Biology subjects

Joselevitch, C.

Publications and source records attributed to Joselevitch, C..

3 recordsLinked to original sources

bioRxiv2020

VOLTAGE-GATED POTASSIUM CHANNELS CONTROL THE GAIN OF ROD-DRIVEN LIGHT RESPONSES IN MIXED-INPUT ON BIPOLAR CELLS

To achieve high sensitivity at scotopic levels, vision sacrifices spatial and temporal resolution. The detection of dim light, however, depends crucially on the ability of the visual system to speed up rod signals as they advance towards the brain. At higher light levels, gain control mechanisms are necessary to prevent premature saturation of second-order neurons. We investigated how goldfish mixed-input ON bipolar cells (ON mBCs) manage to partially compensate for the intrinsically slow kinetics of rod signals in the dark-adapted state, and at the same time control the gain of rod signals. Rod-driven responses of axotomized ON mBCs become faster and more transient than those of rod horizontal cells as stimulus intensity increases. This transientness has a voltage-dependency consistent with the activation of a voltage-gated K+ conductance. Simulations with NEURON indicate that the voltage-gated K+ channels responsible for speeding up responses are concentrated at the distal tips of the bipolar cell dendrites, close to the glutamate receptors. These channels act as a gain control mechanism, by shunting the effect of tonically hyperpolarized rods onto the ON mBC. Further activation of K+ channels accelerates the ON mBC response by decreasing the membrane time constant as light levels increase. Therefore, the presence of voltage-gated K+ channels at the dendritic tips of ON mBCs extends the dynamic range of these neurons, and at the same time generates a transient signal already at the first visual synapse. Key Points SummaryO_LIHere we show that voltage-gated potassium channels can adjust the gain of the rod input to mixed-input ON bipolar cells and generate a transient signal already at the first visual synapse. C_LIO_LIThese channels are activated during the light-induced depolarization, making bipolar cell light responses smaller, faster, and more transient, effects that can be abolished by the K+ channel blocker TEA. C_LIO_LIMathematical simulations suggest that these channels are concentrated at the bipolar cell dendritic tips, close to the site of rod input. C_LIO_LIThis kind of gain control happens at all levels in the retina and is especially important for cells that receive mixed input from rods and cones, in order to prevent premature saturation with increasing light levels and remove the temporal redundancy of the photoreceptor signal. C_LI

neuroscience↗

bioRxiv2020

Expression and distribution of synaptotagmin isoforms in the zebrafish retina

Synaptotagmins belong to a large family of proteins. While various synaptotagmins have been implicated as Ca2+ sensors for vesicle replenishment and release at conventional synapses, their roles at retinal ribbon synapses remain incompletely understood. Zebrafish is a widely used experimental model for retinal research. We therefore investigated the homology between human, rat, mouse, and zebrafish synaptotagmins 1 to 10 using a bioinformatics approach. We also characterized the expression and distribution of various synaptotagmin (syt) genes in the zebrafish retina, using RT-PCR and in situ hybridization, focusing on the family members whose products likely underlie Ca2+-dependent exocytosis in the central nervous system (synaptotagmins 1, 2, 5 and 7). We find that most zebrafish synaptotagmins are well conserved and can be grouped in the same classes as mammalian synaptotagmins, based on crucial amino acid residues needed for coordinating Ca2+ binding and determining phospholipid binding affinity. The only exception is synaptotagmin 1b, which lacks 34 amino acid residues in the C2B domain and is therefore unlikely to bind Ca2+ there. Additionally, the products of zebrafish syt5a and syt5b genes share identity with mammalian class 1 and class 5 synaptotagmins. Zebrafish syt1, syt2, syt5 and syt7 paralogues are found in the zebrafish brain, eye, and retina, excepting syt1b, which is only present in the brain. The complementary expression pattern of the remaining paralogues in the retina suggests that syt1a and syt5a may underlie synchronous release and syt7a and syt7b may mediate asynchronous release or other Ca2+ dependent processes in different types of retinal neurons.

neuroscience↗

bioRxiv2020

Direct Observation Of Vesicle Transport On The Synaptic Ribbon Provides Evidence That Vesicles Are Mobilized And Prepared Rapidly For Release

Synaptic ribbons are thought to provide vesicles for continuous synaptic transmission in some retinal non-spiking neurons, yet recent studies indicate that genetic removal of the ribbon has little effect on vesicle release kinetics. To investigate vesicle replenishment at synaptic ribbons, we imaged synaptic vesicles and ribbons in retinal bipolar cells with TIRF microscopy during stimulation with trains of 30-ms depolarizations. Analysis of vesicles released by the stimuli revealed that the vast majority of releasable vesicles reside within 300 nm of the ribbon center. A single 30-ms step to 0 mV was sufficient to deplete the most membrane-proximal vesicle pool, while triggering rapid stepwise movements of distal vesicles along the ribbon and toward the plasma membrane. Replenishment only becomes rate-limiting for recovery from paired-pulse depression for interstimulus intervals shorter than 250 ms. For longer interstimulus intervals, vesicle movement down the ribbon is fast enough to replenish released vesicles, but newly arrived vesicles are not release-ready. Notably, vesicle re-supply is 40-to 50-fold faster than previously measured in non-ribbon conventional synapses, whereas vesicle maturation rate is comparable. Moreover, in contrast to conventional synapses, vesicles docked at the base of the ribbon release with high fidelity. Lastly, our data show that with multiple stimuli, the delay in vesicle departure increases. Our results support a role for ribbons in the rapid supply and efficient preparation of vesicles for release, provide direct measurements of vesicle movement down the synaptic ribbon and suggest that multiple factors contribute to paired-pulse depression.

neuroscience↗