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Light Adaptation in Drosophila Photoreceptors: I. Response Dynamics and Signaling Efficiency at 25ЊC

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Light Adaptation in Drosophila Photoreceptors: I. Response Dynamics and Signaling Efficiency at 25ЊC Light Adaptation in Drosophila Photoreceptors: I. Response Dynamics and Signaling Efficiency at 25ЊC Mikko Juusola* and Roger C. Hardie‡ From the *Physiological Laboratory, University of Cambridge, Cambridge CB2 3EG, United Kingdom; and ‡Department of Anatomy, University of Cambridge, Cambridge CB2 3DY, United Kingdom abstract 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 fluctu- ating light contrast stimulation and intracellular current injection when the cells were adapted over a 4-log unit light intensity range at 25ЊC. This dual stimulation allowed us to characterize how an increase in the mean light in- tensity causes the phototransduction cascade and photoreceptor membrane to produce larger, faster and increas- ingly 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 photore- ceptor 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 cas- cade, but it does filter the associated high frequency noise. The photoreceptor information capacity increases with bits/s as the speed of the chemical reactions inside a fixed number 200ف light adaptation and starts to saturate at of transduction units, possibly microvilli, is approaching its maximum. key words: vision • retina • information • neural coding • graded potential INTRODUCTION toreceptors use against the noise, and how reliable are their graded voltage responses as neural representa- The ability to adapt to mean illumination allows a pho- tions of the dynamic contrast stimulation? toreceptor to gather and process information about rel- Drosophila photoreceptors have been successfully ative light changes (contrasts) over a vast range of in- used as a model system for analyzing insect phototrans- tensities without saturating its steady-state membrane duction. Recently, the transduction dynamics in dark- potential. The process of adaptation itself involves both adapted photoreceptors have been extensively studied the workings of the phototransduction cascade and the by patch-clamping dissociated cells (for reviews see photoreceptor membrane. The phototransduction cas- Hardie and Minke, 1995; Scott and Zuker, 1998), but cade is a signal pathway where a photoisomerized pho- the physiology and response properties of light-adapted topigment activates a cascade of intracellular biochemical photoreceptors have been largely ignored. The reason reactions, which modulates the opening of light-sensi- for this is simple: the in vitro preparation does not tive ion channels on the photoreceptor membrane. Its readily survive prolonged light stimulation; on the output is the light (or transduction) current. In turn, other hand, although the in vivo intact fly preparation the photoreceptor membrane has additional voltage- can survive hours of light adaptation, its small size has sensitive ion channels, which together with its capaci- made intracellular recordings very difficult. Conse- tance shape the changes in the light current into a volt- quently, only limited data, such as some basic noise age response. There are many physical factors that can analysis of the elementary responses (i.e., quantum constrain the fidelity of the photoreceptor voltage re- bumps) during light adaptation are available (Wu and sponses: the physics of photon absorption, the delays Pak, 1978; Johnson and Pak, 1986). This report is an and reproducibility of chemical reactions in the trans- extensive in vivo study of the response and membrane duction cascade, and the stochasticity in the ion chan- properties and light adaptation dynamics in Drosophila nel kinetics. So what kind of coding strategies do pho- photoreceptors at 25ЊC using linear signal and noise Address correspondence to Dr. Mikko Juusola, Physiological Labora- analysis with natural-like contrast stimulation. We tory, Downing Street, University of Cambridge, Cambridge CB2 3EG, found that the stronger light adaptation greatly im- UK. Fax: 44-1223-333-840; E-mail: [email protected] proves the photoreceptors’ information capacity. At 3 J. Gen. Physiol. © The Rockefeller University Press • 0022-1295/2001/01/3/23 $5.00 Volume 117 January 2001 3–25 http://www.jgp.org/cgi/content/full/117/1/3 low light intensity levels, the fidelity of photoreceptor of the microelectrodes inside a cell varied between 120 and 250 responses is limited by the photon shot noise. Amplifi- M⍀. Because recording from small photoreceptors requires very cation of single photon responses into individual de- sharp microelectrodes with good electrical properties, the resis- tance of the electrodes with a suitable shape (short shank with tectable events leads to noisy voltage responses, whose rapid taper to minimize the effects of intramural capacitance) was slow speed is set by the slow rate of the transduction re- measured before the actual experiments in a grounded salt drop. actions and matches the filter properties of the photo- This selection greatly increased the odds of good recordings. The receptor membrane. Such low frequency signaling time constant of the electrodes (␶e) in tissue after a dual capaci- keeps the photoreceptor information capacity low. On tance compensation of the amplifier (model SEC-10L; npi Elec- tronic) was Ͻ10 ␮s, giving a high cut-off frequency of Ͼ20 kHz. the other hand, in bright illumination, the Poisson Microelectrodes were mounted on a manual micromanipulator properties of the light provide a high fidelity contrast (model HB3000R; Huxley Bertram) and entered the compound stimulus. The voltage responses consist of a multitude eye through the previously prepared small hole. A blunt refer- of small and fast bumps, the photoreceptor membrane ence microelectrode, filled with fly Ringer’s (containing in mM: provides faster signaling, but the bump latency distribu- 120 NaCl, 5 KCl, 10 TES, 1.5 CaCl2, 4 MgCl2, and 30 sucrose), was mounted on the back of the fly’s head close to the eye. tion remains relatively unaffected and this now sets the Membrane potentials were recorded with the amplifier operat- ultimate speed limit of the voltage responses. Further ing in the compensated current-clamp (CC) or balanced bridge light adaptation does not improve the signaling fidelity mode. The recordings were carried out from green-sensitive R1-6 when the rate of the chemical reactions is already at its photoreceptor cells that are the dominant input to the Drosophila maximum in the majority of the transduction units. visual system (Strausfeld, 1989). Because we used red-eyed flies in- stead of the commonly used white-eyed mutations, which lack all Consequently, the photoreceptor information capacity the screening pigments, and provided the light stimuli through a -bits/s at a mean photon ab- small point source (see Light Stimulation), the effects of extracellu 300–200ف starts to saturate sorption rate of 3 ϫ 105 photons/s. lar field potentials on the recordings were minimal. The maxi- mum extracellular field potentials evoked by saturating light MATERIALS AND METHODS flashes measured in the retina were typically Ͻ5 mV. A successful photoreceptor penetration was seen as a 60–75-mV drop in the Animals and Preparation electrode potential and vigorous responses to low intensity light pulses. The input resistance of the photoreceptors in the dark was Flies, normal wild-type red-eyed Drosophila melanogaster, were ob- 700 Ϯ 540 M⍀ (n ϭ 9) and in fully light-adapted conditions, tained from a laboratory culture and reared at a constant tem- which depolarized the membrane 25–40 mV above the resting po- perature of 25ЊC.1–7-d-old flies were mounted with their head tential, 320 Ϯ 100 M⍀ (n ϭ 4). These values are much higher protruding from the open tip of a conical holder, whose hollow than those previously reported from intracellular recordings (Wu copper core was shielded outside with a ceramic insulator. Flies and Pak, 1978; Johnson and Pak, 1986), but similar to those mea- were fixed by their backs to the copper tip with a mixture of bees- sured using patch-clamp electrodes (Hevers and Hardie, 1995). wax and heat sink paste, and the proboscis was stretched to elim- By injecting a pseudorandomly modulated current into the cell inate vergence eye movements. This left the abdomen intact for and calculating the resulting membrane impulse response, we ventilation, allowing the fly to survive for up to 2 d. A hole, the could estimate the membrane time constant. In the dark, mem- size of a few ommatidia, was cut manually in the dorsal cornea brane charging could be approximated with a single exponential with a sharp razor edge and sealed with Vaseline. The holder was ms; when depolarized by a bright light 20ف time constant, ␶ mounted on top of a ceramic recording platform, where its cop-
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