Biomedical subjects

M Juusola

Publications and source records attributed to M Juusola.

At least 19 recordsLinked to original sources

PubMed2003

Shaker K(+)-channels are predicted to reduce the metabolic cost of neural information in Drosophila photoreceptors.

Shaker K(+)-channels are one of several voltage-activated K(+)-channels expressed in Drosophila photoreceptors. We have shown recently that Shaker channels act as selective amplifiers, attenuating some signals while boosting others. Loss of these channels reduces the photoreceptor information capacity (bits s(-1)) and induces compensatory changes in photoreceptors enabling them to minimize the impact of this loss upon coding natural-like stimuli. Energy as well as coding is also an important consideration in understanding the role of ion channels in neural processing. Here, we use a simple circuit model that incorporates the major ion channels, pumps and exchangers of the photoreceptors to derive experimentally based estimates of the metabolic cost of neural information in wild-type (WT) and Shaker mutant photoreceptors. We show that in WT photoreceptors, which contain Shaker K(+)-channels, each bit of information costs approximately half the number of ATP molecules than each bit in Shaker photoreceptors, in which lack of the Shaker K(+)-channels is compensated by increased leak conductance. Additionally, using a Hodgkin-Huxley-type model coupled to the circuit model we show that the amount of leak present in both WT and Shaker photoreceptors is optimized to both maximize the available voltage range and minimize the metabolic cost.

Adenosine Triphosphate↗

PubMed2002

Molecular basis of amplification in Drosophila phototransduction: roles for G protein, phospholipase C, and diacylglycerol kinase.

In Drosophila photoreceptors, the amplification responsible for generating quantum bumps in response to photoisomerization of single rhodopsin molecules has been thought to be mediated downstream of phospholipase C (PLC), since bump amplitudes were reportedly unaffected in mutants with greatly reduced levels of either G protein or PLC. We now find that quantum bumps in such mutants are reduced approximately 3- to 5-fold but are restored to near wild-type values by mutations in the rdgA gene encoding diacylglycerol kinase (DGK) and also by depleting intracellular ATP. The results demonstrate that amplification requires activation of multiple G protein and PLC molecules, identify DGK as a key enzyme regulating amplification, and implicate diacylglycerol as a messenger of excitation in Drosophila phototransduction.

Adenosine Triphosphate↗

PubMed2001

Calcium influx via TRP channels is required to maintain PIP2 levels in Drosophila photoreceptors.

The trp (transient receptor potential) gene encodes a Ca2+ channel responsible for the major component of the phospholipase C (PLC) mediated light response in Drosophila. In trp mutants, maintained light leads to response decay and temporary total loss of sensitivity (inactivation). Using genetically targeted PIP2-sensitive inward rectifier channels (Kir2.1) as biosensors, we provide evidence that trp decay reflects depletion of PIP2. Two independent mutations in the PIP2 recycling pathway (rdgB and cds) prevented recovery from inactivation. Abolishing Ca2+ influx in wild-type photoreceptors mimicked inactivation, while raising Ca2+ by blocking Na+/Ca2+ exchange prevented inactivation in trp. The results suggest that Ca2+ influx prevents PIP2 depletion by inhibiting PLC activity and facilitating PIP2 recycling. Without this feedback one photon appears sufficient to deplete the phosphoinositide pool of approximately 4 microvilli.

Animals↗

PubMed2001

Light adaptation in Drosophila photoreceptors: II. Rising temperature increases the bandwidth of reliable signaling.

It is known that an increase in both the mean light intensity and temperature can speed up photoreceptor signals, but it is not known whether a simultaneous increase of these physical factors enhances information capacity or leads to coding errors. We studied the voltage responses of light-adapted Drosophila photoreceptors in vivo from 15 to 30 degrees C, and found that an increase in temperature accelerated both the phototransduction cascade and photoreceptor membrane dynamics, broadening the bandwidth of reliable signaling with an effective Q(10) for information capacity of 6.5. The increased fidelity and reliability of the voltage responses was a result of four factors: (1) an increased rate of elementary response, i.e., quantum bump production; (2) a temperature-dependent acceleration of the early phototransduction reactions causing a quicker and narrower dispersion of bump latencies; (3) a relatively temperature-insensitive light-adapted bump waveform; and (4) a decrease in the time constant of the light-adapted photoreceptor membrane, whose filtering matched the dynamic properties of the phototransduction noise. Because faster neural processing allows faster behavioral responses, this improved performance of Drosophila photoreceptors suggests that a suitably high body temperature offers significant advantages in visual performance.

Adaptation, Physiological↗

PubMed2001

Light adaptation in Drosophila photoreceptors: I. Response dynamics and signaling efficiency at 25 degrees C.

Besides the physical limits imposed on photon absorption, the coprocessing of visual information by the phototransduction cascade and photoreceptor membrane determines the fidelity of photoreceptor signaling. We investigated the response dynamics and signaling efficiency of Drosophila photoreceptors to natural-like fluctuating light contrast stimulation and intracellular current injection when the cells were adapted over a 4-log unit light intensity range at 25 degrees C. This dual stimulation allowed us to characterize how an increase in the mean light intensity causes the phototransduction cascade and photoreceptor membrane to produce larger, faster and increasingly accurate voltage responses to a given contrast. Using signal and noise analysis, this appears to be associated with an increased summation of smaller and faster elementary responses (i.e., bumps), whose latency distribution stays relatively unchanged at different mean light intensity levels. As the phototransduction cascade increases, the size and speed of the signals (light current) at higher adapting backgrounds and, in conjunction with the photoreceptor membrane, reduces the light-induced voltage noise, and the photoreceptor signal-to-noise ratio improves and extends to a higher bandwidth. Because the voltage responses to light contrasts are much slower than those evoked by current injection, the photoreceptor membrane does not limit the speed of the phototransduction cascade, but it does filter the associated high frequency noise. The photoreceptor information capacity increases with light adaptation and starts to saturate at approximately 200 bits/s as the speed of the chemical reactions inside a fixed number of transduction units, possibly microvilli, is approaching its maximum.

Adaptation, Physiological↗

PubMed1998

Adaptation properties of two types of sensory neurons in a spider mechanoreceptor organ.

The VS-3 slit-sense organs of the tropical wandering spider Cupiennius salei contain two types of mechanosensory neurons with similar morphology but different adaptation properties. We measured the changes in membrane potential produced by mechanical stimulation and by electric current stimulation in a large number of neurons of both types. No significant differences were found between the passive membrane properties of the two groups, but there were significant differences in the extent and time course of receptor potential adaptation between the two types of neurons. These data, combined with the responses to suprathreshold electrical stimuli, indicate that adaptational differences exist at several stages in these neurons but that active membrane conductances dominate the overall behavior. The passive membrane measurements also indicate that effective voltage clamp of the receptor current at the tips of the sensory dendrites is possible in these neurons.

Action Potentials↗

PubMed1997

Rapid coating of glass-capillary microelectrodes for single-electrode voltage-clamp.

The single-electrode voltage-clamp technique requires sharp glass-capillary microelectrodes, whose electrical properties often limit the capabilities of the recording system. Here, we describe a rapid and simple way of coating fine microelectrodes with Dricote and Vaseline that improves their performance during voltage-clamp. The coating prevented clogging of the tips, improved the capacitance compensation of the electrodes, helped to seal the electrode tips into cell membranes and allowed visualization of the tips under saline solution. This new coating method led to greatly improved recordings and better characterization of the transduction and voltage-activated currents in an isolated preparation of spider mechanosensory neurons.

Animals↗

PubMed1997

The efficiency of sensory information coding by mechanoreceptor neurons.

Most sensory systems encode external signals into action potentials for transmission to the central nervous system, but little is known about the cost or efficiency of this encoding. We measured the information capacity at three stages of encoding in the neurons of a spider slit-sense mechanoreceptor organ. For the receptor current under voltage clamp, the capacity was approximately 1400 bits/s, but when the neuron was allowed to generate a receptor potential, nonlinear membrane processes improved the capacity to >2000 bits/s. Finally, when action potentials were produced, the capacity dropped to approximately 200 bits/s, or approximately 14% of the receptor current capacity. These measurements provide a quantitative estimation of the cost of encoding analog signals into action potentials.

Action Potentials↗

PubMed1997

Visual acuity for moving objects in first- and second-order neurons of the fly compound eye.

The early stages of visual systems contain a variety of components that limit both the spatial resolution and the temporal resolution of vision. When an animal sees a moving object, or moves relative to its environment, both spatial and temporal factors contribute to its ability to resolve the movement. In the present work we have combined currently available knowledge about the early stages of fly vision (optical system, photoreceptors, and large monopolar cells) to predict the resolution of the first two cell layers to moving point objects. These calculations included recent measurements of nonlinear light responses. Because background light level has a strong effect on the temporal behavior of these early visual layers, we examined the effects of light level on motion resolution. We also studied the effect of position within the eye, which is known to affect the static resolution of vision. Our results indicate that responses in large monopolar cells to moving point objects are maximal at angular velocities of 100-200 degrees/s. The resolution of point objects by both these early stages of the visual system is similar from stationary to an angular velocity of approximately 200 degrees/s. Above this, resolution deteriorates approximately linearly with velocity.

Animals↗

PubMed1996

Information processing by graded-potential transmission through tonically active synapses.

Many neurons use graded membrane-potential changes, instead of action potentials, to transmit information. Traditional synaptic models feature discontinuous transmitter release by presynaptic action potentials, but this is not true for synapses between graded-potential neurons. In addition to graded and continuous transmitter release, they have multiple active zones, ribbon formations and L-type Ca2+ channels. These differences are probably linked to the high rate of vesicle fusion required for continuous transmitter release. Early stages of sensory systems provide some of the best characterized graded-potential neurons, and recent work on these systems suggests that modification of synaptic transmission by adaptation is a powerful feature of graded synapses.

Animals↗

PubMed1995

Recording from cuticular mechanoreceptors during mechanical stimulation.

It is technically demanding to make intracellular measurements of mechanoreception in intact arthropod cuticular receptors. Here we introduce a method for recording mechanically induced electrical events in a class of spider mechanoreceptors using single electrode voltage- or current-clamp. A concave piece of cuticle containing a mechanosensitive lyriform slit organ was dissected free and fixed with wax onto a specially designed holder. This holder-cuticle complex, filled with spider saline, allowed displacement of the slit membrane from below while simultaneously recording intracellularly from neurons of the organ through a thin saline film. Extracellular ion concentrations could be changed and ion channel blockers could be applied to the bath. The method promises to allow the investigation of the ion channels responsible for mechanically transduced receptor signals and spike encoding.

Animals↗

PubMed1995

Transfer of graded potentials at the photoreceptor-interneuron synapse.

To characterize the transfer of graded potentials and the properties of the associated noise in the photoreceptor-interneuron synapse of the blowfly (Calliphora vicina) compound eye, we recorded voltage responses of photoreceptors (R1-6) and large monopolar cells (LMC) evoked by: (a) steps of light presented in the dark; (b) contrast steps; and (c) pseudorandomly modulated contrast stimuli at backgrounds covering 6 log intensity units. Additionally, we made recordings from photoreceptor axon terminals. Increased light adaptation gradually changed the synaptic signal transfer from low-pass to band-pass filtering. This was accompanied by decreased synaptic delay and increased contrast gain, but the overall synaptic gain and the intrinsic noise (i.e., transmission noise) were reduced. Based on these results, we describe a descriptive synaptic model, in which the kinetics of the tonic transmitter (histamine) release from the photoreceptor axon terminals change with mean photoreceptor depolarization. During signal transmission, tonic transmitter release is augmented by voltage-dependent contrast-enhancing mechanisms in the photoreceptor axons that produce fast transients from the rising phases of the photoreceptor responses and add these enhanced voltages to the original photoreceptor responses. The model can predict the experimental findings and it agrees with the recently proposed theory of maximizing sensory information.

Animals↗

PubMed1995

Graded responses and spiking properties of identified first-order visual interneurons of the fly compound eye.

1. We studied the graded and spiking properties of the "non-spiking" first-order visual interneurons of the fly compound eye in situ with the use of intracellular recordings. Iontophoretical QX-314 injections, Lucifer yellow marking, and (discontinuous) current-clamp method together with transfer function analysis were used to characterize the neural signal processing mechanisms in these neurons. 2. A light-OFF spike was seen in one identified anatomic subtype (L3, n = 6) of the three first-order visual interneurons (L1, L2, and L3, or LMCs) when recorded from synaptic region (i.e., in the 1st visual ganglion, lamina ganglionaris) in dark-adapted conditions. Hyperpolarization of the membrane potential by current caused the identified L1 (n = 4), as well as L3 (n = 6), to produce an OFF spike, a number of action potentials, and some subthreshold depolarizations after the light-ON response. In L2 the OFF spike or action potentials could not be elicited. 3. To produce action potentials in L1 and L3, it was found to be necessary to hyperpolarize the cells approximately 35-45 mV (n = 43) below the resting potential (RP) in the synaptic zone. Recordings from the axons of these cells revealed that near the second neuropil (chiasma) the threshold of these spikes was near to (approximately 10 mV below, n = 16) or even at the RP when an ON spike was also produced (n = 4). 4. The recorded spikes were up to 54 mV in amplitude, appeared with a maximum frequency of up to 120 impulses/s, and had a duration of approximately 8 ms. In L1 and L3 the spikes were elicited either after a light pulse (L3) or after a negative current step that was superimposed on a hyperpolarizing steady-state current (L3 and L1). A positive current step (similarly superimposed on a hyperpolarizing steady-state current) also triggered the spikes during the step. 5. Iontophoretic injection of a potent intracellularly effective blocker of voltage-gated sodium channels, QX-314, irreversibly eradicated the spikes and subthreshold depolarizations (n = 5). In addition, further injections elongated the light-ON responses and decreased or even abolished the light-OFF response. 6. Negative prepulses followed by positive current steps were applied from the RP, to test the activation-inactivation properties of the channels responsible for the OFF spike.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1995

Tonic transmitter release in a graded potential synapse.

1. We studied graded synaptic transmission in the fly photoreceptor-interneuron synapse by using intracellular in situ recordings from pre- and postsynaptic cells. 2. A large presynaptic hyperpolarization after light adaptation, caused by the activation of the electrogenic Na+/K+ pump, drastically reduced the conspicuous postsynaptic dark noise. At the same time, the postsynaptic neurons depolarized, with an increase of input resistance of 5-10 M omega. 3. The spectral characteristics of the postsynaptic membrane noise in dark and during noise reduction, together with the other results, suggested that the transmitter release decreased dramatically approximately 12 mV below the resting potential of the presynaptic photoreceptors. 4. During the postsynaptic noise reduction, the saturated and subsaturated first-order visual interneuron responses were increased up to 9 mV with a time constant of recovery of approximately 10 s. This increase was shown to be caused by the negative shift of the reversal potential of the transmitter-gated (mainly Cl-) conductance, caused apparently by the reduced transmitter input. 5. The results strongly suggest that the photoreceptor transmitter release in fly is tonic, even in dark, and further support the modulation of the synaptic voltage transfer by postsynaptic Cl- extrusion.

Animals↗

PubMed1995

Transduction and adaptation in spider slit sense organ mechanoreceptors.

1. Mechanoreceptor neurons in spider (Cupiennlus salei) slit sense organ were examined by intracellular current- and voltageclarry recordings. Steps and pseudorandomly modulated displacement stimuli were delivered to the mechanosensitive cuticular slits. The resulting responses were used to determine the response dynamics and signal-to-noise ratio (SNR) of mechanoelectrical transduction. 2. Neurons were separated into two groups that, in terms of their afferent discharges, displayed different adaptations to displacement stimuli. Both responded at the onset of the step but then adapted fully, either immediately or within 10-200 ms. Voltage-clamp recordings showed only small differences in the receptor currents of the two groups. 3. Displacement of the slit caused a large inward current that decayed in seconds to a steady level of approximately 10-25% of the initial transient. When adapted to a steady displacement, the neurons responded to superimposed displacements in the same direction with additional transient currents, whose decay could be fitted by two exponentials with time constants of approximately 10 and 100 ms. In contrast, displacement in the opposite direction caused small "outward" currents without obvious adaptation. This behavior persisted with increasing background displacements, suggesting a shift in the displacement-response curve along the displacement axis. 4. White noise stimulation supported the step data and confirmed that the receptor's sensitivity was independent of mean slit membrane displacement. When the relative displacement of the stimulus (i.e., strain) was held constant at different maintained backgrounds, the SNR of the neurons remained fairly constant at approximately 2-10 over the frequency range from 4 to 450 Hz. The receptor current frequency responses showed high-pass characteristics, with a two- to sevenfold enhancement of the response amplitude and a phase lag relative to the stimulus of 90 degrees at 300 Hz. Low coherence values in the frequency range of 0.5-125 Hz were explained by nonlinear adaptation. 5. We conclude that, by rapidly adapting to the mean displacement of the slit membrane, slit organ mechanoreceptor neurons maintain a high sensitivity and SNR that allow the detection of small and rapid changes in cuticular strain.

Acoustic Stimulation↗

PubMed1995

Nonlinear models of the first synapse in the light-adapted fly retina.

1. Randomly modulated light stimuli were used to characterize the nonlinear dynamic properties of the synapse between photoreceptors and large monopolar neurons (LMC) in the fly retina. Membrane potential fluctuations produced by constant variance contrast stimuli were recorded at eight different levels of background light intensity. 2. Representation of the photoreceptor-LMC input-output data in the form of traditional characteristic curves indicated that synaptic gain was reduced by light adaptation. However, this representation did not include the time-dependent properties of the synaptic function, which are known to be nonlinear. Therefore nonlinear systems analysis was used to characterize the synapse. 3. The responses of photoreceptors and LMCs to random light fluctuations were characterized by second-order Volterra series, with kernel estimation by the parallel cascade method. Photoreceptor responses were approximately linear, but LMC responses were clearly nonlinear. 4. Synaptic input-output relationships were measured by passing the light stimuli to LMCs through the measured photoreceptor characteristics to obtain an estimate of the synaptic input. The resulting nonlinear synaptic functions were well characterized by second-order Volterra series. They could not be modeled by a linear-nonlinear-linear cascade but were better approximated by a nonlinear-linear-nonlinear cascade. 5. These results support two possible structural models of the synapse, the first having two parallel paths for signal flow between the photoreceptor and LMC, and the second having two distinct nonlinear operations, occurring before and after chemical transmission. 6. The two models were cach used to calculate the synaptic gain to a brief change in photoreceptor membrane potential. Both models predicted that synaptic gain is reduced by light adaptation.

Adaptation, Ocular↗

PubMed1994

Measuring complex admittance and receptor current by single electrode voltage-clamp.

Studying the membrane properties of small excitable cells like sensory receptors in situ is often difficult. Two new techniques are described here which utilize white noise during single-electrode voltage-clamp. Cells are impaled with a single microelectrode and voltage-clamped to a given holding potential, using a time-sharing technique. The first method, based on modulating the voltage command with repeated sequences of a pseudorandom stimuli, allows measurements of cell conductance (complex admittance) in the frequency domain. The second method is designed to characterize the dynamics of the receptor current in the frequency domain. In both cases, R1-6 type blowfly photoreceptors were used as experimental models. The photoreceptor was first light-adapted to a steady light background and then clamped to the resulting potential. A pseudorandomly modulated light stimulus was then superimposed on the steady light background and the resulting receptor current was recorded. The frequency response was then calculated from the light modulation and the receptor current via fast Fourier transform (FFT). By using intracellularly applied ion channel blockers, the effects of active and passive membrane properties in modulating the transmitted signals could also be studied.

Animals↗

PubMed1994

Contrast gain, signal-to-noise ratio, and linearity in light-adapted blowfly photoreceptors.

Response properties of short-type (R1-6) photoreceptors of the blowfly (Calliphora vicina) were investigated with intracellular recordings using repeated sequences of pseudorandomly modulated light contrast stimuli at adapting backgrounds covering 5 log intensity units. The resulting voltage responses were used to determine the effects of adaptational regulation on signal-to-noise ratios (SNR), signal induced noise, contrast gain, linearity and the dead time in phototransduction. In light adaptation the SNR of the photoreceptors improved more than 100-fold due to (a) increased photoreceptor voltage responses to a contrast stimulus and (b) reduction of voltage noise at high intensity backgrounds. In the frequency domain the SNR was attenuated in low frequencies with an increase in the middle and high frequency ranges. A pseudorandom contrast stimulus by itself did not produce any additional noise. The contrast gain of the photoreceptor frequency responses increased with mean illumination and the gain was best fitted with a model consisting of two second order and one double pole of first order. The coherence function (a normalized measure of linearity and SNR) of the frequency responses demonstrated that the photoreceptors responded linearly (from 1 to 150 Hz) to the contrast stimuli even under fairly dim conditions. The theoretically derived and the recorded phase functions were used to calculate phototransduction dead time, which decreased in light adaptation from approximately 5-2.5 ms. This analysis suggests that the ability of fly photoreceptors to maintain linear performance under dynamic stimulation conditions results from the high early gain followed by delayed compressive feed-back mechanisms.

Adaptation, Ocular↗