Epilepsia, 33(5):785-788, 1992 Raven Press, Ltd., New York 0 International League Against Epilepsy
Monaural Audiogenic Seizures: Evidence for Control by Parallel Processes Howard M. Reid and Robert L. Collins Department of Psychology, State University College at Buffalo, Buffalo, New York; and The Jackson Laboratory, Bar Harbor, Maine, U . S . A .
Summary: SJL/J mice were binaurally sensitized and monaurally tested for susceptibility to sound-induced seizure. Most control subjects exhibited the expected biphasic pattern of running. In mice in the experimental groups, the acoustic stimulation was interrupted for 0.05). Duration of the acoustic time-out periods were similar for groups 3 and 4 and groups 5 and 6 (15.8 vs. 17.6 s). Seizure progression for mice in groups 3 and 4 did not differ from that of the control mice (series of F tests, all p > 0.05). Seizure progressions for mice of groups 5 and 6 differed markedly from
those of the control mice, however (Tables 1 and 2). Although no control mouse had more than two bursts of running preceding onset of clonus, 9 of the 10 mice in groups 5 and 6 exhibited a triphasic pattern of running (chi-square = 22.95, p < 0.0001). The one mouse in group 5 (first right then left ear blocked) that had a biphasic pattern of running was also the only mouse in the experiment that did not fall on the side of the blocked ear during clonus. Accordingly, we concluded that the glycerine block was ineffective and that this mouse was functionally a group 3 animal. Finally, the biphasic seizure progressions that followed the reintroduction of sound in the 9 mice with a triphasic pattern from groups 5 and 6 were compared with the biphasic progressions exhibited by control mice (groups 1 and 2) and those assigned to groups 3 and 4 (Fig. 1). We noted no differences in latencies to any stage of biphasic seizure activity (series of F tests, all with p > 0.05, Fig. 1). DISCUSSION The biphasic seizure progressions of monaurally tested mice did not differ as a result of the side of ear block. This confirms our earlier observations that the side of monaural test did not affect latencies to running or clonus (Reid and Collins, 1989). This finding suggests that either a single process controls seizure progression regardless of the side of acoustic stimulation or that two lateralized but identical processes are involved. The data from mice assigned to groups 5 and 6 were used to distinguish between these alternatives. These mice had the side of ear block switched immediately after the end of the initial episode of running. If a single process controls biphasic seizure progression, this manipulation should have no effect. Alternatively, if the biphasic seizure progression is controlled by lateralized processes, these mice should have undergone an additional biphasic seizure after reintroduction of the acoustic stimulation. The results were clear. Nine of the 10 mice in groups 5 and 6 exhibited a triphasic pattern of running. The biphasic pattern after sound was reintroduced was indistinguishable from that exhibited by
TABLE 2. Latencies in seconds to progressive stages of audiogenic seizure activity Experimental condition
n
Run 1 start
Run 1 stop
Bell reenergized
Run 2 start
Run 2 stop
Run 3 start
Fall
Recovery
Control Interruption Reversal
17 10 9"
9.7 (3.3) 8.3 (2.7) 9.7 (2.8)
14.6 (3) 13.9 (2.3) 15.2 (2.9)
29.7 (2.2) 32.8 (3.8)
37.9 (5.5) 38.9 (3.3) 42.9 (6.4)
48.6 (6.4)
68.6 (5.7)
45.7 (4.3) 47.3 (4.2) 76.7 (7)
63.4 (18.4) 58.9 (4.2) 88.3 (7.2)
Values are mean f SD. Mice with a triphasic seizure pattern.
a
W e p s i a , Vol. 33, No. 5 , 1992
787
MONAURAL AUDIOGENIC SEIZURES
Sciences Grant from the State University College of New York at Buffalo. The Jackson Laboratory is fully accredited by the American Association for Accreditation of Laboratory Animal Care.
70 60
REFERENCES
50
c0:
Fuller JL, Collins RL. Temporal parameters of sensitization for audiogenic seizures in SJL/J mice. Dev Psychobid 1968a;l:
Q)
2
40
185-8.
>.
0
5I5
30 20 10
0
BlPHASlC AUDIOGENIC SEIZURE FIG. 1. Mean latencies to progressive stages of biphasic audiogenic seizure in SJUJ mice tested monaurally. Mice in the control groups (open bars) received continuous monaural stimulation. Those in the interrupt groups (solid bars) had acoustic stimulation turned off for not more than 20 s at the conclusion of the first run. Mice in the reversal groups (hatched bars) were treated similarly except that the side of ear block was reversed at the conclusion of the first run. The biphasic seizure progression that followed this reversal did not differ from the biphasic progressions exhibited by control or interrupt mice.
control mice (groups 1 and 2). This outcome did not result simply from having had acoustic stimulation interrupted because mice in groups 3 and 4 did not exhibit the triphasic pattern. Therefore, biphasic AGS progressions evidently are the result of lateralized processes. The locus of these processes is probably at the level of the inferior colliculus (IC). Bilateral destruction of the 1C abolishes AGS susceptibility (Wada et al., 1970), whereas infusion of excitant amino acids into the IC enhances AGS risk (Millan et al., 1986). In contrast, lesions of the more rostra1 superior colliculus and medial geniculate body affect progression to clonic and tonic stages but not wild-running activity (Willott and Lu, 1980), and hippocampal lesions increase susceptibility and shorten latency to AGS in rats (Kim and Kim, 1962), and mice (Reid et al., 1983a, 19836). Furthermore, the effect of lesioning the IC is itself lateralized; AGS susceptibility is prevented only when the side of lesion is contralateral to the ear acoustically stimulated (Ward, 1971). Acknowledgment: This work was supported by NIH Grant No. GM 23618 and a Faculty of Natural and Social
Fuller JL, Collins RL. Mice unilaterally sensitized for audiogenic seizures. Science 1968b;162:1295. Kim C, Kim CU. Effect of hippocampal ablation on audiogenic seizures in rats. J Comp Physiol Psycho/ 1962;55:288-92. Millan MH, Meldrum BS, Faingold CL. Induction of audiogenic seizure susceptibility by focal infusion of excitant amino acid or bicuculline into the inferior colliculus of normal rats. Exp Neurol 1986;91:634-9. Reid HM, Bowler KJ, Weiss C. Hippocampal lesions increase the severity of unilaterally induced audiogenic seizures and decrease their latency. E.xp Neurol 1983a;81:240-4. Reid HM, Collins RL. Audiogenic seizures in mice: asymmetries of the preconvulsive running pattern and subsequent seizure. Anim Leurn Behav 1982;10:321-4. Reid HM, Collins RL. Lateralized audiogenic seizure: motor asymmetries exhibited and the effects of interrupted stimulation. Behuv Neural Biol 1986;46:424-31. Reid HM, Collins RL. Monaural and binaural audiogenic seizures in mice. Behav Neural Biol 1989;51:136-44. Reid HM, Mamott BD, Bowler KJ. Hippocampal lesions render SJL/J mice susceptible to audiogenic seizures. Exp Neurol 1983b ;82:23740.
Wada JA, Terao A, White B, Jung E. Inferior colliculus lesion and audiogenic seizure susceptibility. Exp Neurol 1970;28: 326-32.
Ward R. Unilateral susceptibility to audiogenic seizure impaired by contralateral lesions in the inferior colliculus. Exp Neurol 1971;32:313-16.
Willott JF, Lu SM. Midbrain pathways of audiogenic seizures in DBAI2 mice. Exp Neurol 1980;70:288-99.
R~SUME Des souris SJL/J ont Cte sensibilistes de facon biauriculaire et testees de facon monoauriculaire pour leur susceptibilite aux crises induites par les sons. La plupart des sujets contr6le ont manifestC le comportement biphasique attendu de course. Les souris des groupes experimentaux ont beneficiC d’une interruption de la stimulation acoustique pendant moins de 20 secondes apres la fin de l’tpisode de course initiale. Pendant cette pkriode de calme, le cBt6 de l’oreille bloqute a CtB changt pour quelques souris. Pour ces animaux, une crise biphasique indtpendante est survenue lorsque la stimulation acoustique Ctait rkintroduite. Ceci indique que la progression biphasique caracteristique des crises apres stimulation monauriculaire est le resultat d’un processus lattralise. Les auteurs concluent que le lieu de ce processus est vraisemblablement au niveau du colliculus inferieur . (P. Genton, Marseille)
RESUMEN Para determinar la susceptibilidad a ataques inducidos por el sonido se han estudiado mono-auditivamente ratones SJL/J previamente sensibilizados bi-auditivamente. La mayor parte de 10s sujetos control rnostraron el habitual patr6n bifasico de carrera. En 10s ratones del grupo experimental se interrumpid la estimulacidn acustica durante menos de 20 segundos a1 terminar el brote inicial de carrera. Durante este period0 sin estimulo, en algunos ratones se cambi6 el oido bloqueado. En estos sujetos un ataque bifasico independiente se observ6 cuando la estimulaci6n Epilepsia, Vol. 33, No. 5 , 1992
788
H . M . REID AND R . L . COLLINS
acustica se reproducia. Este dato indica que la progresi6n biffisica del ataque, caracteristica de 10s test monoauditivos es el resultado de un proceso lateralizado. Los autores concluyen que este proceso, probablemente, se localiza a nivel del coliculo inferior. (A. Portera-SAnchez, Madrid)
ZUSAMMENFASSUNG SILII Mause wurden biaurikular gereizt und monaurikular auf gerausch-induzierte Anfallsempfindlichkeit getestet. Die meisten Kontrolltiere zeigten das erwartete biphasische Laufmuster. Bei
Epilepsia, Voi. 33, N o . 5 , 1992
Mausen der Untersuchungsgruppe wurde die akustische Stimulation fur weniger als 20 Sekunden am Ende des ersten Laufmusters unterbrochen. Wahrend dieser Ruheperiode wurde bei einigen Mausen die Seite des geblockten Ohrs gewechselt. Bei diesen Tieren trat bei Wiedereinsetzen der akustischen Stimulation ein unabhangiger biphasischer Anfall auf. Dies zeigt, da13 die bei monotischer Testung ypische biphasische Anfallsausbreitung Ergebnis eines lateralisierten Prozesses ist. Daraus schlieBen wir, daB der Ort dieses Geschehns wahrscheinlich in Hohe des Colliculus inferior liegt. (C. G. Lipinski, HeidelberglNeckarg.emun~
Monaural Audiogenic Seizures: Evidence for Control by Parallel Processes Howard M. Reid and Robert L. Collins Department of Psychology, State University College at Buffalo, Buffalo, New York; and The Jackson Laboratory, Bar Harbor, Maine, U . S . A .
Summary: SJL/J mice were binaurally sensitized and monaurally tested for susceptibility to sound-induced seizure. Most control subjects exhibited the expected biphasic pattern of running. In mice in the experimental groups, the acoustic stimulation was interrupted for 0.05). Duration of the acoustic time-out periods were similar for groups 3 and 4 and groups 5 and 6 (15.8 vs. 17.6 s). Seizure progression for mice in groups 3 and 4 did not differ from that of the control mice (series of F tests, all p > 0.05). Seizure progressions for mice of groups 5 and 6 differed markedly from
those of the control mice, however (Tables 1 and 2). Although no control mouse had more than two bursts of running preceding onset of clonus, 9 of the 10 mice in groups 5 and 6 exhibited a triphasic pattern of running (chi-square = 22.95, p < 0.0001). The one mouse in group 5 (first right then left ear blocked) that had a biphasic pattern of running was also the only mouse in the experiment that did not fall on the side of the blocked ear during clonus. Accordingly, we concluded that the glycerine block was ineffective and that this mouse was functionally a group 3 animal. Finally, the biphasic seizure progressions that followed the reintroduction of sound in the 9 mice with a triphasic pattern from groups 5 and 6 were compared with the biphasic progressions exhibited by control mice (groups 1 and 2) and those assigned to groups 3 and 4 (Fig. 1). We noted no differences in latencies to any stage of biphasic seizure activity (series of F tests, all with p > 0.05, Fig. 1). DISCUSSION The biphasic seizure progressions of monaurally tested mice did not differ as a result of the side of ear block. This confirms our earlier observations that the side of monaural test did not affect latencies to running or clonus (Reid and Collins, 1989). This finding suggests that either a single process controls seizure progression regardless of the side of acoustic stimulation or that two lateralized but identical processes are involved. The data from mice assigned to groups 5 and 6 were used to distinguish between these alternatives. These mice had the side of ear block switched immediately after the end of the initial episode of running. If a single process controls biphasic seizure progression, this manipulation should have no effect. Alternatively, if the biphasic seizure progression is controlled by lateralized processes, these mice should have undergone an additional biphasic seizure after reintroduction of the acoustic stimulation. The results were clear. Nine of the 10 mice in groups 5 and 6 exhibited a triphasic pattern of running. The biphasic pattern after sound was reintroduced was indistinguishable from that exhibited by
TABLE 2. Latencies in seconds to progressive stages of audiogenic seizure activity Experimental condition
n
Run 1 start
Run 1 stop
Bell reenergized
Run 2 start
Run 2 stop
Run 3 start
Fall
Recovery
Control Interruption Reversal
17 10 9"
9.7 (3.3) 8.3 (2.7) 9.7 (2.8)
14.6 (3) 13.9 (2.3) 15.2 (2.9)
29.7 (2.2) 32.8 (3.8)
37.9 (5.5) 38.9 (3.3) 42.9 (6.4)
48.6 (6.4)
68.6 (5.7)
45.7 (4.3) 47.3 (4.2) 76.7 (7)
63.4 (18.4) 58.9 (4.2) 88.3 (7.2)
Values are mean f SD. Mice with a triphasic seizure pattern.
a
W e p s i a , Vol. 33, No. 5 , 1992
787
MONAURAL AUDIOGENIC SEIZURES
Sciences Grant from the State University College of New York at Buffalo. The Jackson Laboratory is fully accredited by the American Association for Accreditation of Laboratory Animal Care.
70 60
REFERENCES
50
c0:
Fuller JL, Collins RL. Temporal parameters of sensitization for audiogenic seizures in SJL/J mice. Dev Psychobid 1968a;l:
Q)
2
40
185-8.
>.
0
5I5
30 20 10
0
BlPHASlC AUDIOGENIC SEIZURE FIG. 1. Mean latencies to progressive stages of biphasic audiogenic seizure in SJUJ mice tested monaurally. Mice in the control groups (open bars) received continuous monaural stimulation. Those in the interrupt groups (solid bars) had acoustic stimulation turned off for not more than 20 s at the conclusion of the first run. Mice in the reversal groups (hatched bars) were treated similarly except that the side of ear block was reversed at the conclusion of the first run. The biphasic seizure progression that followed this reversal did not differ from the biphasic progressions exhibited by control or interrupt mice.
control mice (groups 1 and 2). This outcome did not result simply from having had acoustic stimulation interrupted because mice in groups 3 and 4 did not exhibit the triphasic pattern. Therefore, biphasic AGS progressions evidently are the result of lateralized processes. The locus of these processes is probably at the level of the inferior colliculus (IC). Bilateral destruction of the 1C abolishes AGS susceptibility (Wada et al., 1970), whereas infusion of excitant amino acids into the IC enhances AGS risk (Millan et al., 1986). In contrast, lesions of the more rostra1 superior colliculus and medial geniculate body affect progression to clonic and tonic stages but not wild-running activity (Willott and Lu, 1980), and hippocampal lesions increase susceptibility and shorten latency to AGS in rats (Kim and Kim, 1962), and mice (Reid et al., 1983a, 19836). Furthermore, the effect of lesioning the IC is itself lateralized; AGS susceptibility is prevented only when the side of lesion is contralateral to the ear acoustically stimulated (Ward, 1971). Acknowledgment: This work was supported by NIH Grant No. GM 23618 and a Faculty of Natural and Social
Fuller JL, Collins RL. Mice unilaterally sensitized for audiogenic seizures. Science 1968b;162:1295. Kim C, Kim CU. Effect of hippocampal ablation on audiogenic seizures in rats. J Comp Physiol Psycho/ 1962;55:288-92. Millan MH, Meldrum BS, Faingold CL. Induction of audiogenic seizure susceptibility by focal infusion of excitant amino acid or bicuculline into the inferior colliculus of normal rats. Exp Neurol 1986;91:634-9. Reid HM, Bowler KJ, Weiss C. Hippocampal lesions increase the severity of unilaterally induced audiogenic seizures and decrease their latency. E.xp Neurol 1983a;81:240-4. Reid HM, Collins RL. Audiogenic seizures in mice: asymmetries of the preconvulsive running pattern and subsequent seizure. Anim Leurn Behav 1982;10:321-4. Reid HM, Collins RL. Lateralized audiogenic seizure: motor asymmetries exhibited and the effects of interrupted stimulation. Behuv Neural Biol 1986;46:424-31. Reid HM, Collins RL. Monaural and binaural audiogenic seizures in mice. Behav Neural Biol 1989;51:136-44. Reid HM, Mamott BD, Bowler KJ. Hippocampal lesions render SJL/J mice susceptible to audiogenic seizures. Exp Neurol 1983b ;82:23740.
Wada JA, Terao A, White B, Jung E. Inferior colliculus lesion and audiogenic seizure susceptibility. Exp Neurol 1970;28: 326-32.
Ward R. Unilateral susceptibility to audiogenic seizure impaired by contralateral lesions in the inferior colliculus. Exp Neurol 1971;32:313-16.
Willott JF, Lu SM. Midbrain pathways of audiogenic seizures in DBAI2 mice. Exp Neurol 1980;70:288-99.
R~SUME Des souris SJL/J ont Cte sensibilistes de facon biauriculaire et testees de facon monoauriculaire pour leur susceptibilite aux crises induites par les sons. La plupart des sujets contr6le ont manifestC le comportement biphasique attendu de course. Les souris des groupes experimentaux ont beneficiC d’une interruption de la stimulation acoustique pendant moins de 20 secondes apres la fin de l’tpisode de course initiale. Pendant cette pkriode de calme, le cBt6 de l’oreille bloqute a CtB changt pour quelques souris. Pour ces animaux, une crise biphasique indtpendante est survenue lorsque la stimulation acoustique Ctait rkintroduite. Ceci indique que la progression biphasique caracteristique des crises apres stimulation monauriculaire est le resultat d’un processus lattralise. Les auteurs concluent que le lieu de ce processus est vraisemblablement au niveau du colliculus inferieur . (P. Genton, Marseille)
RESUMEN Para determinar la susceptibilidad a ataques inducidos por el sonido se han estudiado mono-auditivamente ratones SJL/J previamente sensibilizados bi-auditivamente. La mayor parte de 10s sujetos control rnostraron el habitual patr6n bifasico de carrera. En 10s ratones del grupo experimental se interrumpid la estimulacidn acustica durante menos de 20 segundos a1 terminar el brote inicial de carrera. Durante este period0 sin estimulo, en algunos ratones se cambi6 el oido bloqueado. En estos sujetos un ataque bifasico independiente se observ6 cuando la estimulaci6n Epilepsia, Vol. 33, No. 5 , 1992
788
H . M . REID AND R . L . COLLINS
acustica se reproducia. Este dato indica que la progresi6n biffisica del ataque, caracteristica de 10s test monoauditivos es el resultado de un proceso lateralizado. Los autores concluyen que este proceso, probablemente, se localiza a nivel del coliculo inferior. (A. Portera-SAnchez, Madrid)
ZUSAMMENFASSUNG SILII Mause wurden biaurikular gereizt und monaurikular auf gerausch-induzierte Anfallsempfindlichkeit getestet. Die meisten Kontrolltiere zeigten das erwartete biphasische Laufmuster. Bei
Epilepsia, Voi. 33, N o . 5 , 1992
Mausen der Untersuchungsgruppe wurde die akustische Stimulation fur weniger als 20 Sekunden am Ende des ersten Laufmusters unterbrochen. Wahrend dieser Ruheperiode wurde bei einigen Mausen die Seite des geblockten Ohrs gewechselt. Bei diesen Tieren trat bei Wiedereinsetzen der akustischen Stimulation ein unabhangiger biphasischer Anfall auf. Dies zeigt, da13 die bei monotischer Testung ypische biphasische Anfallsausbreitung Ergebnis eines lateralisierten Prozesses ist. Daraus schlieBen wir, daB der Ort dieses Geschehns wahrscheinlich in Hohe des Colliculus inferior liegt. (C. G. Lipinski, HeidelberglNeckarg.emun~
