Selective activation of BK channels in small‐headed dendritic spines suppresses excitatory postsynaptic potentials. (9th March 2022)

• Record Type: Journal Article
• Authors: Tazerart, Sabrina; Blanchard, Maxime G.; Miranda‐Rottmann, Soledad; Mitchell, Diana E.; Navea Pina, Bruno; Thomas, Connon I.; Kamasawa, Naomi; Araya, Roberto
• Is Part Of: Journal of physiology. Volume 600:Number 9(2022)
• Page Start: 2165
• Page End: 2187
• Publication Date: 2022-03-09
• Subjects: BK channels -- dendritic spine -- layer 5 pyramidal neuron -- neocortex -- neuronal modelling -- potassium channels -- pyramidal neuron -- synaptic transmission -- two‐photon (2P) uncaging; Physiology -- Periodicals; 612.005
• DOI: 10.1113/JP282303
• Languages: English
• ISSNs: 0022-3751

Abstract

Abstract : Abstract: 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 μm 3 ), 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 μm 3 ), 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 μm 3 ) 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 μm 3 ) 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. Abstract : Abstract figure legend The dendrites of cortical pyramidal neurons are covered by tiny protrusions called dendritic spines, the main recipients of excitatory inputs in the brain. Their passive (morphological) and active (activation of voltage‐gated channels) properties during synaptic transmission are ill‐defined. Synaptic activation of spines can trigger large voltage swings and calcium increases in the spine head. Here we studied the presence of voltage‐gated and calcium‐activated potassium (BK) channels in dendrites and their role in excitatory synaptic transmission. We used two‐photon uncaging of glutamate, which mimics synaptic transmission, to activate single spines and found that BK channels are present in spines of different morphologies but are selectively activated in small‐headed dendritic spines, effectively suppressing excitatory postsynaptic potentials in layer 5 pyramidal neurons.