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Mesostriatal projections from ventral tegmentum and dorsal raphe: Cells project ipsilaterally or contralaterally but not bilaterally
11
k
AND
( R ~ v e d May !Sth~ 1982; Revised version received 3une 21st, I982; Accepted June 22nd, 1982)
~ ¢ cei|s oforigin of the brainstem projection to the caudate-putamen (CP) were examined ia the albiac~ rat by the use of two fluorescent retrograde tracers. Nuclear yellow was injected into the CP of one kernisph~e and granular blue was injected imo the contralateral CP. Retrogradely labeled cells were The results VTA ~o the y projecting jpsilaterai!y CP. In DR, ells were oc, were interracy projee~A and DR.
T h e e f f e r e n t p r o j e c t i o n s f r o ~ t h e m e s e n c e p h a l i c m o n o a m i n e r":.clei to the caudate.putaraen (CP)are predominantly ipsiiateral. Coatra!ateral projecti)ns,
Fig. 1. |P.jection sites~ On cororffd section~ (A) and rt~edial (B) bilateral pairs o f Cypi~_~ spread o f dye in *he primary and f~eeondary zo~'~es, and the c~nnula traet is i n d i c ~
by a solid lin©,
anesthetized and Frozen sections c cleaned slides, a~ wavelength was 31 third :~ection thro Two control e~ the CP in one an~ another animal. I were visible in the resion of SN/VTA and DR. T h e ~ were readily distinguishable from retrogradely labeled cells.
Fig.2. Retrograde labeling in SN/VTA. The area indicated on the corona~ ~ction in A is shown enlarged in B. Onthe tracing oftbJs region in C, relevant and nearby structures are ~abeled. In addition, the typical diaribution of cells | a ~ l ~ in SN/TVA by b?,Zteral injections in medial Ci~ is shown. Open st~rs indicate teas labeled by the ipsilaterall injection, while the Larger, filled stars indicate cells labeled by the contralateral injection. In Ditbe distribution of cells labeled by injections into the latei'al CP is diagrammed. Abbreviadomi aon, medial iermhml nucleus of the accessory optic syszem; cp, cerebral pedu~ac e; dmn, deep me~ncephalic nuc~,eas; ml, medial ~emniscus; pint, posteroomammitlo-tegmental trivet; pn~ p~ranigraiis region of VTA; rd, red nucleus, me, substanfia nigra, pars compacta; snL substa~t a nigra, par~ lateralis; snr, ~ubstantia nigra, p~rs reticulata; llI, roots of oculomotor nerve.
report [6], the majority of cells labeled were located ipsilateral to the ~n~ectk,n site,
14
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, * *~r
l
\
/ /
Fig. 3. Retrograde abeling in DR. The ~tea ~ithin the box in A is enlarged it~ B. C ~ad D are iracings of the region ~urrounding the DR. Oper~ star~ indicale the cells labeled by the ipsilateral injection and ihe larger, filled stals indicate cell~ labeled by the comralateral injection. For greater clarity, results are diagrammed for one half of ~he brain only. Cells in C were labeled following a pair of media~ CP i~jecfions, ceils in D were labelea following lateral CP injections. Abbreviations: a, cerebral ~ , e d u c t ; be, brachium conjunctivum; mlf, medial longitudinal fascicnlus; omn, oculomotor nucleus; I:~g~ periaqueductal gray.
sensitive retrograde tracers [9]. The fact that no double-labeled cells were ob~rved following bilateral injections into CP, thus, suggests that SN/VTA and DK cells de not give rise to collaterals which branch to the ipsilaterat and contralateral CP, Rather, these data suggest that separate populations of cells in SN/VTA and DR project to ipsilateral or contra:a~eral CP. The existence of unilateral, topographically organized contralateral projections fl'om the~,e areas to the CP is of interest with regard to the so,called °prefron~a~ system'. Contratateral projections fror~ ~'refrontal cortex to the CP have previously been described in the monkey [2], and commisural CP t o C P projections have also been described [i]. This multiplicity of contralateral projections may have impor' tam effects in ~:he recovery of function following damage to these areas, as well as having a role in the normal |'unction of this system,
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i
15
A and Bare sections through the SN~VTA ipsilatera[ to a BG injection and comralmeral t~) a NY injection. In each one, one NY-labeled cell (indicated by the arrow) is visible in a field of GB-labeled cells. NY labels the nucleus a pale yellow, while GB labels the cytoplasm iight blue with light tranules. C is a section through the VTA, ipsilateral to a GB injection. One ceil is indicated which contains NY while the others contain GB. D is from a section through DR, ipsilateral ¢o a NY injection. One cell (arrow) is labeled with GB.
Unilateral injections of amphetamine or ¢x-methy~-p-tyrosine into SN/VTA, as well as unilateral paw stimulation, have been shown to affect dopamine release in striatum. Interestinglty, changes in the contralateral striatam were always opposite to those ob~rved in the ipsi|ateral striatum [8]. It is possible that the contrataterally projecting SN/VTA cells we have described are involved in the effects observed in contralateral CP. The observation that contralateral projections arise frora different cells than ipsilateral projections is ccnsistent with the quantitatively opposite effects on dopandne turnover observed contralateral to SN/VTA manipulations. It is not clear from our data, however, whether these eontralaterally projecting cells arc dopaminergic. Studies combining the use of retrograde tracers with the demonstration of ca~echolamine flu ~rescence are in progress to examine this issue. The development of the DR n~clei have been described [7]. These ceils arise as two ce|l groups at the lateral borders of the fourth ventricle and migrate ventrally. They then, in a second migration, move medialb' to their midiine position. The tmpulation of contrala~eratly projecting cei|s we have observed in D~ may thu~,; represent ipsilateraIIy projecting cells which have 'over'migrated ~ across ~t:e midli~eo
16
Res. Bull., in press. 5 Fass, B.B. end Butcher, L.L. Evidence for a c r o ~ d ~igrt~triatal pat~:way inrats, Nm~ro~d. Le~L, 22 (1981) lrlg-tl3, 6 Jacobs, B.L., Foote, S.L° and Bloom, F.E., Differenti~ projections ~f nettrom witMa the dor~| raphe nuct,us of the ca~: a horseradish pcroxida~ ~[HRP) study, Brail~ Re~i, 147 (1975).149~[53, 7 Levitt, P. and ~,'~oor,LR To, Drvelopmenta| organization of raphe 5erot(min neuron groups in ~he rat, Anal Embryol., 15¢ (1978) 241-25~. 8 Nieoullon, A., C.he~'am~, A. a~d Glowinski, J., lnterd,pendence of ,l,e nigrostriatM dopaminergi¢ systems on Lhe two ~ide~ of lhe brain in the cat, Science, 198 (1977) 4i6-418. 9 Sawchcmko, P.E. ant:
|0 Simon, H . Le MoaL smdi~l after iota! i~,~j!
k
AND
( R ~ v e d May !Sth~ 1982; Revised version received 3une 21st, I982; Accepted June 22nd, 1982)
~ ¢ cei|s oforigin of the brainstem projection to the caudate-putamen (CP) were examined ia the albiac~ rat by the use of two fluorescent retrograde tracers. Nuclear yellow was injected into the CP of one kernisph~e and granular blue was injected imo the contralateral CP. Retrogradely labeled cells were The results VTA ~o the y projecting jpsilaterai!y CP. In DR, ells were oc, were interracy projee~A and DR.
T h e e f f e r e n t p r o j e c t i o n s f r o ~ t h e m e s e n c e p h a l i c m o n o a m i n e r":.clei to the caudate.putaraen (CP)are predominantly ipsiiateral. Coatra!ateral projecti)ns,
Fig. 1. |P.jection sites~ On cororffd section~ (A) and rt~edial (B) bilateral pairs o f Cypi~_~ spread o f dye in *he primary and f~eeondary zo~'~es, and the c~nnula traet is i n d i c ~
by a solid lin©,
anesthetized and Frozen sections c cleaned slides, a~ wavelength was 31 third :~ection thro Two control e~ the CP in one an~ another animal. I were visible in the resion of SN/VTA and DR. T h e ~ were readily distinguishable from retrogradely labeled cells.
Fig.2. Retrograde labeling in SN/VTA. The area indicated on the corona~ ~ction in A is shown enlarged in B. Onthe tracing oftbJs region in C, relevant and nearby structures are ~abeled. In addition, the typical diaribution of cells | a ~ l ~ in SN/TVA by b?,Zteral injections in medial Ci~ is shown. Open st~rs indicate teas labeled by the ipsilaterall injection, while the Larger, filled stars indicate cells labeled by the contralateral injection. In Ditbe distribution of cells labeled by injections into the latei'al CP is diagrammed. Abbreviadomi aon, medial iermhml nucleus of the accessory optic syszem; cp, cerebral pedu~ac e; dmn, deep me~ncephalic nuc~,eas; ml, medial ~emniscus; pint, posteroomammitlo-tegmental trivet; pn~ p~ranigraiis region of VTA; rd, red nucleus, me, substanfia nigra, pars compacta; snL substa~t a nigra, par~ lateralis; snr, ~ubstantia nigra, p~rs reticulata; llI, roots of oculomotor nerve.
report [6], the majority of cells labeled were located ipsilateral to the ~n~ectk,n site,
14
,\ ~:zg X ",,
, * *~r
l
\
/ /
Fig. 3. Retrograde abeling in DR. The ~tea ~ithin the box in A is enlarged it~ B. C ~ad D are iracings of the region ~urrounding the DR. Oper~ star~ indicale the cells labeled by the ipsilateral injection and ihe larger, filled stals indicate cell~ labeled by the comralateral injection. For greater clarity, results are diagrammed for one half of ~he brain only. Cells in C were labeled following a pair of media~ CP i~jecfions, ceils in D were labelea following lateral CP injections. Abbreviations: a, cerebral ~ , e d u c t ; be, brachium conjunctivum; mlf, medial longitudinal fascicnlus; omn, oculomotor nucleus; I:~g~ periaqueductal gray.
sensitive retrograde tracers [9]. The fact that no double-labeled cells were ob~rved following bilateral injections into CP, thus, suggests that SN/VTA and DK cells de not give rise to collaterals which branch to the ipsilaterat and contralateral CP, Rather, these data suggest that separate populations of cells in SN/VTA and DR project to ipsilateral or contra:a~eral CP. The existence of unilateral, topographically organized contralateral projections fl'om the~,e areas to the CP is of interest with regard to the so,called °prefron~a~ system'. Contratateral projections fror~ ~'refrontal cortex to the CP have previously been described in the monkey [2], and commisural CP t o C P projections have also been described [i]. This multiplicity of contralateral projections may have impor' tam effects in ~:he recovery of function following damage to these areas, as well as having a role in the normal |'unction of this system,
( i l
¸¸
i
i
15
A and Bare sections through the SN~VTA ipsilatera[ to a BG injection and comralmeral t~) a NY injection. In each one, one NY-labeled cell (indicated by the arrow) is visible in a field of GB-labeled cells. NY labels the nucleus a pale yellow, while GB labels the cytoplasm iight blue with light tranules. C is a section through the VTA, ipsilateral to a GB injection. One ceil is indicated which contains NY while the others contain GB. D is from a section through DR, ipsilateral ¢o a NY injection. One cell (arrow) is labeled with GB.
Unilateral injections of amphetamine or ¢x-methy~-p-tyrosine into SN/VTA, as well as unilateral paw stimulation, have been shown to affect dopamine release in striatum. Interestinglty, changes in the contralateral striatam were always opposite to those ob~rved in the ipsi|ateral striatum [8]. It is possible that the contrataterally projecting SN/VTA cells we have described are involved in the effects observed in contralateral CP. The observation that contralateral projections arise frora different cells than ipsilateral projections is ccnsistent with the quantitatively opposite effects on dopandne turnover observed contralateral to SN/VTA manipulations. It is not clear from our data, however, whether these eontralaterally projecting cells arc dopaminergic. Studies combining the use of retrograde tracers with the demonstration of ca~echolamine flu ~rescence are in progress to examine this issue. The development of the DR n~clei have been described [7]. These ceils arise as two ce|l groups at the lateral borders of the fourth ventricle and migrate ventrally. They then, in a second migration, move medialb' to their midiine position. The tmpulation of contrala~eratly projecting cei|s we have observed in D~ may thu~,; represent ipsilateraIIy projecting cells which have 'over'migrated ~ across ~t:e midli~eo
16
Res. Bull., in press. 5 Fass, B.B. end Butcher, L.L. Evidence for a c r o ~ d ~igrt~triatal pat~:way inrats, Nm~ro~d. Le~L, 22 (1981) lrlg-tl3, 6 Jacobs, B.L., Foote, S.L° and Bloom, F.E., Differenti~ projections ~f nettrom witMa the dor~| raphe nuct,us of the ca~: a horseradish pcroxida~ ~[HRP) study, Brail~ Re~i, 147 (1975).149~[53, 7 Levitt, P. and ~,'~oor,LR To, Drvelopmenta| organization of raphe 5erot(min neuron groups in ~he rat, Anal Embryol., 15¢ (1978) 241-25~. 8 Nieoullon, A., C.he~'am~, A. a~d Glowinski, J., lnterd,pendence of ,l,e nigrostriatM dopaminergi¢ systems on Lhe two ~ide~ of lhe brain in the cat, Science, 198 (1977) 4i6-418. 9 Sawchcmko, P.E. ant:
|0 Simon, H . Le MoaL smdi~l after iota! i~,~j!