Spontaneous Axonal ER Ca2+ Waves Mediate A Shift From Action Potential-Dependent to Independent Glutamate Release in the YAC128 HD-Model
Mackay, J. P.; Buren, C.; Smith-Dijak, A. I.; Koch, E. T.; Zhang, P.; Schmidt, M.; Fung, E.; Nassrallah, W. B.; Hayden, M. R.; Raymond, L. A.
Show abstract
Action potential-independent (miniature) neurotransmission occurs at all chemical synapses, but remains poorly understood, particularly in pathological contexts. Spontaneous release of Ca2+ from the axonal endoplasmic reticulum (ER) is thought to facilitated miniature neurotransmission, and aberrant ER Ca2+ handling is notably implicated in the progression of Huntingtons disease (HD) and other neurodegenerative diseases. Here, we report elevated glutamate-mediated miniature synaptic event frequencies in YAC128 (HD-model) cortical neurons, which pharmacological experiments suggest is mediated by enhanced spontaneous ER Ca2+ release. Calcium imaging using an axon-localized sensor revealed slow action potential (AP)-independent axonal Ca2+ waves, which were more common in YAC128 cortical neurons. Conversely, spontaneous axonal ER Ca2+ release was associated with reduced AP-dependent axonal Ca2+ events and consequent glutamate release. Together, our results suggest spontaneous release of axonal ER Ca2+ stores oppositely regulates activity-dependent and -independent neurotransmitter release in HD, with potential implications for the fidelity and plasticity of cortical excitatory signaling.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- α2δ-2 protein controls structure and function at the cerebellar climbing fiber synapse 97%
- Synaptotagmin 9 modulates spontaneous neurotransmitter release in striatal neurons by regulating substance P secretion 96%
- Delaying the GABA shift indirectly affects membrane properties in the developing hippocampus 96%
Similar papers in this journal
- Dopaminergic neuromodulation of spike timing dependent plasticity in mature adult rodent and human cortical neurons 96%
- Depolarizing GABA Transmission Restrains Activity-Dependent Glutamatergic Synapse Formation in the Developing Hippocampal Circuit 96%
- Neurotransmitter content heterogeneity within an interneuron class shapes inhibitory transmission at a central synapse 96%
Similar papers in this journal
- Progressive circuit hyperexcitability in mouse neocortical slice cultures with increasing duration of activity silencing 97%
- Prolonged activity-deprivation causes pre- and postsynaptic compensatory plasticity at neocortical excitatory synapses 96%
- Cell-type specificity of neuronal excitability and morphology in the central amygdala 96%
Similar papers in this journal
- Impaired dendritic spike generation in the Fragile X prefrontal cortex is due to loss of dendritic sodium channels 97%
- Cation-chloride cotransporters and the polarity of GABA signaling in mouse hippocampal parvalbumin interneurons 96%
- Astrocytic modulation of information processing by layer 5 pyramidal neurons of the mouse visual cortex 96%
Similar papers in this journal
- Endosomal sorting protein SNX4 limits synaptic vesicle docking and release 97%
- GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals 96%
- Distinct release properties of glutamate/GABA co-transmission serve as a frequency-dependent filtering of supramammillary inputs 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.