0 THE INITIATION AND SPREAD OF ACTIVATION OE THE IRIDOPHORE CELLS IN THE SOUID LOLIGO OPALESCENS Annette C. Cholon Hopkins Marine Station Spring Class 198 ABSTRACT The squid Loligo opalescens exhibits iridescent colors in its third der mal layer through the action of a specific cell type, the iridophore. Although much is known about the neural control of the squids pigmented chromatophore organs, little is known about the action of iridophore cells, other than the neurotransmitter acetylcholine is responsible for their activation. This paper sets out to examine the possible mechanism of ACh delivery to the iridophore cells, through an analysis of the activation and spread of iridescence in response to electrical stimulation. INTRODUCTION The skin of the common market squid, Loligo opalescens is capable of rapid changes in both color and pattern. These changes are effected through the action of two cell types, chromatophores and iridophores. Together, chromatophores and iridophores allow the squid to camouflage themselves from predators and to signal to othe members of the species. The most spectacular displays of color are produced by the iridescent iridophore cells, which may reflect light in metallic hues of pink, green, blue, orange and yellow. The organization of color producing cells into units and patterns has been well described. (Hanlon,1982). Iridophores appear in two basic arrangements, dorsal splotches and ventral sheets. The dorsal splotches are arranged as rings, which our lab has fondly nicknamed doughnuts", and contain a number of iridophore cells with a chromatophore in the center. The ventral sheets are a more ordered array of iridophore cells, arranged as continuous sheets of color. Iridescent cells known as reflector cells cover the optic lobes, ink sacs and various internal organs of the squid. Both reflector cells and iridophore cells are characterized by non-pigmented arrays of thin membrane bound platelets. In both cell types, these platelets are of a higher refractive indexs than the material around them, and reflect light to produce structural colors. The basic difference between reflector cells and iridophores is in the orientation of the platelets. In iridophores the platlets are oriented on edge relative ot the skin surface, while in reflector cells they are flat with a broad surface facing out (Brocco & Cloney, 1980). It is thought that iridophores produce structural colors by acting either as a thin film interference device or as a diffraction grating. (Brocco & Cloney, 1980; Land,1972). The basic difference between iridophores that are in a non-iridescent and those in an iridescent state is in the ultrastructure of the platelets, which coalesce from a non uniform to highly structured material of uniform refractive index (Cooper & Hanlon, 1986). It has been reported that the pigmented chromatophore organs are under neural control. (Cloney & Florey, 1968; Mirow,1972; Cloney & Brocco, 1983). However, little is known about the control of iridophore cells. Previous investigation has shown the neurotransmitter, acetylcholine (ACh) to be a key factor in the activation of structural changes in iridophore cells. Although ACh has been found in the dorsal mantle iridophore der mal layer of L. brevis at levels of 1 nmol Ach mg * protein, nothing has yet been deduced about the delivery of the ACh to the cells, as the presence of nerves has not yet been anatomically established (Cooper & Hanlon, 1986). Several possible mechanisms for ACh delivery do exist. One is that the ACh diffuses across a distance, originating in the chromatophore layer. Another is that the ACh is delivered through the circulatory system, acting almost as a hormone. A third possibility, also the most likely, is that the iridophores are innervated by a very fine nerve structure which releases ACh at its terminals. This paper sets out to examine the possible mechanism of activation of the iridophore cells, how the ACh is delivered, and to quantify the spread and intensity of iridescence produced as iridophores are activated. METHODS AND MATERIALS Schooling L. opalescens caught locally in Monterey Bay were kept in running sea water tanks. Both male and female squid were used, with males being used more often because of their greater size. Unless otherwise noted, skin preperations were made by first decapitating the squid and then removing all of the internal organs, including the gladius. The mantle was then pinned out, and the first two dermal layers were peeled off. The remaining third layer, containing the iridophores, was left on the mantle to prevent any damage to possibly existing nerves. The preperation was periodically run under natural seawater to retain its viability. Circulatory experiments were run with the internal organs of the squid intact. Glass microelectrodes were used to cannulate various major arteries and viens, including the celiac arteries and cephasic viens. All experiments relating to neurophysiology were perfor med on the common mantle preperation. Electrical stimulation was performed through a fine glass suction electrode. Stimulation was carried out at differing parameters: voltage ranged between 3V to 30V, frequency of 1 to10Oper second, with duration 6 to 6ms However, the parameters of 3V, 100 shocks per second, and 6 ms duration were shown to be most effective and used for the majority of the experiments. Results were observed through a Wild dissecting microscope, and recorded on a VCR using a Hitachi Video Camera. Mantle preperations were immersed in 50 ml bathes of various agents to test for the activation of iridophores by electrical stimulation. The solutions were in concentrations as follows: TTX - 1x10*° in natural sea water; high Ca' - natural sea water + 50 mM Cacl»; high Zn'- natural sea water + 10mM ZnCl; 0 Na’- Tris replaced Na’ in artificial sea water; 0 Ca’- 0 Ca' artificial sea water; high Mg' - 60mM MgCl, in artifiial sea water; Scopolamine - 1x10 4 in natural sea water. Quantitative analysis of video taped data was performed on a Mega Vision Image Processor. RESULTS Injecting ACh into the circulatory system of the squid resulted in no change in the status of the iridophores, or even of the chromatophores. Varying concentrations of 1x10-7, 1x10-6, 1x10-4 were all tried. Neither injections into the major arteried nor into the major viens proved effective in activating the iridophores to produce iridescence. Bath applied ACh at a concentration of 1x10-6 after negative injection results did activate the iridophores, thus the skin of the preperations was still viable. Direct electrical stimulation of the third dermal layer of skin proved to be much more fruitful. A single shock of 7.5V or greater produced iridescence in a single, or a few iridophores. Multiple shocks of 3V at a frequency of 100 per second for 1 to 5 seconds activated large numbers of iridophores in a single doughnut, with a ring size of about 2.5mm, and often caused the activation of iridescence to spread to adjacent rings up to almost Smm away. Once it was established that electrical stimulation was possible in activating iridophores, various solutions were applied to the mantle preperations, with results illustrated in Table 1. Video tapes taken of the stimulation of iridophores in different solutions were then analysed on the Image analyser. Images of the iridophores at differents times during the activation process were projected upon the screen. The image was mapped, and the percentages of white pixels in each picture represented the area of iridophore activation. The results from such analysis of both contross (in natural sea water) and of experimental preperations in high Mg- and Scopolamine can be seen in figure 1 and figure2. The actual time of activation through electrical stimulation of the iridophores ranged between 10 and 60 seconds, with a peak intensity appearing between 30 and50 seconds. The deactivation of the iridophores was much longer and more varied, ranging between 5 and 30 minutes while under running sea water. It was observed that during activation the iridophores passed through various stages of color, intensity and density. Upon initial stimulation the iridophores often began iridescing yellow and blue, later turning to the more common pink and red stage. The spread of iridescence did not appear to occur in concentric circles about the electrode tip. Rather, it occured randomly within a ring, with a few iridophores in various locations activating, to later be joined by others between them, thus increasing the density of activated within a doughnut. (see figures 3 and 4). DISCUSSION The negative results of the circulatiory injection experiments, coupled with the activation of iridiphores through electrical stimulation lead one to believe that ACh is not carried through the circulatory system to activate iridophore cells. This, in any event, seemed unlikely from the start, as Ach is easily degraded in the curculation, and if carried in the blood, would affect many other organs besides the iridophores. It is also clear that ACh is not only delivered as a secondary response to chromatophore activity. Direct observation of the squid showed that the iridophores did not activate each time the chromatophores expanded, and that their activation was selective to the animals particular behavior. There are several possible explanations for the fact that electrical stimulation activates iridophores. One possivility is that voltage gated channels are being opened due to the voltage change caused by the shock. Although this may account for the activation of iridiphores directly beneath the electrode, it in no way explains the iridescence produced in peripheral iridophores, far from the area of direct stimulation. Another possibility is that the iridophores are electrically coupled. That is, that all of the iridophores in a single doughnut are directly connected by gap junctions. Because an assay for gap proteins was not performed, this possibility can not be discounted. However, the activation of peripheral iridophores, as far away as in an adjacent ring, seems to weaken the possibility of the existance of gap junctions. A third and more likely explanation for the activation of iridophores through electrical stimulation is that the iridophores are all connected through a fine network of nerves. The fact that a higher frequency of stimulation increases the spread of iridophore activation suggests that some kind of facilitated activation is talking place. The high frequency of stimulation may build upon action potentials, thus allowing them to traverse several synapses to activate a large number of iridophore cells within the network. The possible innervation of iridophore cells is also supported through the preliminary results of stimulation experiments in several different bath applied solutions (see results Table 1). Sodium is needed to carry action potentials along nerves, thus the failure of the spread of iridescence in zero sodium, as well as a partial blockage of spread in TTX, implies that nerve function may be hindered. This result is strengthened by iridophore failure in zero calcium solution, as calcuim is also quite necessary for nor mal nerve transmission. Magnesium blocks calcium channels at neural synapses, thus a high magnesium solution would block the efficacy of synaptic transmission. Scopolamine, working as an ACh antagonist also blocked the spread of iridophore activation. Therefore, the results of these preliminary experiments suggest that nerves of some kind may possibly be involved in the activation and spread of iridophore iridescence. Examination of the time courses analysed on the image processor show clearly that iridophore activation does not occur in concentric circles, spreading away from the electrode. Rather, the iridophores light up randomly with their density increasing as more and more are activated. The image processed data also shows that most of the iridophores show a similar time course of activity, with a peak intensity of brightness reached about 30 to 50 seconds after stimulation. It is interesting to note that those iridophores which are brightest at first also seem to fade first. In summary, the preliminary evidence presented here indicates that the iridophore cells of squid L. opalescens could possibly be under neural control, with a fine network of nerves present in the third dermal layer. Thus, ACh could be delivered at these nerve terminals, and not from a distance or through the circulation. However, many experiments remain to be performed before any solid conclusions about the presence of nerves in the third layer can be made, the most obvious of which is a thorough anatomical search. A great deal of analytical potential also lies in the use of the Mega Vision Image Processor, which presents a good method of quantifying the spread and intensity of iridescence. Overall, the study of the activation of iridophore cells may lead to a better understanding not only of squid behavioral color patterning, but also of the nervous control of other ACh based systems. O ACKNOWLEDGEMENTS I am grateful to Dr. Stuart Thomson for his advice, patience, and encouragement, to Dr. William Gilly for his help, and to Natasha Fraley for being kind enough to let me use her equipment and office. O TABLE 1. IRIDIPHORE RESPONSE IN VARIOUS SOLUTIONS Bolution Iridescence TTX I 10-6 + - SCOPOLAMINE 110-41 HIGH MG¬ + - - - - - oca¬ - - - - O Na¬ + - O Na-//w/Li- +- - partial blockage of iridescence --- - - full blockage of iridescence C cte dere 3 0 00 160 o G- a 2 0 20 30 TIME(SEC) 40 CONTROL SCOPOLAMINE + 50 60 FIGURE 4 REFERENCES Brocco, S.L., Cloney, R.A.: Ref lector Cells in the Skin of Octopus dofleini. Cell Tissue Res. 205, 167-186 (1980) Chichery,R., Chichery, M.P.: Motor and Behavioural Effects Induced by Putative Neurotransmitter Injection into the Optic Lobe of the Cuttlefish, Sepia Officinalis . Comp Biochem Physio. 80c, No.2, 415-419 (1985) Cloney, R.A., Brocco, S.L.: Chromatophore Organs, Reflector Cells, Iridocytes and Leucophores in Cephalopods, Amer. Zool., 23, 581-592 (1983) Cloney, R.A., Florey, E.; Ultrastructure of Cephalopod Chromatophore Organs, Z. 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