Abstract Large motor aberrations were observed in the sand crab, Emerita analoga, allowed to concentrate DDT from seawater to 1.4 ppm. This is close to some levels found in the field. In recordings made from a nerve innervating the abdominal flexor muscles, 1 ppm DDT in the bathing medium greatly increases spontaneous neuronal bursting, length of tactually stimulated bursts and frequency of firing of the larger motor neurons. These effects appear cumulative and irreversible. Animals bathed in 100 ppb DDT and animals with 1.4 ppm DPT taken up over 12 days showed lesser but similar neurophysiological effects. Behavioral effects at concentrations found in the natural environment is deemed possible. 235 Introduction The effects of the insecticide DDT (11) on the nerves of various animals has been the focus of many neurophysiological studies in the past. These studies have mainly attempted to explain the mode of action and effect of DDT on single neurons. The changes shown in single cells are (a) repetitive afterdischarge and (b) prolongation of the action potential (6; 7). These two effects appear to manifest themselves behaviorly in hyperexcitability, ataxia, convulsion and death. Also DDT's effect both on single cells and on observable behavior increase with amount of exposure to DDT (3; 6; 8). This work, however, was all done using high concentrations of DDT far above levels found in the natural environment. Since DDT has effects which accumulate with exposure, it seems reasonable that more subtle behavioral effects may also occur before the obvious symptoms described. I believe that electrophysiological techniques may make a sensitive indicator of such subtle behavioral aberrations. This study focused on the question of whether levels of DDT found in the natural environment and levels that cause measurable motor changes in the 2 -2- laboratory overlap. I. Behavioral Analysis In order to test for gross behavioral effects 3 adult female sand crabs, Emerita analoga (Simpson), were placed in each of six 2 liter beakers containing 1 liter of constantly areated seawater, 1 cm. layer of sand and differing concentrations of DDT. Concentrations (in ppb (12)) of 5000, 1000, 100, 10, 5 and 0 (control) DDT were obtained by adding 1 cc. of acetone containing the appropriate amount of a mixture of DDT and C+4-DDT (10,000:1) to each beaker. Observations were made at least twice daily for the 12 day experimental period. One animal from each beaker was analyzed for amount of DDT taken up after the 12 days. The C+-DDT was extracted 3 times with 10 mls. petroleum ether from a 50% glacial acetic:50% perchloric acid digest of the animal. The extract was evaporated to approximately 1 ml.. mixed with 10 mls. of toluene scintillation fluid and counted using a liquid scintillation counter (Nuclear¬ Chicago, Unilux II). The remaining animals were saved for neurophysiological analysis. Refer to Table I for the results of these studies. II. Neurophysiological Analysis Animals were pinned ventral side up with their 2 -3- abdomens extended and dissected to expose the third and fourth abdominal ganglia. Seawater between 14 and 19° C was used as a bathing medium (10). Electrophysiological recordings were made with a single suction electrode (the nerve was cut distill to the electrode). Nerve activity was displayed on an oscilloscope and photographed. Tactile stimulation was done by touching or brushing with a glass rod. Electrical recordings of neural activity were made before and after the introduction of DDT. The DDT solutions were the same as described in section I as was the 0.1% acetone control. The one preparation which had taken up DDT from the 100 ppb solution of section I (1.4 ppm whole animal concentraion) was dissected and recordings made in seawater. Characterization of Nerves Studied Results of the anatomical study are shown in figure 1. The nerve (ng) studied leaves the nerve cord between the third and fourth abdominal ganglia and apparently innervates the fast flexor muscles of the fourth abdominal segment. Six different neurons were identified by their spike shapes (figure 24) though a seventh may be present (figure 2B). This seventh spike, labeled 3', was usually seen next to 3 in photographs and with its similar shape and heigth may be the same. 24 Neurons 1 and 2 seem to be inhibited (these are normally firing all the time) while one of the larger neurons, believed to be spike 4, is firing. This is shown in figures 3E and 4E. Short bursts of activity could be elicited from the nerve, ng, by tactile stimulation of either the head region (particularly the antennae) or the telson region. Tactile stimulation to the telson still gave bursting after the nerve cord was cut anterior to the third ganglion. A cut was then made just below the third ganglion and bursting could no longer be elicited by telson stimulation. In another preparation when the nerve cord was cut just below ny, anterior to the fourth ganglion, tactile stimulation to the head region still elicited bursts. I concluded that the nerve ny is associated primarily with cells in the third abdominal ganglion. Telson stimulation, however, may not elicit all 6 spikes, leaving the possibility that some of these motor neurons may come directly from higher centers (i.e. more anterior). Also, all 6 neurons may not have been recorded in these animals so a small number of the cells could come from the fourth ganglion. Spiking activity in the nerve, ng, usually exhibits "size princinle" (2); the smaller spikes (smaller motorneurons) firing much more often while the larger spikes are harder to elicit and occur near -5 the center of bursts when all neurons are firing. This is shown in the fast traces in figure 2. The Effect of DDT One ppm DDT caused an increase in both the amount of spontaneous bursting (figure 3) and the length of bursts elicited tactually (figure 4). In the seven preparations done at this concentration, spontaneous bursting occurred 5 to 30 minutes after DDT was applied. By 60 minutes, firing of neurons 1 thru 4 was nearly continuous; large bursts, that included neurons 5 and 6, were as frequent as every 5 to 10 seconds. After 60 minutes, tactually elicited bursts continued 5 to 30 seconds after stimulation. Previously quiescent spike 6 fired frequently after DDT treatment. Attempts to reverse the effects by returning the animal to seawater were not sucessful. Two control preparations were run and these showed only isolated spiking (neurons 1-4) and infrequent small bursts (approx. one every 20-30 minutes). The two largest neurons could not be elicited. A bathing liquid concentration of 100 ppb DDT elicited spontaneous bursting only after 1 hour and this never reached the level seen with the higher concentration solution. The length of bursting elicited tactually, however, increased markedly and very large bursts containing all the neurons were 24 -6 common under these conditions. DDT treatment in all these cases increased the output of normal firing in ng; coordination of the spikes, as viewed through the "size principle" and inhibitory neuronal responses, remained as before treatment. In the one preparation taken from the 100 ppb DDT solution of section I (1.4 ppm whole animal concentration) recordings were made in seawater. Though little spontaneous bursting occurred, tactually stimulated bursts continued for 2 to 12 seconds after stimulation. clearly longer than either control. Also neurons 5 and 6 could be easily tactually elicited. Again the coordination between neurons appeared normal. Discussion The behavioral observations of the first section indicate that a whole animal concentration of 1.4 ppm is about at the threashold where large behavioral effects can be observed. While most of the DDT found in Emerita in the field is probably stored in lipids, under the experimental conditions the crab might not have been able to transfer much to the lipids, leaving more free to be taken up by the nervous system. Nevertheless, this level is comparable to the 0.92 ppm DDT or 1.2 ppm DDT plus DDD concentrations found in animals from the Los Angeles area (1). (This ag second concentration may actually be more meaningful since somewhat similar effects to those of DDT have been reported for the metabolite DDD (3).) The neurophysiological results show that 1 ppm DDT increases neuronal discharge in at least na. This is consistent with the present theory on the mechanism of DDT action which proposes that the DDT treated membrane remains depolarized for a longer than normal time after a spike has fired (4; 5; 6; 7; 8; 9). The effect on tactually stimulated bursts and the ability of the larger neurons (particularly 6) to fire seem the more sensitive indications of change; these are most clearly seen in the lower concentration (100 ppb) and uptake (1.4 ppm whole animal concentration) preparations. Finally, if Davis' concept that recruitment of larger motorneurons results in more forceful movements (2) applies here then behavioral aberrancies might be expected at low concentrations wherein neurons 5 and 6 fire at rates higher than controls. Summary The nerve of the sand crab, Emerita analoga, which leaves the main nerve cord between the third and fourth abdominal ganglia innervates what appears to be the fast flexor muscles of the fourth abdominal segment. Six motor axons have been identified, though a seventh 245 -8 may be present; spikes 1 and 2 seem to be inhibited while neuron 4 is firing. Bursting activity occuring during tactile stimulation of the head region or telson seems associated with cells in the third abdominal ganglion. "Size principle" was demonstrated and discussed. Gross motor effects were observed in animals allowed to absorb DDT from seawater. Animals whose whole body concentrations reached 1.4 ppm DDT were seen to exhibit large motor effects yet not die within 12 days. This level is close to that reported for some Emerita in the natural environment. Neurophysiological recordings show that 1 ppm DDT in the bathing medium of a dissection greatly increases (1) amount of spontaneous bursting (2) length of tactually stimulated bursts and (3) the frequency of firing of the larger motorneurons. These effects seemed to increase with exposure to DDT and could not be reversed. Lower concentrations (100 ppb) and animals which had taken up DDT in the behavioral studies showed lesser but similar effects; the continuance of tactually elicited bursts and the frequency increase in the large neuron's firing were the most prominent results. The increased activity generally seemed to leave coordination between spikes unchanged. The possibility of behavioral effects at concentrations found in the natural environment are discussed. Acknowledgments I would like to thank the faculty and students of Hopkins Marine Station for their interest and encouragement. In particular Dr. George Mpitsos and Mr. Robin Burnett have been a continual help during all parts of this study except in fucking around with editing the paper. 24 -10- References and Notes 1. Burnett, R. Science. (submitted). Davis, W.J. 1971. Functional significance of motorneuron size and soma position in swimmeret system of the Lobster. J. Neurophysiol. 34: 274. 3. Lalonde, D.I.V., and A.W.A. Brown. 1954. The effects of insecticides on the action potentials of insect nerve. Can. J. Zool. 32: 74. 4. Matsumara, F., and R.D. O'Brien. 1966a. Absorbtion and binding of DDT by the central nervous system of the American cockroach. J. Agr. Food Chem. 14: 36. Matsumara F., and R.D. O'Brien. 1966b. Interactions of DPT with components of American cockroach nerve. J. Agr. Food Chem. 14: 39. 6. Narahashi, T., and H.G. Haas. 1967. DDT: Interaction with nerve membrane conductance changes. Science. 157: 1438. Narahashi T., and T. Yamasaki. 1960a. Mechanism of increase in negitive afterpotential by dicophanum (DDT) in the giant axons of the cockroach. J. Physiol., (London). 152: 122. 8. Narahashi, T., and T. Yamasaki. 1960b. Behaviors of membrane potential in the cockroach giant axons poisoned by DDT. J. Celluar Comp. Physiol. 55: 131. O'Brien, R.D., and F. Matsumara. 1964. DDT - A new hypothesis of mode of action. Science. 146: 657. Paul, D.H. 1970. Swimming behavior of Emerita analoga 10. (Crustacea, Anomura): A Neurophysiological analysis. PhD. Thesis. Stanford University. 11. DDT stand for 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane. ppm stands for parts per million (ug/g 12. ppb stands for parts per billion (ug/g). Both are per gram wet weight when animals concentrations are referred to. 25 1 a 0 + — 1 — oo o oO 5 o20d E 2 2 oo — 2 OS . a 2 o c 1 on aa. d 1 1 5 — 0 2 a oE oo o O O o + 5 u a 0 + 55 o —2 CD C Figure A. The undissected abdomen with the telson extended. B. Dissection showing the third thru fifth abdominal ganglia. Electrophysiological recordings were from ng. o kaa- l S aen Figure 2. A. Six different identified spikes from ny are shown. B. Spikes 3 and 3' are shown. Since they differ only slightly in size and shape and usually occur close together they could be from the same neuron. - 2 - - 4 2 7. 953 Figure 3. Spontaneous activity seen in the nerve n- after application of DDT. (A) before DDT applièation; (B) 10 minutes after application; (C) 30 minutes; (D) 45 minutes; (E) 60 minutes. Trace E also shows inhibition of spikes 1 and 2 during spike 4. Gain: A-D .5 mV/cm. .2 mV/cm. 26 O Figure 4. Activity elicited by tactile stimulation of the head region after DDT application. (A) before DD application; (B) 20 minutes after application; (C) 30 minutes; (D) 45 minutes; (E) 60 minutes. E shows the inhibition of the two small spikes during spike 4."" indicates start of stimulation; "" indicates cessation of stimulation. Gain: A-D .5 mV/cm. .2 mV/cm. 2