SK channels and NMDA receptors form a Ca2+-mediated feedback loop in dendritic spines

Ngo-Anh, Thu Jennifer; Bloodgood, Brenda L.; Lin, Michael; Sabatini, Bernardo L.; Maylie, James; Adelman, John P.

doi:10.1038/nn1449

Cited by 406 publications

(496 citation statements)

References 43 publications

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“…Previous studies have clearly demonstrated that NMDARdependent Ca 2ϩ influx is required for SK channel activation in CA1 neurons (17). Our present data suggest that RyR-mediated Ca 2ϩ release evoked by the Ca 2ϩ influx is important for SK channel activation.…”

Section: Discussionsupporting

confidence: 75%

“…Therefore, our observations indicate that the activation of SK channels requires NMDAR-mediated Ca 2ϩ influx in CA1 neurons, as reported in ref. 17. In JP-DKO neurons, APV had no significant effect on action potential configuration, suggesting the disconnection of functional communication between NMDARs and SK channels.…”

Section: Contribution Of Ca 2؉ Release For Sk Channel Activation and Itsmentioning

confidence: 92%

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Functional uncoupling between Ca ²⁺ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins

Moriguchi

Nishi

Komazaki

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Junctional membrane complexes (JMCs) composed of the plasma membrane and endoplasmic͞sarcoplasmic reticulum seem to be a structural platform for channel crosstalk. Junctophilins (JPs) contribute to JMC formation by spanning the sarcoplasmic reticulum membrane and binding with the plasma membrane in muscle cells. In this article, we report that mutant JP double-knockout (JP-DKO) mice lacking neural JP subtypes exhibited an irregular hindlimb reflex and impaired memory. Electrophysiological experiments indicated that the activation of small-conductance Ca 2؉ -activated K ؉ channels responsible for afterhyperpolarization in hippocampal neurons requires endoplasmic reticulum Ca 2؉ release through ryanodine receptors, triggered by NMDA receptor-mediated Ca 2؉ influx. We propose that in JP-DKO neurons lacking afterhyperpolarization, the functional communications between NMDA receptors, ryanodine receptors, and small-conductance Ca 2؉ -activated K ؉ channels are disconnected because of JMC disassembly. Moreover, JP-DKO neurons showed an impaired long-term potentiation and hyperactivation of Ca 2؉ ͞calmodulin-dependent protein kinase II. Therefore, JPs seem to have an essential role in neural excitability fundamental to plasticity and integrated functions.hippocampus ͉ learning and memory ͉ long-term potentiation ͉ ryanodine receptor ͉ SK channel F unctional communication between cell-surface and intracellular channels is an essential feature of excitable cells (1). During initiation of contraction in striated muscle cells, the activation of cell-surface dihydropyridine receptor (DHPRs) channels opens ryanodine receptors (RyRs) and triggers Ca 2ϩ release from the sarcoplasmic reticulum via either the ''Ca 2ϩ -induced Ca 2ϩ release'' or the ''voltage-induced Ca 2ϩ release'' mechanism (2). The functional couplings between the channels take place in junctional membrane complexes (JMCs), designated as the ''triad junction'' in skeletal muscle, ''diad'' in cardiac muscle, and ''peripheral coupling'' in immature striated and smooth muscles (3, 4). Recent studies indicated that junctophilin (JP) subtypes, namely JP-1-JP-4, contribute to JMC formation in muscle cells (5, 6). In JP-1 knockout mice with perinatal lethality, mutant skeletal muscle shows deficiency of triad junctions and insufficient contraction probably caused by impaired communication between DHPRs and RyRs (7). In JP-2 knockout embryos showing cardiac arrest, mutant cardiac myocytes exhibit deficiency of peripheral couplings and arrhythmic Ca 2ϩ signaling probably caused by functional uncoupling between DHPRs and RyRs (5). In the brain, both JP-3 and JP-4 are expressed in similar discrete neuronal sites and may collaboratively contribute to JMC formation (8, 9). However, the role of neural JP subtypes is largely unknown. Using knockout mice lacking both JP-3 and JP-4 (JP-DKO mice), we report their essential contributions to the tuning of excitability and plasticity in hippocampal pyramidal neurons. ResultsGeneration of JP-DKO Mice Bearing Lethality. JP-4 knockou...

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Section: Discussionsupporting

confidence: 75%

Section: Contribution Of Ca 2؉ Release For Sk Channel Activation and Itsmentioning

confidence: 92%

Functional uncoupling between Ca ²⁺ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins

Moriguchi

Nishi

Komazaki

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…SK channels can regulate numerous aspects of neuronal dynamics including: spike frequency adaptation (Pedarzani et al, 2005), dendrosomatic coupling (Cai et al, 2004), as well as synaptic integration and potentiation (Faber et al, 2005;Ngo-Anh et al, 2005). The links between SK channel kinetics and behaviourally relevant neuronal computations have only recently begun to be examined for the SK2 subtype (Ellis et al, 2007b).…”

Section: Sk2 Channels Contribute To Tuning Differences Observed Acrosmentioning

confidence: 99%

Ionic and neuromodulatory regulation of burst discharge controls frequency tuning

Mehaffey

Ellis

Krahe

et al. 2008

Journal of Physiology-Paris

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Sensory neurons encode natural stimuli by changes in firing rate or by generating specific firing patterns, such as bursts. Many neural computations rely on the fact that neurons can be tuned to specific stimulus frequencies. It is thus important to understand the mechanisms underlying frequency tuning. In the electrosensory system of the weakly electric fish, Apteronotus leptorhynchus, the primary processing of behaviourally relevant sensory signals occurs in pyramidal neurons of the electrosensory lateral line lobe (ELL). These cells encode low frequency prey stimuli with bursts of spikes and high frequency communication signals with single spikes. We describe here how bursting in pyramidal neurons can be regulated by intrinsic conductances in a cell subtype specific fashion across the sensory maps found within the ELL, thereby regulating their frequency tuning. Further, the neuromodulatory regulation of such conductances within individual cells and the consequences to frequency tuning are highlighted. Such alterations in the tuning of the pyramidal neurons may allow weakly electric fish to preferentially select for certain stimuli under various behaviourally relevant circumstances.

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“…First, active conductances, including calcium (2), potassium (11), and probably even sodium (12) channels, seem to be located in spines, rendering passive models inadequate to explore the effect of the spine on EPSPs. Second, spines with different morphologies have differences in calcium compartmentalization (13) and in amplitude and kinetics in response to glutamate uncaging (14), raising the suspicion that the spine neck has a major functional role.…”

mentioning

confidence: 99%

Imaging membrane potential in dendritic spines

Nuriya

Jiang

Nemet

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

171

146

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Dendritic spines mediate most excitatory inputs in the brain. Although it is clear that spines compartmentalize calcium, it is still unknown what role, if any, they play in integrating synaptic inputs. To investigate the electrical function of spines directly, we used second harmonic generation (SHG) imaging of membrane potential in pyramidal neurons from hippocampal cultures and neocortical brain slices. With FM 4-64 as an intracellular SHG chromophore, we imaged membrane potential in the soma, dendritic branches, and spines. The SHG response to voltage was linear and seemed based on an electro-optic mechanism. The SHG sensitivity of the chromophore in spines was similar to that of the parent dendritic shaft and the soma. Backpropagation of somatic action potentials generated SHG signals at spines with similar amplitude and kinetics to somatic ones. Our optical measurements of membrane potential from spines demonstrate directly that backpropagating action potentials invade the spines.second-harmonic imaging ͉ backpropagation ͉ action potential ͉ pyramidal ͉ cortex S pines mediate most excitatory contact in the mammalian nervous system, so they are likely to be crucial for brain function (1). Although their role in calcium compartmentalization has been demonstrated (2), nonspiny neurons can also compartmentalize calcium with similar spatial restriction (3), so it is likely that spines serve additional functions in dendritic integration. In particular, there is a long-standing controversy related to the electrical function of dendritic spines (4). On the one hand, it has been argued that spines could have a significant effect on the excitatory postsynaptic potentials (EPSPs) (5-7). Spines could either enhance the depolarization generated by EPSPs (8) or even filter and dampen EPSPs, as they are transmitted to the dendritic shaft or the soma. ¶ On the other hand, cable models constrained by morphological or diffusional measurements indicate that spines may not play a significant electrical role (9, 10). Thus, assuming a passive membrane, the spine neck could have a negligible effect in altering the EPSPs, so spines may play no significant electrical role and merely serve as biochemical compartments.Recent data have reopened this debate and suggest that spines could have a significant effect on altering synaptic transmission. First, active conductances, including calcium (2), potassium (11), and probably even sodium (12) channels, seem to be located in spines, rendering passive models inadequate to explore the effect of the spine on EPSPs. Second, spines with different morphologies have differences in calcium compartmentalization (13) and in amplitude and kinetics in response to glutamate uncaging (14), raising the suspicion that the spine neck has a major functional role.Direct measurement of electrical function of spine has eluded scientists due to lack of suitable experimental approaches. Although fluorescent voltage-sensitive dyes have been used to image dendrites (15), their lack of sensitivity, partly resulti...

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SK channels and NMDA receptors form a Ca2+-mediated feedback loop in dendritic spines

Cited by 406 publications

References 43 publications

Functional uncoupling between Ca ²⁺ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins

Functional uncoupling between Ca ²⁺ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins

Ionic and neuromodulatory regulation of burst discharge controls frequency tuning

Imaging membrane potential in dendritic spines

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SK channels and NMDA receptors form a Ca2+-mediated feedback loop in dendritic spines

Cited by 406 publications

References 43 publications

Functional uncoupling between Ca 2+ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins

Functional uncoupling between Ca 2+ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins

Ionic and neuromodulatory regulation of burst discharge controls frequency tuning

Imaging membrane potential in dendritic spines

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Functional uncoupling between Ca ²⁺ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins

Functional uncoupling between Ca ²⁺ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins