Cholinergic Modulation of Dopamine Release and Horizontal Cell Coupling in Mudpuppy Retina

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1 Pergamn PII: S (96) Visin Res., Vl. 36, N. 24, pp , 1996 Cpyright 1996 Elsevier Science Ltd. All rights reserved Printed in Great Britain /96 $ Chlinergic Mdulatin f Dpamine Release and Hrizntal Cell Cupling in Mudpuppy Retina KAREN L. MYHR,* JOHN S. McREYNOLDS*t The effects f chlinergic agnists and antagnists n electrical cupling between hrizntal cells were studied in dark-adapted mudpuppy retinas. Carbachi and the nictinic agnist 1,1-dimethyl- 4-phenylpiperazinium (DMPP) uncupled hrizntal cells, but the muscarinic agnist xtremrine did nt. The uncupling effects f carbachl and DMPP were blcked by the nictinic antagnist D-tubcurarine and by the dpamine antagnist fluphenazine, indicating that carbachl uncupled hrizntal cells by stimulating dpamine release via nictinic receptrs. Carbachl als caused an increase in release f [3H]dpamine frm retinas. D-Tubcurarine increased hrizntal cell cupling, indicating that tnic chlinergic input was present in dark-adapted retinas. D- Tubcurarine did nt reduce light-evked uncupling f hrizntal cells, suggesting that chlinergic neurns are nt an essential part f the direct pathway by which light causes an immediate increase in dpamine release. Cpyright 1996 Elsevier Science Ltd Retina Hrizntal cell Electrical cupling Acetylchline Dpamine Mudpuppy INTRODUCTION Electrical cupling between hrizntal cells is ne f the many prcesses mdulated by dpamine in the vertebrate retina [reviewed in Negishi et al. (1990); Dwling (1991); Witkvsky & Dearry (1992); Djamgz & Wagner (1992)]. Dpamine decreases hrizntal cell receptive field size (Teranishi et al., 1983; Mangel & Dwling, 1985; Picclin et al., 1984; Dng & McReynlds, 1991) by decreasing gap junctin cnductance (Lasater & Dwling, 1985; DeVries & Schwartz, 1989). Changes in the state f light/dark adaptatin als affect hrizntal cell receptive field size (Mangel & Dwling, 1985; Dng & McReynlds, 1991; Baldridge & Ball, 1991), althugh this relatinship appears t differ amng species. In mudpuppy, lightevked uncupling f hrizntal cells is mediated by dpamine (Dng & McPeynlds, 1991). Light has als been shwn t stimulate dpamine release in anther amphibian, Xenpus (Batright et al., 1989). In additin t dpamine, there is evidence that ther neurtransmitters als affect hrizntal cell receptive field size. GABA (Teranishi et al., 1983; Picclin et al., 1982; Dng & McRe.ynlds, 1992), acetylchline (Marshall & Werblin, 1978; Negishi & Drujan, 1979; Hare & Owen, 1995), sertnin (Negishi & Drujan, 1979; Drujan et al., 1990) and nitric xide (Miyachi et al., 1990; Baldridge et al., 1993; Mills & Massey, 1993) *Department f Physilgy, The University f Michigan, Ann Arbr, MI , U.S.A. tt whm all crrespndence shuld be addressed [ jsm@ umich.edu]. decrease hrizntal cell receptive field size in varius species. All f the abve except nitric xide appear t affect hrizntal cell cupling by mdulating dpamine release. Acetylchline (ACh) decreases the receptive field size f hrizntal cells in fish (Negishi & Drujan, 1979) and tiger salamander (Marshall & Werblin, 1978), by stimulatin f dpamine release (Negishi & Drujan, 1979; Hare & Owen, 1995). Hwever, these studies did nt prvide any infrmatin n the type f chlinergic receptrs invlved, r whether chlinergic neurns were in the pathway by which light mdulates dpamine release. The present study prvides evidence that ACh als uncuples hrizntal cells in mudpuppy by stimulating dpamine release at nictinic receptrs, and that the chlinergic neurns are nt an essential part f the pathway by which light causes uncupling f hrizntal cells. METHODS Experiments were perfrmed in dark-adapted retinas in the eyecup f the mudpuppy, Necturus maculsus. The preparatin, electrical recrding and ptical stimulatin systems have been described in detail previusly (Dng & McReynlds, 1991; Myhr et al., 1994). Mudpuppies (Kns Scientific, Germantwn, WI) were kept in an aquarium n a 12 hr light/dark cycle and experiments were dne in the afternn prtin f the light cycle. All prcedures were dne under infrared illuminatin using animals that had been dark adapted vernight. The eyecup was munted in a chamber and superfused at a 3933

2 3934 K. L, MYHR and J. S. McREYNOLDS A B C c 120 s 2.0,_.,I C) n," uj 1.5 co I-- 09 ~1~ 20 s CARB OO O O I I I I TIME (min) FIGURE 1. Carbachl increases cupling between hrizntal cells. (A) Dwnward deflectins f respnse trace are hrizntal cell respnses t alternating spt and annulus stimuli (first respnse is t a spt). Letters abve respnse trace indicate pairs f spt and annulus respnses which are shwn n a faster time scale in (C). Hrizntal line belw the respnse trace indicates superfusin with 50 pm carbachl. During the 2 min gap in the respnse trace the retina was stimulated with dim slits f light at different psitins (nt shwn) and n spt r annulus stimuli were given. (B) Plt f nrmalized spt-annulus respnse rati (see Methds) vs time. Data pints are pltted at the times f the spt stimuli in each pair. (C) Pairs f spt and annulus respnses, crrespnding t the letters abve the trace in (A), n a faster time scale. Spt and annulus intensity, 9.3 lg Q. rate f 0.5 ml/min with Ringer slutin (in mm: NaC1, 110; KCI, 2.5; MgC12, 1.2; CaC12, 1.8; glucse, 11; HEPES buffer, 5.0, adjusted t ph 7.8). The superfusate culd be switched t alternate Ringer slutins cntaining knwn cncentratins f neurtransmitter agnists and/r antagnists. Oxtremrine and nmifensine were purchased frm Research Bichemicals, Inc. Unless therwise nted all ther drugs were purchased frm Sigma Chemical C. Intracellular recrdings were made with cnventinal electrnics and 3 M K+-acetate-filled micrpipettes with resistances f Mf~ measured in the Ringer slutin. Respnses were stred n magnetic tape and played back later nt a chart recrder r digitized at 167 Hz fr further analysis. Light stimuli (spt and annulus patterns, r diffuse adapting lights) were prjected nt the retina after passing thrugh a 560 nm interference filter. Timing and intensity f the light stimuli were cntrlled by electrmagnetic shutters and calibrated neutral density filters. Fr each intensity, the stimulus energy at the plane f the retina was measured with a calibrated UDT-555D phtdide (UDT Sensrs, Inc.) and cnverted t quanta/cm/sec. In figure legends stimulus intensities are given in lg Q, where Q = quanta/cm/sec. Hrizntal cells were identified by their large hyperplarizing respnses t diffuse illuminatin, large receptive fields and relative depth in the retina. After a hrizntal cell was penetrated, its receptive field center was lcated by determining the psitin at which tw perpendicular slits f light each prduced a maximal respnse. All stimuli were centered n this psitin. Only thse cells whse maximum respnse amplitude was 25 mv r greater were used in these experiments. Changes in hrizntal cell cupling were inferred frm relative changes in hrizntal cell respnses t tw light stimuli: a small spt stimulus (200 r 400 #m dia) in the receptive field center and a cncentric annulus stimulus (i.d. 600 r 900 #m,.d #m). All spt and annulus stimuli were f less than half-saturating intensity. As described in detail earlier (Dng & McReynlds, 1991), an increase in the rati f spt respnse amplitude t annulus respnse amplitude indicates a decrease in hrizntal cell receptive field size (effective cupling), and vice versa. Since a change in hrizntal cell receptive field size culd be due t changes in membrane cnductance, gap junctin cnductance, r bth, the abslute changes in either f these cnductances cannt be determined by this methd. Hwever, when the spt and annulus respnses change in ppsite directins, as in the present experiments, the majr change must be in the gap junctin cnductance between hrizntal cells. In this paper we will refer t an increase in spt-annulus respnse rati as an uncupling f hrizntal cells, with the understanding that this may include changes in membrane cnductance as well as gap junctin cnductance. Fr a given experiment, the effect f a test substance was calculated as the relative change in the spt-annulus respnse rati. This was calculated by dividing the spt-annulus respnse rati in the presence f the drug (mean f five pairs f respnses at the time f the maximal drug effect) by the cntrl spt-annulus respnse rati (mean f five pairs f respnses immediately befre applicatin f the test substance). The effect f a given substance is summarized as the number f cells, the mean change in the spt-annulus respnse rati, and the significance (P value, paired t-test) f this change. Fr dpamine release experiments, retinas were islated frm eyecups prepared as described abve, under infrared illuminatin. In each experiment tw retinas were incubated fr 20 min in 1 ml f Ringer slutin cntaining 0.42 #M 3,4 dihydrxy[7,8-3h(n)]- phenylethylamine (Amersham), washed in fur changes f Ringer slutin, and transferred t a small chamber (NuclePre membrane hlder) where they were superfused with Ringer slutin fr an additinal 30 min at a rate f 0.5 ml/min befre beginning sample cllectins. One milliliter f superfusate was cllected every 2 rain using a Gilsn mdel 203 fractin cllectr. The superfusate culd be switched frm cntrl Ringer t

3 CHOLINERGIC MODULATION IN MUDPUPPY RETINA 3935 A n," uj 09 0 Q. O0 UJ n, O0 =, <, I-- Q joo % C. ( ~ ( ~.... CARB CARB CONTROL I I I I FLUPHENAINE _.% c~65. ] I I I TIME (min) FIGURE 2. Fluphenazine blcks carbachl-induced uncupling f hrizntal cells. (A) Plt f nrmalized spt-annulus respnse rati vs time during superfusin with 50 mm carbachl. (B) Same as (A) but in the presence f 40 mm fluphenazine. Superfusin f carbachl began 57 min after additin f fluphenazine. Spt-annulus respnse ratis in (B) were nrmalized with respect t thse measured in fluphenazine just befre the additin f carbachl. During the perids where n data pints are shwn n spt r annulus stimuli were given. Spt and annulus intensity, 9.3 lg Q. Ringer cntaining 50 #M carbachl r high ptassium (40mM KC1 substituted fr NaC1). All slutins, including the incubatin slutin, cntained 15/tM pargyline and 2-20 #M ascrbic acid. All slutins except the incubatin slutin cntained the dpamine uptake inhibitr nmifensine (2-20 #M). The entire experiment was carried ut in darkness. Fllwing the experiment, 5 ml f scintillatin ccktail (Scintiverse BD, Fisher) were added t each vial and mixed thrughly. The labeled dpamine remaining in the retinas was measured by putting them in 5 ml scintillatin ccktail. Radiactivity was measured in a Packard Tricarb 2100TR scintillatin cunter. Accrding t Rashid et al. (1993), mst f the tritium released frm fish retinas laded with this prcedure was in [3H]dpamine. RESULTS Carbachl uncuples hrizntal cells Figure I(A) shws the effect f carbachl n cupling f hrizntal cells. The dwnward deflectins f the respnse trace are hrizntal cell respnses t alternate flashes f a small spt, centered in the cell's receptive field, and a cncentric annulus f the same intensity. The first respnse in the trace is t the spt stimulus. During the time indicated by the hrizntal line belw the respnse trace, the superfusate was switched t Ringer cntaining 50 pm carbachl. Carbachl increased the amplitude f the spt respnse and decreased the amplitude f the annulus respnse, indicating that it uncupled hrizntal cells. Figure I(B) is a plt f the individual spt-annulus respnse ratis, each relative t the cntrl spt-annulus respnse rati befre applicatin f carbachl, n the same time scale as the respnse trace in Fig. I(A). Figure I(C) shws individual pairs f spt and annulus respnses n a faster time scale, at the times indicated by the crrespnding letters abve the respnse trace in Fig. I(A). In the cntinued presence f carbachl the effect n hrizntal cell respnses usually reached a maximum after several minutes and then declined. Similar effects f carbachl were seen with carbachl cncentratins frm 1 t 100 pm. A nearly maximal uncupling effect was seen with 50 pm carbachl, which increased the spt-annulus respnse rati by a factr f (mean SD, n = 17 cells, P < 0.001). In sme cells a secnd applicatin f carbachl was given after recvery frm the first applicatin. In all cases the effect f the secnd applicatin was the same as that f the first applicatin, indicating that there was cmplete recvery frm any desensitizatin that may have ccurred during the first applicatin. Dpamine antagnist blcks the uncupling effect f carbachl The uncupling actin f carbachl was mst likely via a stimulatin f dpamine release, since it was blcked by the dpamine antagnist fluphenazine (Fig. 2). The upper plt (A) (the same as plt B in Fig. 1) shws the effect f 50 #M carbachl n the spt-annulus respnse rati in nrmal Ringer. After recvery frm carbachl, 40 #M fluphenazine was added t the superfusate. This caused a decrease in the spt-annulus respnse rati due t blcking the actin f endgenus dpamine release, as described previusly (Dng & McReynlds, 1991). The lwer plt (B) shws the effect f 50 #M carbachl, 57 min after the additin f fluphenazine. In the presence f fluphenazine, carbachl had n effect n the sptannulus respnse rati. In fur cells, 50 pm carbachl increased the spt-annulus respnse rati by a factr f 1.35 _ 0.20 in cntrl Ringer and by 0.98 _ 0.11 in the presence f fluphenazine. A paired t-test indicated that the difference between the effect f carbachl in the presence vs absence f fluphenazine was significant (P = 0.039). The uncupling actin f carbachl is via nictinic receptrs Like carbachl, the nictinic agnist 1,1-dimethyl-4- phenyl-piperazinium (DMPP) uncupled hrizntal cells. DMPP (2 #M) increased the spt-annulus respnse rati by a factr f (n = 9, P < 0.001), and in ne ther cell it increased the spt-annulus respnse rati by a factr f As with carbachl, a secnd

4 3936 K.L. MYHR and J. S. McREYNOLDS 1.5 A 2.5 CONTROL 1.4 B z::::)~ 1.3 I O 0...,2 I~I 1.1 < T I I 2.0 O 1.5 LU CO O LU rr"? ?..a.o..o.... LIGHT I I I 0.9 CARB CARB DMPP DMPP + + DTC DTC FIGURE 3. Effects f chlinergic agnists n spt-annulus respnse rati. Effects f agnists are shwn in nrmal Ringer (filled bars) and in the presence f 100 mm DTC (pen bars). Bar heights shw mean spt-annulus respnse rati at the peak f the agnist effect relative t the spt-annulus respnse rati befre the additin f the agnist. Errr bars indicate 1 SD. The effect f DTC n DMPP-evked uncupling was tested in tw cells and n carbachl-evked uncupling in three cells. DTC significantly blcked the effect f the agnists (P < 0.001). applicatin after recvery frm the first was equally effective. In cntrast, the muscarinic agnist xtremrine (1-100 ~M) had n significant effect n spt and annulus respnse amplitudes in any f the 15 trials in seven cells. The nictinic antagnist D-tubcurarine (DTC), at a cncentratin f 100/~M, decreased the spt-annulus respnse rati in five f seven retinas tested (t , n = 7,P = 0.014). The fact that DTC caused a change in spt-annulus respnse rati ppsite t that caused by carbachl suggests that there was sme tnic chlinergic stimulatin f dpamine release in darkadapted retinas. DTC als blcked the uncupling effects f carbachl and DMPP. In the presence f 100 #M DTC, neither 50/~M carbachl r 2/~M DMPP had any effect n spt and annulus respnses (Fig. 3). Nictinic antagnists d nt blck light-evked uncupling f hrizntal cells It was previusly shwn that diffuse adapting light causes a dpamine-mediated decrease in hrizntal cell cupling in dark-adapted mudpuppy retina (Dng & McReynlds, 1991). Figure 4 shws the effects f a 30 sec adapting light n the spt-annulus respnse rati in a hrizntal cell in nrmal Ringer (A) and in the presence f DTC (B). The hrizntal bar in each plt indicates the time during which the retina was expsed t a full-field adapting light. Fllwing the expsure t the adapting light in nrmal Ringer there was a large, transient increase in the spt-annulus respnse rati. After the spt-annulus respnse rati had recvered t its B ~--I 2.5 ~, 2.0 I.-- O Q. Or) CURARE %... i..%.... LIGHT I I I TIME (rain) FIGURE 4. DTC des nt blck the uncupling effect f adapting light. (A) Effect f a 30 sec diffuse adapting light (intensity 9.7 lg Q) n spt-annulus respnse rati in nrmal Ringer. (B) Same as (A) but in the presence f 100/tM DTC. Secnd adapting light was 10 min after additin f DTC. Spt and annulus intensity, 9.1 lg Q. cntrl value 100 pm DTC was added t the superfusate. After 10 min in DTC, at which time the respnses had reached a steady level, the retina was expsed again t the same adapting light. The adapting light caused abut the same increase in spt-annulus respnse rati in the presence f DTC as it did in cntrl Ringer, indicating that blcking nictinic receptrs did nt reduce the ability f light t stimulate dpamine release and uncuple hrizntal cells. Similar results were seen in fur ther cells, each frm a different retina. The adapting light increased the spt-annulus respnse rati by a factr f in cntrl Ringer and by a factr f in the presence f 100 #M DTC (n = 5). A paired t-test indicated that the difference between the effect f the adapting light in the presence vs absence f DTC was nt significant (P = 0.44). Carbachl stimulates release f [ 3H ]dpamine Additinal evidence that the effect f carbachl n hrizntal cell cupling is via stimulatin f dpamine release was prvided by measuring its effect n the release f [3H]dpamine frm the retina. Dark-adapted retinas which had been preladed with [3H]dpamine were superfused with Ringer cntaining 2-20pM nmifensine t blck reuptake f released dpamine. As shwn in Fig. 5, the additin f 50/~M carbachl caused an increase in radiactivity in the superfusate. This was seen in nine f ten experiments. In mst cases the increase in radiactivity in respnse t carbachl was

5 CHOLINERGIC MODULATION IN MUDPUPPY RETINA 3937 t150 - t w looo N 9~ a. ~ ! L ,,,,,,, TIME (min) FIGURE 5. Carbachl stimulates release f [3H]dpamine frm the retina. Hrizntal bar indicates time when superfusate cntained 50 pm carbachl. abut 1/4 t 1/3 as great as the increase caused by 40 mm K. As a cntrl t ensure that the release was frm dpaminergic neurns rather than frm ther cells which may have taken up the label nnspecifically, 20 #M nmifensine was included in the incubatin medium in tw additinal experiments. When nmifensine was present during incubatin the backgrund release, retinal radiactivity and effect f 40 mm K were all very small, and carbachl did nt cause any detectable increase in radiactivity. DISCUSSION The finding that carbachl uncuples hrizntal cells and that this actin is blcked by dpamine antagnists suggests that ACh stimulates dpamine release in mudpuppy retina, as in fish and tiger salamander (Negishi & Drujan, 1979; Hare & Owen, 1995). The finding that carbachl als caused an increase in release f radiactivity frm retinas ]?reladed with [3H]dpamine prvides additinal evidence that the effect f carbachl n hrizntal cell cupling is due t stimulatin f dpamine release. When retinas were expsed t carbachl fr several minutes the uncupling effect n hrizntal cells usually increased t a maximum and then slwly declined, even in the cntinued presence f carbachl. This might be due t desensitizatin f ACh receptrs, since the uncupling effect f dpamine des; nt decline significantly with time (Dng & McReynlds, 1991). Hwever, the sensitivity t carbachl cmpletely recvered after a min washut in Ringer. The findings that the uncupling effect f carbachl n hrizntal cells was mimicked by nictinic but nt muscarinic agnists, and was blcked by the nictinic antagnist DTC indicate that it is mediated by nictinic but nt muscarinic receptrs. Furthermre, the fact that DTC did nt blck the ability f light t uncuple FIGURE 6. Pstulated light-evked and chlinergic inputs t dpaminergic amacrine cells in mudpuppy retina. Dpaminergic amacrine cells (DOP) are driven by n-center biplar cells (DB) in a sign-preserving manner. This is shwn as a dashed line since it is nt knwn if this is a mnsynaptic cnnectin. Synapses frm chlinergic neurns (ACh) nt dpaminergic amacrine cells are shwn as mnsynaptic, althugh this is nt certain. The chlinergic cells are nt part f the direct pathway between phtreceptrs (P) and dpaminergic cells. Dpamine released frm dpaminergic amacrine cells diffuses t hrizntal cells (HC). + and - signs indicate signpreserving and sign-inverting synapses, respectively. hrizntal cells indicates that chlinergic neurns are nt an essential part f the pathway by which light uncuples hrizntal cells. Figure 6 summarizes the light-evked and chlinergic inputs t the dpaminergic neurns in mudpuppy retina. Previus studies (Dng & McReynlds, 1991) shwed that the dpaminergic cells receive excitatry input frm the n-pathway. The chlinergic excitatry input t the dpaminergic cells is separate frm this pathway. The chlinergic input is shwn as directly nt dpaminergic cells, althugh this is nt certain. Althugh n chlinergic neurns have been specifically identified in mudpuppy retina, it is likely that they are a type f amacrine cell as in ther vertebrate retinas [reviewed in Massey & Redburn (1987); Hutchins (1987)]. Althugh it is nt yet knwn what factrs regulate the chlinergic input t dpaminergic neurns in the retina, the finding that DTC increased hrizntal cell cupling in dark-adapted retinas suggests that there was sme tnic, endgenus chlinergic stimulatin f dpaminergic cells under these cnditins. REFERENCES Baldridge, W. H. & Ball, A. K. (1991). Backgrund illuminatin reduces hrizntal cell receptive-field size in bth nrmal and 6- hydrxydpamine-lesined gldfish retinas. Visual Neurscience, 7, Baldridge, W. H., Jamiesn, M. S. & Ball, A. K. (1993). Rle f nitric xide in the cntrl f hrizntal cell receptive field size. Investigatins in Ophthalmlgy and Visual Science, 34, Batright, J. H., Hel, M. J. & Iuvne, P. M. (1989). Stimulatin f endgenus dpamine release and metablism in amphibian retina by light- and K -evked deplarizatin. Brain Research, 482, DeVries, S. H. & Schwartz, E. A. (1989). Mdulatin f an electrical synapse between slitary pairs f catfish hrizntal cells by

6 3938 K.L. MYHR and J. S. McREYNOLDS dpamine and secnd messengers. Jurnal f Physilgy, 414, Djamgz, M. B.A. & Wagner, H.-J. (1992). Lcalizatin and functin f dpamine in the adult vertebrate retina. Neurchemistry Internatinal, 20, Dng, C.-J. & McReynlds, J. S. (1991). The relatinship between light, dpamine release and hrizntal cell cupling in the mudpuppy retina. Jurnal f Physilgy, 440, Dng, C.-J. & McReynlds, J. S. (1992). Cmparisn f the effects f flickering and steady light n dpamine release and hrizntal cell cupling in the mudpuppy retina. Jurnal f Neurphysilgy, 67, Dwling, J. E. (1991). Retinal neurmdulatin: The rle f dpamine. Visual Neurscience, 7, Drujan, B. D., Salas, R., Laufer, M. & Urbina, M. (1990). Retinal neurtransmitter interactin as reflected in hrizntal cell spatial behaviur. Jurnal f Neural. Transmissin, 29 SuppL, Hare, W. A. & Owen, W. G. (1995). Similar effects f carbachl and dpamine n neurns in the distal retina f the tiger salamander. Visual Neurscience, 12, Hutchins, J. B. (1987). Acetylchline as a neurtransmitter in the vertebrate retina. Experimental Eye Research, 45, Kirsch, M. & Wagner, H.-J. (1989). Release pattern f endgenus dpamine in telest retina during light adaptatin and pharmaclgical stimulatin. Visin Research, 29, Lasater, E. M. & Dwling, J. E. (1985). Dpamine decreases cnductance f the electrical junctins between cultured retinal hrizntal cells. Prceedings f the Natinal Academy f Science USA, 82, Mangel, S. C. & Dwling, J. E. (1985). Respnsiveness and receptive field size f carp hrizntal cells are reduced by prlnged darkness and dpamine. Science, 229, Marshall, L. M. & Werblin, F. S. (1978). Synaptic transmissin t the hrizntal cells in the retina f the larval tiger salamander. Jurnal f Physilgy, 279, Massey, S. C. & Redburn, D. (1987). Transmitter circuits in the vertebrate retina. Prgress in Neurbilgy, 28, Mills, S. L. & Massey, S. C. (1993). L-arginine uncuples A-type hrizntal cells in rabbit retina. Investigatins in Ophthalmlgy and Visual Science, 34, Miyachi, E.-I., Murakami, M. & Nakaki, T. (1990). Arginine blcks gap junctins between retinal hrizntal cells. NeurReprt, 1, Myhr, K. L., Dng, C.-J. & McReynlds, J. S. (1994). Cnes cntribute t light-evked, dpamine-mediated uncupling f hrizntal cells in the mudpuppy retina. Jurnal f Neurphysilgy, 72, Negishi, K. & Drujan, B. D. (1979). Similarities in effects f acetylchline and dpamine n hrizntal cells in the fish retina. Jurnal f Neurscience Research, 4, Negishi, K., Teranishi, T. & Kat, S. (1990). The dpamine system f the telest fish retina. Prgress in Retinal Research, 9, Picclin, M., Neytn, J. & Gerschenfeld, H. M. (1984). Decrease f gap junctin permeability induced by dpamine and cyclic adensine 3':5'-mnphsphate in hrizntal cells f turtle retina. Jurnal f Neurscience, 4, Picclin, M., Neytn, J., Witkvsky, P. & Gerschenfeld, H. M. (1982). 7-Aminbutyric acid antagnists decrease junctinal cmmunicatin between hrizntal cells f the retina. Prceedings f the Natinal Academy f Science USA, 79, Rashid, K., Baldridge, W. H. & Ball, A. K. (1993). Evidence fr D2 receptr regulatin f dpamine release in the gldfish retina. Jurnal f Neurchemistry, 61, Teranishi, T., Negishi, K. & Kat, S. (1983). Dpamine mdulates S- ptential amplitude and dye-cupling between external hrizntal cells in carp retina. Nature, 301, Witkvsky, P. & Dearry, A. (1992). Functinal rles f dpamine in the vertebrate retina. Prgress in Retinal Research, 11, Acknwledgement--This wrk was supprted by NIH Research Grant EY01653 and Cre Grant EY07003.