Biology subjects

Kopach, O.

Publications and source records attributed to Kopach, O..

4 recordsLinked to original sources

bioRxiv2026

Sensory experience drives glutamate spillover, presynaptic LTP and functional connectome remodeling in the barrel cortex

Information handling and storage by neural circuits is thought to involve dynamic changes in the synaptic connectome, yet how this process unfolds at the level of individual synapses in vivo remains unclear. We took advantage of a well-defined thalamocortical anatomical framework to monitor identifiable individual synapses in barrel cortex during rhythmic whisker stimulation (RWS). Multiplexed ratiometric readouts from genetically targeted optical sensors showed that RWS-induced long-term potentiation (LTP) increased glutamate release per action potential in RWS-responsive axons while recruiting previously silent thalamocortical connections. Fast high-resolution imaging revealed pronounced inter-synaptic glutamate transients and global extracellular GABA waves triggered by brief RWS. LTP induction had no detectable effect on the evoked GABA signal but further enhanced glutamate crosstalk beyond thalamocortical synapses. Strikingly, neural-network simulations suggest that such volume-transmitted excitatory signals can improve associative memory retrieval in sparsely connected networks. Together, these findings uncover key plasticity features of the cortical synaptic connectome and point to a potential computational consequence of glutamate spillover for brain circuit function.

neuroscience↗

bioRxiv2024

Alpha-synuclein aggregates trigger anti-viral immune pathways and RNA editing in human astrocytes

RNA editing is a post transcriptional mechanism that targets changes in RNA transcripts to modulate innate immune responses. We report the role of astrocyte specific, ADAR1 mediated RNA editing in neuroinflammation in Parkinsons disease. We generated hiPSC-derived astrocytes, neurons and co-cultures and exposed them to small soluble alpha-synuclein aggregates. Oligomeric alpha-synuclein triggered an inflammatory glial state associated with TLR activation, viral responses, and cytokine secretion. This reactive state resulted in loss of neurosupportive functions, and the induction of neuronal toxicity. Notably, interferon response pathways were activated leading to upregulation, and isoform switching of the RNA deaminase enzyme, ADAR1. ADAR1 mediates A-to-I RNA editing, and increases in RNA editing were observed in inflammatory pathways in cells, as well as in post-mortem human PD brain. Aberrant, or dysregulated, ADAR1 responses and RNA editing may lead to sustained inflammatory reactive states in astrocytes triggered by alpha-synuclein aggregation, and this may drive the neuroinflammatory cascade in Parkinsons.

neuroscience↗

bioRxiv2022

Blood cells communicate remotely via an NMDA receptor-mediated glutamatergic chain-reaction

Neutrophils are white blood cells that are critical to the acute inflammatory and adaptive immune responses. Their swarming-pattern behaviour is controlled by multiple cellular cascades involving calcium-dependent release of various signalling molecules. Previous studies have reported that neutrophils express glutamate receptors and can release glutamate but evidence of direct neutrophil-neutrophil communication has been elusive. Here, we hold semi-suspended cultured human neutrophils in patch-clamp whole-cell mode to find that calcium mobilisation induced by stimulating one neutrophil can trigger an NMDA receptor-driven membrane current and calcium signal in neighbouring neutrophils. We employ an enzymatic-based imaging assay to image, in real time, glutamate release from neutrophils induced by glutamate released from their neighbours. These observations provide direct evidence for a positive-feedback inter-neutrophil communication that could contribute to mechanisms regulating communal neutrophil behaviour.

cell biology↗

bioRxiv2020

Release probability increases towards distal dendrites boosting high-frequency signal transfer

Dendritic integration of synaptic inputs entangles their increased electrotonic attenuation at distal dendrites, which can be counterbalanced by the increased synaptic receptor density. However, during sustained network activity the influence of individual synapses depends on their release properties. How these properties are distributed along dendrites remains poorly understood. Here, we employed classical optical quantal analyses and a genetically encoded optical glutamate sensor in acute hippocampal slices to monitor release at CA3-CA1 synapses. We find that their release probability increases with greater distances from the soma. Similar-fidelity synapses tend to group together whereas release probability shows no trends regarding the within-branch position. Simulations with a realistic CA1 pyramidal cell hosting stochastic synapses suggest that the observed trends boost signal transfer fidelity, particularly at higher input frequencies. Because high-frequency bursting has been associated with learning, the release probability pattern we have found may play a key role in memory trace formation.

neuroscience↗