Biomedical subjects

Mikko Juusola

Publications and source records attributed to Mikko Juusola.

11 recordsLinked to original sources

PubMed2007

Coding with spike shapes and graded potentials in cortical networks.

In cortical neurones, analogue dendritic potentials are thought to be encoded into patterns of digital spikes. According to this view, neuronal codes and computations are based on the temporal patterns of spikes: spike times, bursts or spike rates. Recently, we proposed an 'action potential waveform code' for cortical pyramidal neurones in which the spike shape carries information. Broader somatic action potentials are reliably produced in response to higher conductance input, allowing for four times more information transfer than spike times alone. This information is preserved during synaptic integration in a single neurone, as back-propagating action potentials of diverse shapes differentially shunt incoming postsynaptic potentials and so participate in the next round of spike generation. An open question has been whether the information in action potential waveforms can also survive axonal conduction and directly influence synaptic transmission to neighbouring neurones. Several new findings have now brought new light to this subject, showing cortical information processing that transcends the classical models.

Action Potentials↗

PubMed2006

Normal mitochondrial dynamics requires rhomboid-7 and affects Drosophila lifespan and neuronal function.

In addition to being energy generators, mitochondria control many cellular processes including apoptosis. They are dynamic organelles, and the machinery of membrane fusion and fission is emerging as a key regulator of mitochondrial biology. We have recently identified a novel and conserved mitochondrial rhomboid intramembrane protease that controls membrane fusion in Saccharomyces cerevisiae by processing the dynamin-like GTPase, Mgm1, thereby releasing it from the membrane. The genetics of mitochondrial membrane dynamics has until now focused primarily on yeast. Here we show that in Drosophila, the mitochondrial rhomboid (Rhomboid-7) is required for mitochondrial fusion during fly spermatogenesis and muscle maturation, both tissues with unusual mitochondrial dynamics. We also find that mutations in Drosophila optic atrophy 1-like (Opa1-like), the ortholog of yeast mgm1, display similar phenotypes, suggesting a shared role for Rhomboid-7 and Opa1-like, as with their yeast orthologs. Loss of human OPA1 leads to dominant optic atrophy, a mitochondrial disease leading to childhood onset blindness. rhomboid-7 mutant flies have severe neurological defects, evidenced by compromised signaling across the first visual synapse, as well as light-induced neurodegeneration of photoreceptors that resembles the human disease. rhomboid-7 mutant flies also have a greatly reduced lifespan.

Animals↗

PubMed2006

Robustness of neural coding in Drosophila photoreceptors in the absence of slow delayed rectifier K+ channels.

Determining the contribution of a single type of ion channel to information processing within a neuron requires not only knowledge of the properties of the channel but also understanding of its function within a complex system. We studied the contribution of slow delayed rectifier K+ channels to neural coding in Drosophila photoreceptors by combining genetic and electrophysiological approaches with biophysical modeling. We show that the Shab gene encodes the slow delayed rectifier K+ channel and identify a novel voltage-gated K+ conductance. Analysis of the in vivo recorded voltage responses together with their computer-simulated counterparts demonstrates that Shab channels in Drosophila photoreceptors attenuate the light-induced depolarization and prevent response saturation in bright light. We also show that reduction of the Shab conductance in mutant photoreceptors is accompanied by a proportional drop in their input resistance. This reduction in input resistance partially restores the signaling range, sensitivity, and dynamic coding of light intensities of Shab photoreceptors to those of the wild-type counterparts. However, loss of the Shab channels may affect both the energy efficiency of coding and the processing of natural stimuli. Our results highlight the role of different types of voltage-gated K+ channels in the performance of the photoreceptors and provide insight into functional robustness against the perturbation of specific ion channel composition.

Action Potentials↗

PubMed2006

Feedback network controls photoreceptor output at the layer of first visual synapses in Drosophila.

At the layer of first visual synapses, information from photoreceptors is processed and transmitted towards the brain. In fly compound eye, output from photoreceptors (R1-R6) that share the same visual field is pooled and transmitted via histaminergic synapses to two classes of interneuron, large monopolar cells (LMCs) and amacrine cells (ACs). The interneurons also feed back to photoreceptor terminals via numerous ligand-gated synapses, yet the significance of these connections has remained a mystery. We investigated the role of feedback synapses by comparing intracellular responses of photoreceptors and LMCs in wild-type Drosophila and in synaptic mutants, to light and current pulses and to naturalistic light stimuli. The recordings were further subjected to rigorous statistical and information-theoretical analysis. We show that the feedback synapses form a negative feedback loop that controls the speed and amplitude of photoreceptor responses and hence the quality of the transmitted signals. These results highlight the benefits of feedback synapses for neural information processing, and suggest that similar coding strategies could be used in other nervous systems.

Animals↗

PubMed2005

Stimulus history reliably shapes action potential waveforms of cortical neurons.

Action potentials have been shown to shunt synaptic charge to a degree that depends on their waveform. In this way, they participate in synaptic integration, and thus in the probability of generating succeeding action potentials, in a shape-dependent way. Here we test whether the different action potential waveforms produced during dynamical stimulation in a single cortical neuron carry information about the conductance stimulus history. When pyramidal neurons in rat visual cortex were driven by a conductance stimulus that resembles natural synaptic input, somatic action potential waveforms showed a large variability that reliably signaled the history of the input for up to 50 ms before the spike. The correlation between stimulus history and action potential waveforms had low noise, resulting in information rates that were three to four times larger than for the instantaneous spike rate. The reliable correlation between stimulus history and spike waveforms then acts as a local encoding at the single-cell level. It also directly affects neuronal communication as different waveforms influence the production of succeeding spikes via differential shunting of synaptic charge. Modeling was used to show that slow conductances can implement memory of the stimulus history in cortical neurons, encoding this information in the spike shape.

Action Potentials↗

PubMed2005

Use of meixner functions in estimation of Volterra kernels of nonlinear systems with delay.

Volterra series representation of nonlinear systems is a mathematical analysis tool that has been successfully applied in many areas of biological sciences, especially in the area of modeling of hemodynamic response. In this study, we explored the possibility of using discrete time Meixner basis functions (MBFs) in estimating Volterra kernels of nonlinear systems. The problem of estimation of Volterra kernels can be formulated as a multiple regression problem and solved using least squares estimation. By expanding system kernels with some suitable basis functions, it is possible to reduce the number of parameters to be estimated and obtain better kernel estimates. Thus far, Laguerre basis functions have been widely used in this framework. However, research in signal processing indicates that when the kernels have a slow initial onset or delay, Meixner functions, which can be made to have a slow start, are more suitable in terms of providing a more accurate approximation to the kernels. We, therefore, compared the performance of Meixner functions, in kernel estimation, to that of Laguerre functions in some test cases that we constructed and in a real experimental case where we studied photoreceptor responses of photoreceptor cells of adult fruitflies (Drosophila melanogaster). Our results indicate that when there is a slow initial onset or delay, MBF expansion provides better kernel estimates.

Algorithms↗

PubMed2004

Impact of rearing conditions and short-term light exposure on signaling performance in Drosophila photoreceptors.

The amount of visual information an animal can extract from its environment is ultimately limited by the signaling performance of its photoreceptors. To maximize their performance, photoreceptors must be able to accommodate large changes in input caused by the dynamic properties of the visual environment and the animal's own behavior. This is likely to require a range of adaptation mechanisms operating over multiple time scales. Using intracellular recordings, we investigated the effects of developmental light rearing conditions and the effects of 2 h light or dark exposure prior the experiment on the signaling performance of adult Drosophila melanogaster photoreceptors. We show that light-rearing amplifies photoreceptors' voltage responses to light contrast changes by >or =20% and accelerates them by 3 ms. We argue that these differences mostly reflect changes in the timing of the early phototransduction reactions, some of which are persistent. However, being born and nurtured in certain lighting conditions does not set an ultimate limit for the signaling performance of Drosophila photoreceptors. Two-hour light exposure prior to the experiment can improve the information capacity of dark-reared photoreceptors close to the values of light-reared photoreceptors by reducing voltage noise. This effect may originate from plastic changes in the utilization of phototransduction proteins and ion channels.

Animals↗

PubMed2004

Interactions between light-induced currents, voltage-gated currents, and input signal properties in Drosophila photoreceptors.

Voltage-gated K(+) channels are important in neuronal signaling, but little is known of their interactions with receptor currents or their behavior during natural stimulation. We used nonparametric and parametric nonlinear modeling of experimental responses, combined with Hodgkin-Huxley style simulation, to examine the roles of K(+) channels in forming the responses of wild-type (WT) and Shaker mutant (Sh(14)) Drosophila photoreceptors to naturalistic stimulus sequences. Naturalistic stimuli gave results different from those of similar experiments with white noise stimuli. Sh(14) responses were larger and faster than WT. Simulation indicated that, in addition to eliminating the Shaker current, the mutation changed the current flowing through light-dependent channels [light-induced current (LIC)] and increased the delayed rectifier current. Part of the change in LIC could be attributed to direct feedback from the voltage-sensitive ion channels to the light-sensitive channels by the membrane potential. However, we argue that other changes occur in the light detecting machinery of Sh(14) mutants, possibly during photoreceptor development.

Animals↗

PubMed2003

The rate of information transfer of naturalistic stimulation by graded potentials.

We present a method to measure the rate of information transfer for any continuous signals of finite duration without assumptions. After testing the method with simulated responses, we measure the encoding performance of Calliphora photoreceptors. We find that especially for naturalistic stimulation the responses are nonlinear and noise is nonadditive, and show that adaptation mechanisms affect signal and noise differentially depending on the time scale, structure, and speed of the stimulus. Different signaling strategies for short- and long-term and dim and bright light are found for this graded system when stimulated with naturalistic light changes.

Action Potentials↗

PubMed2003

Shaker K+ channels contribute early nonlinear amplification to the light response in Drosophila photoreceptors.

We describe the contribution of rapidly inactivating Shaker K+ channels to the dynamic membrane properties of Drosophila photoreceptors. Phototransduction was measured in wild-type and Shaker mutant (Sh14) Drosophila photoreceptors by stimulating with white noise-modulated light contrast and recording the resulting intracellular membrane potential fluctuations. A second-order Volterra kernel series was used to characterize the nonlinear dynamic properties of transduction in the two situations. First-order kernels were indistinguishable in wild-type and Sh14 photoreceptors, indicating that the basic light transduction machinery was always intact. However, second-order kernels of Shaker mutants lacked a large, early amplification, indicating a novel role for Shaker K+ channels in amplifying and accelerating the voltage response of wild-type photoreceptors. A cascade model of two nonlinear static components surrounding one linear dynamic component was able to partially reproduce the experimental responses. Parameters obtained by fitting the model to the experimental data supported the hypothesis that normal Shaker K+ channels contribute an early, positive nonlinearity that partially offsets a later attenuating nonlinearity caused by membrane shunting.

Animals↗

PubMed2003

The contribution of Shaker K+ channels to the information capacity of Drosophila photoreceptors.

An array of rapidly inactivating voltage-gated K+ channels is distributed throughout the nervous systems of vertebrates and invertebrates. Although these channels are thought to regulate the excitability of neurons by attenuating voltage signals, their specific functions are often poorly understood. We studied the role of the prototypical inactivating K+ conductance, Shaker, in Drosophila photoreceptors by recording intracellularly from wild-type and Shaker mutant photoreceptors. Here we show that loss of the Shaker K+ conductance produces a marked reduction in the signal-to-noise ratio of photoreceptors, generating a 50% decrease in the information capacity of these cells in fully light-adapted conditions. By combining experiments with modelling, we show that the inactivation of Shaker K+ channels amplifies voltage signals and enables photoreceptors to use their voltage range more effectively. Loss of the Shaker conductance attenuated the voltage signal and induced a compensatory decrease in impedance. Our results demonstrate the importance of the Shaker K+ conductance for neural coding precision and as a mechanism for selectively amplifying graded signals in neurons, and highlight the effect of compensatory mechanisms on neuronal information processing.

Animals↗