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Ca2+-activated K+ channels (BK and SK) are ubiquitous in synaptic circuits, but their role in network adaptation and sensory perception remains largely unknown. Using electrophysiological and behavioral assays and biophysical modelling, we discover how visual information transfer in mutants lacking the BK channel (dSlo-), SK channel (dSK-) or both...
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... 1965;Laughlin et al., 1998;Skou, 1998). For these estimates, we generated 405 two separate photoreceptor membrane models: a conservative one (Table 1; containing the known 406 voltage-sensitive and leak potassium conductances) and a speculative one (Table 2; by adding an 407 unconfirmed chloride conductance and leak, now balanced with larger voltage-sensitive K + 408 conductances). Their differences helped us to work out how the earlier proposed hypothetical 409 homeostatic compensation through leak-or chloride channel expression ( Niven et al., 2003;410 Vähäsöyrinki et al., 2006) would change a photoreceptor's ATP consumption. ...Context 2
... here, the conservative photoreceptor membrane model (Table 1) lacked I Cl_leak and I Cl in Eqs. 3, 431 4 and 6, whereas the speculative model (Table 2) included them. But for both membrane models, 432 because we estimated LIC directly from the stochastic phototransduction model (above), we could 433 calculate a R1-R6's energy cost in response to any arbitrary light pattern, including naturalistic 434 stimulation. ...Context 3
... 1965;Laughlin et al., 1998;Skou, 1998). For these estimates, we generated 405 two separate photoreceptor membrane models: a conservative one (Table 1; containing the known 406 voltage-sensitive and leak potassium conductances) and a speculative one (Table 2; by adding an 407 unconfirmed chloride conductance and leak, now balanced with larger voltage-sensitive K + 408 conductances). Their differences helped us to work out how the earlier proposed hypothetical 409 homeostatic compensation through leak-or chloride channel expression ( Niven et al., 2003;410 Vähäsöyrinki et al., 2006) would change a photoreceptor's ATP consumption. ...Context 4
... here, the conservative photoreceptor membrane model (Table 1) lacked I Cl_leak and I Cl in Eqs. 3, 431 4 and 6, whereas the speculative model (Table 2) included them. But for both membrane models, 432 because we estimated LIC directly from the stochastic phototransduction model (above), we could 433 calculate a R1-R6's energy cost in response to any arbitrary light pattern, including naturalistic 434 stimulation. ...Similar publications
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent an unlimited source of human CMs that could be a standard tool in drug research. However, there is concern whether hiPSC-CMs express all cardiac ion channels at physiological level and whether they might express non-cardiac ion channels. In a control hiPSC line, we fou...
Citations
... Ca2+-activated K+ channels (BK and SK) are ubiquitous in synaptic circuits which reduce network excitability [93]. Bidirectional control of BK and SK channel open probability by calmodulin-dependent kinase II (CAMKII) and protein kinase C (PKC) in medial vestibular nucleus neurons enables dynamic control of excitability during plasticity [50]. ...
Vestibular compensation is a physiological response of the vestibular organs within the inner ear. This adaptation manifests during consistent exposure to acceleration or deceleration, with the vestibular organs incrementally adjusting to such changes. The molecular underpinnings of vestibular compensation remain to be fully elucidated, yet emerging studies implicate associations with neuroplasticity and signal transduction pathways. Throughout the compensation process, the vestibular sensory neurons maintain signal transmission to the central equilibrium system, facilitating adaptability through alterations in synaptic transmission and neuronal excitability. Notable molecular candidates implicated in this process include variations in ion channels and neurotransmitter profiles, as well as neuronal and synaptic plasticity, metabolic processes, and electrophysiological modifications. This study consolidates the current understanding of the molecular events in vestibular compensation, augments the existing research landscape, and evaluates contemporary therapeutic strategies. Furthermore, this review posits potential avenues for future research that could enhance our comprehension of vestibular compensation mechanisms.
... S19A) must, in part, reflect the preparation quality. But it may also partly signify synaptic feedback strength (13,26,28,29,62) -top-down signaling from the brain (34), reflecting each fly's intrinsic activity state or attentiveness during the experiments. For example, dSK-mutants' intracellular R1-R6 photoreceptor voltage responses are faster and smaller than wild-type flies because they receive tonic feedback overload from visual interneurons (62,63). ...
... But it may also partly signify synaptic feedback strength (13,26,28,29,62) -top-down signaling from the brain (34), reflecting each fly's intrinsic activity state or attentiveness during the experiments. For example, dSK-mutants' intracellular R1-R6 photoreceptor voltage responses are faster and smaller than wild-type flies because they receive tonic feedback overload from visual interneurons (62,63). Correspondingly, their photoreceptor microsaccades are also faster and smaller (see Section II.8.i. and fig. ...
... Other predictable observations indicate synaptic feedback modulating R1-R7/8 microsaccades: dSK mutants' microsaccades ( fig. S27B) were faster and smaller than those of the wildtype flies, consistent with their accelerated photoreceptor voltage responses (62,63). dSK mutant R1-R6 photoreceptors have been shown to experience a tonic synaptic feedback overload from the lamina visual interneurons, which continuously depolarize them, making their voltage responses smaller and faster. ...
Neural mechanisms behind stereopsis, which requires simultaneous disparity inputs from two eyes, have remained mysterious. Here we show how ultrafast mirror-symmetric photomechanical contractions in the frontal forward-facing left and right eye photoreceptors give Drosophila super-resolution 3D-vision. By interlinking multiscale in vivo assays with multiscale simulations, we reveal how these photoreceptor microsaccades-by verging, diverging and narrowing the eyes' overlapping receptive fields-channel depth information, as phasic binocular image motion disparity signals in time. We further show how peripherally, outside stereopsis,
... S19A) must, in part, reflect the preparation quality. But it may also partly signify synaptic feedback strength (13,26,28,29,62) -top-down signaling from the brain (34), reflecting each fly's intrinsic activity state or attentiveness during the experiments. For example, dSK-mutants' intracellular R1-R6 photoreceptor voltage responses are faster and smaller than wild-type flies because they receive tonic feedback overload from visual interneurons (62,63). ...
... But it may also partly signify synaptic feedback strength (13,26,28,29,62) -top-down signaling from the brain (34), reflecting each fly's intrinsic activity state or attentiveness during the experiments. For example, dSK-mutants' intracellular R1-R6 photoreceptor voltage responses are faster and smaller than wild-type flies because they receive tonic feedback overload from visual interneurons (62,63). Correspondingly, their photoreceptor microsaccades are also faster and smaller (see Section II.8.i. and fig. ...
... Other predictable observations indicate synaptic feedback modulating R1-R7/8 microsaccades: dSK mutants' microsaccades ( fig. S27B) were faster and smaller than those of the wildtype flies, consistent with their accelerated photoreceptor voltage responses (62,63). dSK mutant R1-R6 photoreceptors have been shown to experience a tonic synaptic feedback overload from the lamina visual interneurons, which continuously depolarize them, making their voltage responses smaller and faster. ...
Neural mechanisms behind stereopsis, which requires simultaneous disparity inputs from two eyes, have remained mysterious. Here we show how ultrafast mirror-symmetric photomechanical contractions in the frontal forward-facing left and right eye photoreceptors give Drosophila super-resolution 3D-vision. By interlinking multiscale in vivo assays with multiscale simulations, we reveal how these photoreceptor microsaccades - by verging, diverging and narrowing the eyes’ overlapping receptive fields - channel depth information, as phasic binocular image motion disparity signals in time. We further show how peripherally, outside stereopsis, microsaccadic sampling tracks a forward flying fly’s optic flow field to better resolve the world in motion. These results change our understanding of how insect compound eyes work and suggest a general dynamic stereo-information sampling strategy for animals, robots and sensors.
One Sentence Summary
Drosophila use binocular mirror-symmetric photomechanical photoreceptor microsaccades to sample hyperacute depth-information.
... At the algorithmic level, they have paved the way for developing algorithms with only four sampling parameters to achieve automatic gain control and temporal adaptation . At the computational level, they have elucidated phototransduction dynamics through a framework of refractory photon information sampling, leading to a trade-off between coding efficiency and energy consumption (Li et al., 2019;Song and Juusola, 2014). We next review the multiscale "whole-cell" fly photoreceptor models, specifically focussing on the Drosophila R1-R6 photoreceptor model and its emergent properties at these levels. ...
... Whereas the later R1-R6 photoreceptor models describe how 30,000 microvilli act in parallel, transducing millions of photons into thousands of QBs and integrating them into the macroscopic "whole-cell" light-induced-current (LIC) (Song et al., 2009(Song et al., , 2012. The macroscopic LIC then charge the photoreceptor's photo-insensitive membrane, generating a macroscopic voltage response (Li et al., 2019;Niven et al., 2003;Vähäsöyrinki et al., 2006) (Fig. 1C). ...
... The model uses the Gillespie algorithm (Gillespie, 1976), a discrete and stochastic method that explicitly simulates a system with few reactants. This module transduces LIC into voltage response by reproducing the voltage-gated K + conductance dynamics on the photon-insensitive membrane (Li et al., 2019;Niven et al., 2003). ...
Understanding a neuron’s input-output relationship is a longstanding challenge. Arguably, these signalling dynamics can be better understood if studied at three levels of analysis: computational, algorithmic and implementational (Marr, 1982). But it is difficult to integrate such analyses into a single platform that can realistically simulate neural information processing. Multiscale dynamical “whole-cell” modelling, a recent systems biology approach, makes this possible. Dynamical “whole-cell” models are computational models that aim to account for the integrated function of numerous genes or molecules to behave like virtual cells in silico. However, because constructing such models is laborious, only a couple of examples have emerged since the first one, built for Mycoplasma genitalium bacterium, was reported in 2012. Here, we review dynamic “whole-cell” neuron models for fly photoreceptors and how these have been used to study neural information processing. Specifically, we review how the models have helped uncover the mechanisms and evolutionary rules of quantal light information sampling and integration, which underlie light adaptation and further improve our understanding of insect vision.
... More than 70% of cortical energy costs are directly used for neural signal processing within cortical circuits at the subcellular level, such as for opening and closing ionic channels to regulate APs and for neurotransmitter release [51]. A recent study used electrophysical and behavioral assays and biophysical modeling to show that losing Ca 2+ -activated K + channels makes communication between photoreceptors and LMCs inefficient, consuming more energy and distorting visual information flow to the brain [52]. ...
Spike-frequency adaptation, which reduces the firing rate of a neuron during a constant stimulus, is a prominent property observed in many neurons. In this work, we studied the effects of the \(I_{\mathrm{AHP}}\) spiking adaptation on the information transmission and efficiency of the Morris–Lecar (ML) neuron model in the spike-timing coding scheme. We showed that this kind of adaptation caused non-trivial spiking dynamics when the input rate was high. Under the stimulation of high-rate inputs, although \(I_{\mathrm{AHP}}\) adaptation neurons could not outperform non-adaptation neurons in terms of information rate, \(I_{\mathrm{AHP}}\) adaptation neurons yielded higher coding efficiency than non-adaptation neurons. We also found that the noise could enlarge the range of input rates that the adaptation takes effect to enhance coding efficiency. Increasing the calcium-activated \(\hbox {K}^{+}\) current could also extend the range of input rates in which adaptation takes effect. Therefore, we argue that the \(I_{\mathrm{AHP}}\) adaptation mechanism may play a role of adaptive noise cancelation mechanism in neuronal information processing, i.e., it maintains information transmission when neurons receive low-rate inputs but substantially enhancing coding efficiency for high-rate inputs and highly noise environments by suppressing the spike train variability caused by the noise.
... sympathetic neurons of the bull-frog (Akaike and Sadoshima, 1989;Marrion and Adams, 1992), neurons of dorsal motor nucleus of the vagus of guinea-pig (Sah and McLachlan, 1991), and hippocampal CA1 pyramidal neurons of the rat (Uneyama et al., 1993;Garaschuk et al., 1997). Physiological induction of Ca 2+ -activated K + currents, e.g. by membrane depolarization followed by Ca 2+ influx, leads to a reduction in the frequency of action potential firing (Stocker, 2004;Salkoff et al., 2006;Matschke et al., 2018) and in network excitability (Li et al., 2019). ...
The locus coeruleus (LC) is a nucleus within the brainstem that consists of norepinephrine-releasing neurons. It is involved in broad processes including autonomic regulation, and cognitive and emotional functions such as arousal, attention and anxiety. Understanding the mechanisms that control the excitability of LC neurons is important because they innervate widespread regions of the central nervous system. One of the key regulators is the cytosolic calcium concentration ([Ca2+]c), the increases in which can be amplified by calcium-induced calcium release (CICR) from the intracellular calcium stores. Although the electrical activities of LC neurons are regulated by changes in [Ca2+]c, the extent of CICR involvement in this regulation has remained unclear. Here we show that CICR hyperpolarizes acutely dissociated LC neurons of the rat brain and demonstrate the pathway whereby it does this. When CICR was activated by extracellular application of 10 mM caffeine, LC neurons were hyperpolarized in the current-clamp mode of the patch-clamp recording, and the majority of neurons showed an outward current in the voltage-clamp mode. This outward current was accompanied by an increase in membrane conductance, and its reversal potential was close to the K+ equilibrium potential, indicating that it is mediated by the opening of K+ channels. The outward current was generated in the absence of extracellular calcium and was blocked when the calcium stores were inhibited by applying ryanodine. Pharmacological experiments indicated that the outward current was mediated by Ca2+-activated K+ channels of the non-small conductance type. Finally, the application of caffeine led to an increase in the [Ca2+]c in these neurons, as visualized by fluorescence microscopy. These findings delineate a mechanism whereby CICR suppresses the electrical activity of LC neurons, and indicate that it could play a dynamic role in modulating the LC-mediated noradrenergic tone in the brain.
Cooperative gating of localized ion channels ranges from fine-tuning excitation–contraction coupling in muscle cells to controlling pace-making activity in the heart. Membrane deformation resulting from muscle contraction activates stretch-activated (SA) cation channels. The subsequent Ca2+ influx activates spatially localized Ca2+-sensitive K+ channels to fine-tune spontaneous muscle contraction. To characterize endogenously expressed intermediate conductance Ca2+-activated potassium (IK) channels and assess the functional relevance of the extracellular Ca2+ source leading to IK channel activity, we performed patch-clamp techniques on cricket oviduct myocytes and recorded single-channel data. In this study, we first investigated the identification of IK channels that could be distinguished from endogenously expressed large-conductance Ca2+-activated potassium (BK) channels by adding extracellular Ba2+. The single-channel conductance of the IK channel was 62 pS, and its activity increased with increasing intracellular Ca2+ concentration but was not voltage-dependent. These results indicated that IK channels are endogenously expressed in cricket oviduct myocytes. Second, the Ca2+ influx pathway that activates the IK channel was investigated. The absence of extracellular Ca2+ or the presence of Gd3+ abolished the activity of IK channels. Finally, we investigated the proximity between SA and IK channels. The removal of extracellular Ca2+, administration of Ca2+ to the microscopic region in a pipette, and application of membrane stretching stimulation increased SA channel activity, followed by IK channel activity. Membrane stretch-induced SA and IK channel activity were positively correlated. However, the emergence of IK channel activity and its increase in response to membrane mechanical stretch was not observed without Ca2+ in the pipette. These results strongly suggest that IK channels are endogenously expressed in cricket oviduct myocytes and that IK channel activity is regulated by neighboring SA channel activity. In conclusion, functional coupling between SA and IK channels may underlie the molecular basis of spontaneous rhythmic contractions.
The visual system lowers its perceptual sensitivity to a prolonged presentation of the same visual signal. This brain plasticity, called visual adaptation, is generally attributed to the response adaptation of neurons in the visual cortex. Although well-studied in the neurons of the primary visual cortex (V1), the contribution of high-level visual cortical regions to the response adaptation of V1 neurons is unclear. In the present study, we measured the response adaptation strength of V1 neurons before and after the top-down influence of the area 21a (A21a), a higher-order visual cortex homologous to the primate V4 area, was modulated with a noninvasive tool of transcranial direct current stimulation (tDCS). Our results showed that the response adaptation of V1 neurons enhanced significantly after applying anode (a-) tDCS in A21a when compared with that before a-tDCS, whereas the response adaptation of V1 neurons weakened after cathode (c-) tDCS relative to before c-tDCS in A21a. By contrast, sham (s-) tDCS in A21a had no significant impact on the response adaptation of V1 neurons. Further analysis indicated that a-tDCS in A21a significantly increased both the initial response (IR) of V1 neurons to the first several (five) trails of visual stimulation and the plateau response (PR) to the prolonged visual stimulation; the increase in PR was lower than in IR, which caused an enhancement in response adaptation. Conversely, c-tDCS significantly decreased both IR and PR of V1 neurons; the reduction in PR was smaller than in IR, which resulted in a weakness in response adaptation. Furthermore, the tDCS-induced changes of V1 neurons in response and response adaptation could recover after tDCS effect vanished, but did not occur after the neuronal activity in A21a was silenced by electrolytic lesions. These results suggest that the top-down influence of A21a may alter the response adaptation of V1 neurons through activation of local inhibitory circuitry, which enhances network inhibition in the V1 area upon an increased top-down input, weakens inhibition upon a decreased top-down input, and thus maintains homeostasis of V1 neurons in response to the long-presenting visual signals.
The locus coeruleus (LC) is a nucleus within the brainstem that consists of norepinephrine-releasing neurons. It is involved in broad processes including cognitive and emotional functions. Understanding the mechanisms that control the excitability of LC neurons is important because they innervate widespread brain regions. One of the key regulators is cytosolic calcium concentration ([Ca2+]c), the increases in which can be amplified by calcium-induced calcium release (CICR) from intracellular calcium stores. Although the electrical activities of LC neurons are regulated by changes in [Ca2+]c, the extent of CICR involvement in this regulation has remained unclear. Here we show that CICR hyperpolarizes acutely dissociated LC neurons of the rat and demonstrate the underlying pathway. When CICR was activated by extracellular application of 10 mM caffeine, LC neurons were hyperpolarized in the current-clamp mode of patch-clamp recording, and the majority of neurons showed an outward current in the voltage-clamp mode. This outward current was accompanied by increased membrane conductance, and its reversal potential was close to the K+ equilibrium potential, indicating that it is mediated by opening of K+ channels. The outward current was generated in the absence of extracellular calcium and was blocked when the calcium stores were inhibited by applying ryanodine. Pharmacological blockers indicated that it was mediated by Ca2+-activated K+ channels of the non-small conductance type. The application of caffeine increased [Ca2+]c, as visualized by fluorescence microscopy. These findings show CICR suppresses LC neuronal activity, and indicate its dynamic role in modulating the LC-mediated noradrenergic tone in the brain.
