scholarly journals Selective activation of BK channels in small-headed dendritic spines suppresses excitatory postsynaptic potentials

2021 ◽  
Author(s):  
Sabrina Tazerart ◽  
Maxime G. Blanchard ◽  
Soledad Miranda-Rottmann ◽  
Diana E. Mitchell ◽  
Bruno Navea Pina ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Pyramidal Neurons ◽  
Structural Features ◽  
Bk Channels ◽  
Excitatory Postsynaptic Potentials ◽  
Calcium Signals ◽  
Postsynaptic Potentials ◽  
Synaptic Inputs ◽  
Spine Head ◽  
Small Head

AbstractDendritic 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 find 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 (2P) uncaging (u) excitatory postsynaptic potentials (EPSPs) recorded at the soma. In addition, we find 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 bigger 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.

scholarly journals Ketamine disinhibits dendrites and enhances calcium signals in prefrontal dendritic spines

2019 ◽  
Author(s):  
Farhan Ali ◽  
Danielle M. Gerhard ◽  
Katherine Sweasy ◽  
Santosh Pothula ◽  
Christopher Pittenger ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Dendritic Spines ◽  
Pyramidal Neurons ◽  
Gabaergic Neurons ◽  
Calcium Transients ◽  
Inhibitory Mechanism ◽  
Calcium Signals ◽  
Synaptic Inputs ◽  
Aspartate Receptor ◽  
Antidepressant Effects

AbstractA subanesthetic dose of ketamine causes acute psychotomimetic symptoms and then more sustained antidepressant effects. A key targeted brain region is the prefrontal cortex, and the prevailing disinhibition hypothesis posits that N-methyl-d-aspartate receptor (NMDAR) antagonists such as ketamine may act preferentially on GABAergic neurons. However, cortical GABAergic neurons are heterogeneous. In particular, somatostatin-expressing (SST) interneurons selectively inhibit dendrites and regulate synaptic inputs, yet their response to systemic NMDAR antagonism is unknown. Here, we report that administration of ketamine acutely suppresses the activity of SST interneurons in the medial prefrontal cortex of the awake mouse. The deficient dendritic inhibition leads to greater synaptically evoked calcium transients in the apical dendritic spines of pyramidal neurons. By manipulating NMDAR signaling via GluN2B knockdown, we show that ketamine’s actions on the dendritic inhibitory mechanism has ramifications for frontal cortex-dependent behaviors and cortico-cortical connectivity. Collectively, these results demonstrate dendritic disinhibition and elevated calcium levels in dendritic spines as important local-circuit alterations driven by the administration of subanesthetic ketamine.

Neuronal Activity Regulates Diffusion Across the Neck of Dendritic Spines

Science ◽  
2005 ◽  
Vol 310 (5749) ◽  
pp. 866-869 ◽  
Author(s):  
Brenda L. Bloodgood ◽  
Bernardo L. Sabatini
Keyword(s):  
Neuronal Activity ◽  
Dendritic Spines ◽  
Action Potentials ◽  
Synaptic Activation ◽  
Postsynaptic Potentials ◽  
Electrical Isolation ◽  
Spine Head ◽  
Postsynaptic Action ◽  
Excitatory Neurons

In mammalian excitatory neurons, dendritic spines are separated from dendrites by thin necks. Diffusion across the neck limits the chemical and electrical isolation of each spine. We found that spine/dendrite diffusional coupling is heterogeneous and uncovered a class of diffusionally isolated spines. The barrier to diffusion posed by the neck and the number of diffusionally isolated spines is bidirectionally regulated by neuronal activity. Furthermore, coincident synaptic activation and postsynaptic action potentials rapidly restrict diffusion across the neck. The regulation of diffusional coupling provides a possible mechanism for determining the amplitude of postsynaptic potentials and the accumulation of plasticity-inducing molecules within the spine head.

scholarly journals Calcium dynamics in single spines during coincident pre- and postsynaptic activity depend on relative timing of back-propagating action potentials and subthreshold excitatory postsynaptic potentials

1998 ◽  
Vol 95 (16) ◽  
pp. 9596-9601 ◽  
Author(s):  
Helmut J. Koester ◽  
Bert Sakmann
Keyword(s):  
Action Potentials ◽  
Pyramidal Neurons ◽  
Small Time ◽  
Time Interval ◽  
Relative Timing ◽  
Excitatory Postsynaptic Potentials ◽  
Postsynaptic Potentials ◽  
Postsynaptic Activity ◽  
Basal Dendrites ◽  
Dendritic Shaft

We compared the transient increase of Ca2+ in single spines on basal dendrites of rat neocortical layer 5 pyramidal neurons evoked by subthreshold excitatory postsynaptic potentials (EPSPs) and back-propagating action potentials (APs) by using calcium fluorescence imaging. AP-evoked Ca2+ transients were detected in both the spines and in the adjacent dendritic shaft, whereas Ca2+ transients evoked by single EPSPs were largely restricted to a single active spine head. Calcium transients elicited in the active spines by a single AP or EPSP, in spines up to 80 μm for the soma, were of comparable amplitude. The Ca2+ transient in an active spine evoked by pairing an EPSP and a back-propagating AP separated by a time interval of 50 ms was larger if the AP followed the EPSP than if it preceded it. This difference reflected supra- and sublinear summation of Ca2+ transients, respectively. A comparable dependence of spinous Ca2+ transients on relative timing was observed also when short bursts of APs and EPSPs were paired. These results indicate that the amplitude of the spinous Ca2+ transients during coincident pre- and postsynaptic activity depended critically on the relative order of subthreshold EPSPs and back-propagating APs. Thus, in neocortical neurons the amplitude of spinous Ca2+ transients could encode small time differences between pre- and postsynaptic activity.

scholarly journals Ketamine disinhibits dendrites and enhances calcium signals in prefrontal dendritic spines

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Farhan Ali ◽  
Danielle M. Gerhard ◽  
Katherine Sweasy ◽  
Santosh Pothula ◽  
Christopher Pittenger ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Dendritic Spines ◽  
Pyramidal Neurons ◽  
Gabaergic Neurons ◽  
Calcium Transients ◽  
Inhibitory Mechanism ◽  
Synaptic Inputs ◽  
Aspartate Receptor ◽  
Antidepressant Effects ◽  
Cortical Interneurons

AbstractA subanesthetic dose of ketamine causes acute psychotomimetic symptoms and sustained antidepressant effects. In prefrontal cortex, the prevailing disinhibition hypothesis posits that N-methyl-d-aspartate receptor (NMDAR) antagonists such as ketamine act preferentially on GABAergic neurons. However, cortical interneurons are heterogeneous. In particular, somatostatin-expressing (SST) interneurons selectively inhibit dendrites and regulate synaptic inputs, yet their response to systemic NMDAR antagonism is unknown. Here, we report that ketamine acutely suppresses the activity of SST interneurons in the medial prefrontal cortex of the awake mouse. The deficient dendritic inhibition leads to greater synaptically evoked calcium transients in the apical dendritic spines of pyramidal neurons. By manipulating NMDAR signaling via GluN2B knockdown, we show that ketamine’s actions on the dendritic inhibitory mechanism has ramifications for frontal cortex-dependent behaviors and cortico-cortical connectivity. Collectively, these results demonstrate dendritic disinhibition and elevated calcium levels in dendritic spines as important local-circuit alterations driven by the administration of subanesthetic ketamine.

scholarly journals Nicotinic and Muscarinic Reduction of Unitary Excitatory Postsynaptic Potentials in Sensory Cortex; Dual Intracellular Recording In Vitro

2006 ◽  
Vol 95 (4) ◽  
pp. 2155-2166 ◽  
Author(s):  
Robert B. Levy ◽  
Alex D. Reyes ◽  
Chiye Aoki
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Pyramidal Neurons ◽  
Glutamate Release ◽  
Receptor Activation ◽  
Nmda Receptor Antagonist ◽  
Excitatory Postsynaptic Potentials ◽  
Postsynaptic Potentials ◽  
Sensory Activity

We studied the cholinergic modulation of glutamatergic transmission between neighboring layer 5 regular-spiking pyramidal neurons in somatosensory cortical slices from young rats (P10-P26). Brief bath application of 5–10 μM carbachol, a nonspecific cholinergic agonist, decreased the amplitude of evoked unitary excitatory postsynaptic potentials (EPSPs). This effect was blocked by 1 μM atropine, a muscarinic receptor antagonist. Nicotine (10 μM), in contrast to carbachol, reduced EPSPs in nominally magnesium-free solution but not in the presence of 1 mM Mg+2, indicating the involvement of NMDA receptors. Likewise, when the postsynaptic cell was depolarized under voltage clamp to allow NMDA receptor activation in the presence of 1 mM Mg+2, synaptic currents were reduced by nicotine. Nicotinic EPSP reduction was prevented by the NMDA receptor antagonist d-AP5 (50 μM) and by the nicotinic receptor antagonist mecamylamine (10 μM). Both carbachol and nicotine reduced short-term depression of EPSPs evoked by 10 Hz stimulation, indicating that EPSP reduction happens via reduction of presynaptic glutamate release. In the case of nicotine, several possible mechanisms for NMDAR-dependent EPSP reduction are discussed. As a result of NMDA receptor dependence, nicotinic EPSP reduction may serve to reduce the local spread of cortical excitation during heightened sensory activity.

Excitatory postsynaptic potentials recorded from regular-spiking cells in layers II/III of rat sensorimotor cortex

1992 ◽  
Vol 67 (3) ◽  
pp. 728-737 ◽  
Author(s):  
G. G. Hwa ◽  
M. Avoli
Keyword(s):  
Nmda Receptor Antagonist ◽  
Short Latency ◽  
Neuronal Membrane ◽  
Dependent Manner ◽  
Excitatory Postsynaptic Potentials ◽  
Normal Medium ◽  
Postsynaptic Potentials ◽  
Extracellular Stimuli ◽  
Relationship Of

1. Intracellular recording techniques were used to investigate the physiological and pharmacological properties of stimulus-induced excitatory postsynaptic potentials (EPSPs) recorded in regular-spiking cells located in layers II/III of rat sensorimotor cortical slices maintained in vitro. 2. Depending on the strength of the extracellular stimuli, a pure EPSP or an EPSP-inhibitory postsynaptic potential sequence was observed under perfusion with normal medium. The EPSPs displayed short latency of onset [2.4 +/- 0.7 (SD) ms] and were able to follow repetitive stimulation (tested less than or equal to 5 Hz). Variation of the membrane potential (Vm) revealed two types of voltage behavior for the short-latency EPSP. The first type decreased in amplitude with depolarization and increased in amplitude with hyperpolarization. In contrast, the second type behaved anomalously by increasing and decreasing in size after depolarization and hyperpolarization, respectively. 3. Several experimental procedures were carried out to investigate the mechanism underlying the anomalous voltage behavior of the EPSP. Results indicated that this type of Vm dependency could be mimicked by an intrinsic response evoked by a brief pulse of depolarizing current and could be abolished by N-(2,6-dimethylphenylcarbamoylmethyl)triethylammonium bromide (50 mM). Furthermore, the EPSP was not sensitive to the N-methyl-D-aspartate (NMDA) receptor antagonist 3-((+-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate (CPP, 10 microM). Thus the anomalous voltage relationship of the neuronal membrane. 4. The involvement of non-NMDA receptors in excitatory synaptic transmission was investigated with their selective antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 1-10 microM). This drug greatly reduced or completely blocked the EPSP in a dose-dependent manner (1-10 microM). The IC50 for the CNQX effect was approximately 2 microM. In the presence of CNQX (10 microM) and glycine (10 microM), synaptic stimulation failed to elicit firing of action potential. However, a CPP-sensitive EPSP was observed. 5. When synaptic inhibition was reduced by low concentration of bicuculline methiodide (BMI, 1-2 microM), extracellular stimulation revealed late EPSPs (latency to onset: 10-30 ms) that were not discernible in normal medium. Similar to the short-latency EPSP, the Vm dependency displayed by this late EPSP could be modified by inward membrane rectifications. The late EPSP appeared to be polysynaptic in origin because 1) its latency of onset was long and variable and 2) it failed to follow repetitive stimuli delivered at a frequency that did not depress the short-latency EPSP.(ABSTRACT TRUNCATED AT 400 WORDS)

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