Synaptic transmission

…spikes for short) that modulate synaptic transmission, blurring the line between analog and digital signaling. In this study, we consider a model of a binomial synapse, where the probability of vesicle release is determined by a product of two factors: a binary indicator of presynaptic spiking, and a contin

Recent years have witnessed a growing body of experimental evidence highlighting the active role of glial cells in modulating neuronal dynamics. Glial cells, including astrocytes and microglia, have been found to influence various aspects of neuronal function, such as regulating neurotransmitter concentrations and ion buffering. Yet, the mechanisms through which glial cells communicate with and affect neighboring neurons remain unclear. In this study, we seek to develop a computational model to explore recent experimental findings which demonstrated that glial cells physically wrap around, o

Body size varies across 21 orders of magnitudes in the animal kingdom [1]. In contrast to most organs, which scale through the proliferation of dividing cells of similar size, brains expand by modulating the size of non-dividing neuronal cells to innervate space during development [2]. Consequently, there is a notable variation in neuronal size and structure within individual brains and across species [3]. Considering that size inherently affects the rates of biological structures and processes, from cellular metabolism to information processing [4], the ability of neurons to maintain essentia

…In our study, we investigate synaptic transmission in terms of an optimization problem, where the space of solutions comprises the digital and the analog regime. We analyze a binomial synapse model connecting two neurons, where the probability of transmitter release, modeled by a transfer function, depends on the axonal membrane potential. We optimize the transfer f

…Changes in synaptic function precede neurodegeneration, and this extracellular α-synuclein can affect synaptic transmission. However, whether and how the spreading of α-synuclein aggregates modulates synaptic function before neuronal loss remains unknown. In the present study, we investigated the effect of intrastriatal injection of α-synuc

Neurofibromatosis type 1 (NF1) is a genetic disorder caused by reduction or absence of neurofibromin due to mutations in the NF1 gene that result in multiple behavioral defects among other aberrant phenotypes. To directly assess the consequences of Nf1 deficiency on evoked neuronal activity, potentially underlying neuroplasticity defects, we utilized null mutations, point mutations, and RNA interference to manipulate Nf1 levels in Drosophila melanogaster. Our study focused on assessing the functional alterations in the giant fiber system, a well-established electrophysiological model to study

N-methyl-D-aspartate receptors (NMDARs) are key players in synaptic transmission and plasticity underlying learning and memory. Consequently, synaptic dysfunction of NMDARs has been implicated in the pathophysiology of Alzheimer´s disease (AD).Aims: to unravel possible alterations of GluN1, the obligatory subunit of NMDARs, in different excitatory synapses in the hippocampus.Methods: We used histoblot and SDS-digested freeze-fracture replica labelling (SDS-FRL) techniques.Results: Histoblots showed that GluN1 expression was significantly reduced in the caudate putamen, cortex and in the hippoc

…also regulate the activity of local synaptic circuits through secretion and clearance of neurotransmitters. Whilst the molecular signal exchange between astroglia and synapses occurs in a highly heterogeneous microenvironment on the nanoscale, the spatial subcellular distribution of the underlying molecular machineries remains poorly understood. Similarly, in addition to clo

Theta oscillations (4-12 Hz) in the hippocampus are caused by the synchronous bursting activity of neuronal populations. They are critical for grouping and selecting neuronal ensembles in the context of spatial navigation, memory, and learning, but the reason why this frequency band is particularly effective for adjusting neuronal ensembles remains speculative. Here we show that burst activity at the CA3-CA1 synapse of the mouse hippocampus leads to a rapid activation of astrocytic leaflets possibly via the retrograde release of endocannabinoids that activate transient receptor potential chann

…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

…expression has been linked to abnormal synaptic transmission and improper dendritic spines morphogenesis, which are tough to underlies the bulk of the cognitive and behavioral defects exhibited by FXS patients. However, our current understanding of FXS physiopathology

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease that causes the degeneration of motor neurons in the motor cortex and spinal cord. Patients with ALS experience muscle weakness and atrophy in the limbs which eventually leads to paralysis and death. NAD+ is critical for energy metabolism, such as glycolysis and oxidative phosphorylation, but is also involved in non-metabolic cellular reactions. In the current study, we determined whether the supplementation of nicotinamide mononucleotide (NMN), an NAD+ precursor, in the diet had beneficial impacts on disease progr

Voltage-gated CaV2.1 Ca2+ channels play a crucial role in regulating neurotransmitter release, thus contributing to processes such as learning and memory. Despite their recognised importance in neural function, there is limited information on their potential involvement in neurodegenerative conditions such as Alzheimer's disease (AD). Aims: to explore the impact of amyloid-β (Aβ) pathology on the nanoscale compartmentalization of CaV2.1-GABAB in the hippocampus.Methods: We used histoblot and SDS-digested freeze-fracture replica labelling (SDS-FRL) techniques in the CA1 field of the hippocampus

…a peptide that is known to weaken synaptic transmission. Whereas both AMPA receptor (AMPAR) and NMDA receptor (NMDAR) currents are affected by Aβ oligomers, not all synapses are equally vulnerable to the toxic effects of Aβ. We set out to elucidate the roles of the different AMPAR and NMDAR subunits in synapse susceptibility to Aβ. Whole-cell patch clamp recordings were performed in hippocampal CA1 neurons that overexpress Aβ oligomers. Variance analysis was used to disentangle whether this decreased syna

…in the mammalian brain and the synaptic transcriptome. m6A methylation is dynamically regulated by enzymes called m6A writers (METTL3/14) and erasers (FTO), that are present in distal neuronal processes. Although recent studies link dynamic m6A methylome changes during synaptic plasticity to memory consolidation, the exact mechanisms in neuronal circuits remain unclear. This study investigates m6A methylation effects on synaptic transmission and plasticity within hippocampal networks, utilizing p

Perfluorinated compounds (PFCs) are organofluorine compounds containing carbon-fluorine and carbon-carbon bonds. They are used as water and oil repellants in clothes and pharmaceutical tablets, but have been found to cause neurotoxicity. However, it remains elusive whether PFCs affect neural survival or activity, or whether they alter different neuronal regulations in the brain. Additionally, there is a paucity of data on the regulatory mechanisms involved in PFCs-induced neural toxicity.In the current study, we report that PFOA or PFHpA differentially alter neural survival and activity in pri

Astrocytes have a pivotal role in overseeing extracellular ion concentrations and synaptic neurotransmitters, 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

…calcium that plays critical roles in synaptic transmission, synaptogenesis, and plasticity. Recent sequencing data in neurological and psychiatric patients reveal numerous variants in genes encoding NMDAR subunits. In our study, we have created and evaluated a transgenic mouse line carrying a frameshift variant (Grin2b L825FfsX4) resulting in the deletion of about half of the GluN2B subunit. Our methods included patch-clamp recordings from hippocampal neurons in both wild-type (Grin2bWT/WT) and transgenic (Grin

…out long-lasing rescue effects on synaptic deficits and behavioral abnormalities. The other study, however, clai

…which allows the formation of trans-synaptic bridges, and triggers transmembrane signaling. We recently reported a homozygous missense variants of GRID1, p.Arg161His, associated with combined intellectual disability, spastic paraplegia and glaucoma. In vitro studies revealed that this mutation hampers metabotropic glutamate receptor mGlu1/5 s

…in impairments of multiple aspects of synaptic transmission, neuronal connectivity, and activity patterns. Dysfunctions of the dopaminergic circuitry were already postulated several decades ago. Patients with SCZ suffer from disturbances in the reward system, as well as in executive and cognitive functions. The two dopaminergic pathways, mesolimbic and mesocortical, have been implicated in neuropsychiatric disorders. Both originate from the ventral tegmental area and project to th

…exocytosis, thus contributing to synaptic transmission. Intriguingly, ASIC1-dependent current was small compared to currents of GABA or Glutamate receptors, however, ASIC1 was reported to have a significant impact on various physiological and pathophysiological processes e.g. fear related behavior, lo

…learning and memory, ii) hippocampal synaptic transmission and plasticity, and iii) gene expression of glutamatergic and hormone rec

…vital role in memory consolidation and synaptic plasticity [1]. Our recent research revealed a novel role for Arc/Arg3.1 in developing brain circuits. In the hippocampus, a spontaneous wave of Arc/Arg3.1 upregulation is observed during the first postnatal month, crucial for establishing proper spatial learning and intact hippocampal oscillations in adult mice [2]. Since the emergence of hippocampal oscillatory rhythms relies on an intricate interplay between excitatory and inhibitory synaptic connections, we hypothesized that early postna