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Schlagwörter:
BK channels, dendritic spine, layer 5 pyramidal neuron, neocortex, neuronal modelling, potassium channels, pyramidal neuron, synaptic transmission, two-photon (2P) uncaging
Zusammenfassung:
Dendritic spines are the main receptacles of excitatory information in the brain. Their particular morphology, with a small head connected to the dendrite by a slender neck, has inspired theoretical and experimental work to understand how these structural features affect the processing, storage and integration of synaptic inputs in pyramidal neurons (PNs). The activation of glutamate receptors in spines triggers a large voltage change as well as calcium signals at the spine head. Thus, voltage-gated and calcium-activated potassium channels located in the spine head likely play a key role in synaptic transmission. Here we study the presence and function of large conductance calcium-activated potassium (BK) channels in spines from layer 5 PNs. We found that BK channels are localized to dendrites and spines regardless of their size, but their activity can only be detected in spines with small head volumes (≤0.09 μm3), which reduces the amplitude of two-photon uncaging excitatory postsynaptic potentials recorded at the soma. In addition, we found that calcium signals in spines with small head volumes are significantly larger than those observed in spines with larger head volumes. In accordance with our experimental data, numerical simulations predict that synaptic inputs impinging onto spines with small head volumes generate voltage responses and calcium signals within the spine head itself that are significantly larger than those observed in spines with larger head volumes, which are sufficient to activate spine BK channels. These results show that BK channels are selectively activated in small-headed spines, suggesting a new level of dendritic spine-mediated regulation of synaptic processing, integration and plasticity in cortical PNs. Key points BK channels are expressed in the visual cortex and layer 5 pyramidal neuron somata, dendrites and spines regardless of their size. BK channels are selectively activated in small-headed spines (≤0.09 μm3), which reduces the amplitude of two-photon (2P) uncaging excitatory postsynaptic potentials (EPSPs) recorded at the soma. Two-photon imaging revealed that intracellular calcium responses in the head of 2P-activated spines are significantly larger in small-headed spines (≤0.09 μm3) than in spines with larger head volumes. In accordance with our experimental data, numerical simulations showed that synaptic inputs impinging onto spines with small head volumes (≤0.09 μm3) generate voltage responses and calcium signals within the spine head itself that are significantly larger than those observed in spines with larger head volumes, sufficient to activate spine BK channels and suppress EPSPs.
