagy in an mTORC1-independent manner activating the transcription factor EB (TFEB), the master transcriptional regulator of autophagy-lysosomal biogenesis. Accordingly, several studies indicated that treh

The prefrontal cortex plays a crucial role in cognitive functions such as decision making, planning, and working memory. It is subjected to strong monoaminergic neuromodulation, particularly by dopamine from the VTA. While dopamine innervations in the prefrontal cortex are sparse, recent research indicates that the vesicular dopamine transporter VMAT2 in astrocytes contributes to dopaminergic homeostasis in the prefrontal cortex. Here we hypothesized that astrocytes could provide a shuttle mechanism through which appropriate tonic levels of dopamine would be redistributed across the prefrontal