EFFECTS OF STIMULATING THE MIDBRAIN CENTRAL GRAY MATTER ON NEURONAL

RESPONSE IN THE CAT VENTROPOSTEROMEDIAL THALAMIC NUCLEUS

E. V. Gura and V. V. Garkavenko UDC 612.826.5:612.826.1

The effects of stimulating the midbrain central gray matter (CGM) on neuronal response in the ventroposteromedial (VPM) nucleus produced by stimulating tooth pulp, A-alpha and A-delta fibers of the intraorbital nerve and the caudal nu- cleus of the spinal trigeminal tract (CN STT) were investigated during experi- ments on cats under thiopental-chloralose anesthesia. It was found that apply- ing trains of stimuli to the CGM produced excitatory responses in a proportion of the test neurons with latencies of up to 30 msec. Application of condition- ing stimulus to the CGM led to suppression of response of efferent stimulation in neurons belonging to "low-threshold," "convergent," and "high-threshold" groups. Responses produced in 40% of neurons by stimulating tooth pulp and A- delta fibers of the suborbital nerve, as well as those evoked in 26.4% of tha- lamic VPMcells by stimulating A-alpha fibers of the suborbital nerve were com- pletely suppressed. The inhibitory effect found when stimulating CGM on re- sponse in certain neurons, produced by stimulating both the peripheral nerve and the CNSTT, would indicate that the CGM could exert an influence on the activity of thalamic VPM neurons directly.

INTRODUCTION

Stimulation of the midbrain central gray matter (CGM) has been found to exert a modulat- ing effect on sensory neurons of the medulla and spinal cord, suppressing for the most part responses produced by nociceptive stimuli [8, 9]. Morphological research has revealed ascend- ing projections from the CGM to the thalamic medial and ventrobasal complex nuclei [10-12], although information on influences from the CGM on thalamic neurons is only limited. Stimu- lating the CGM is known to inhibit its spontaneous and evoked activity in neurons of the ventroposterolateral and posterolateral thalamic nuclei [13] while leading to depression of response produced by nociceptive (and in just a proportion of the neurons to non-noxious) stimuli in neurons of the nonspecific thalamic medial nuclei.

Since neurons were found in the thalamic ventroposteromedial nucleus (VPM) responding to nociceptive afferents (here, tooth pulp) of the trigeminal nerve [2, 15, 16], it appeared worthwhile to investigate the effects of CGM stimulation on activity evoked in VPM neurons by stimulating both high-threshold afferent nociceptive fibers of the A-delta and C groups, and low-threshold non-nociceptive fibers belonging to the A-alpha group of the trigeminal nerve.

METHODS

Experiments were performed on cats weighing between 2.5 and 3.7 kg, anesthetized using 30 mg/kg sodium thiopental and 40 mg/kg alpha chloralose (i.p.).

Surgical procedures applied to the animals consisted of tracheotomy, catheterizing the femoral artery so as to measure blood pressure, catheterizing the forearm subcutaneous vein, situating bipolar stimulating electrodes on the pulp of the right and left canines, severing the suborbital nerve and applying to it a bipolar stimulating electrode. Having extracted the occipital portion of the right cerebral hemisphere by means of an electrode placed on the fibers approaching the Gasserian ganglia, we recorded the afferent wave arising as a result of stimulating the infraorbital nerve. Techniques of recording afferent waves and determining stimulation thresholds of the suborbital nerve have been described in our prevJ-

A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 20, No. 5, pp. 688-694, September-October, 1988. Original article submitted September 22, 1987.

508 0090-2977/88/2005-0508512.50 �9 1989 Plenum Publishing Corporation

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Ai,6 A~06

Fig. i. Location of stimulation sites of the midbrain central gray matter (dots). Frontal sections [7] shown below sketches of brain slices; PAG) central gray matter; SCS) superior colliculus; FTC) central tegmental field; ~) red nucleus; MGP) medial geniculate body; P) pyramidal tract; MLB) medial longitudinal bundle; NT) trochlear nerve nucleus.

a b

Pc v _ Ii

cGM + Pc

c ~ sN (2,o)

J

J ~ PC

mv ,q , - - ,

i I ZO ~ec ., L. ~Q. 105m v

fO msec

c SN(J,O) PI " - - I - ---r-T- -'---T- ,---r-r-

,CGM J,2QO ~ ) CGM (200 UA) + PI + SN ( 3 . 0 )

+ SN ( 3 . 0 ) C ~ ( I g ~ + PI

-' ~ :'--~-'~_be5 ~v fO msec

Fig. 2. Effects of stimulating midbrain central gray matter on response in "low-threshold" (a), "high-threshold" (b), and "convergent" (c) neurons of the ventroposteromedial thalamic nucleus induced by stimulating tooth pulp and the suborbital nerve; SN) suborbital nerve (stimulation intensity as a multiple of threshold level shown in brackets); CGM) midbrain central gray matter (level of stimulating current shown in brackets, ~A); PC) pulp of contralateral and PI) ipsilateral side.

ous study [5]. Low threshold fibers of the A-alpha group were found to be excited by stimula- tion of the infraorbital nerve at an intensity of i-4 thresholds but when this was intensified to nine thresholds, fibers of the A-delta group were also activated.

The caudal nucleus of the spinal trigeminal tract (CN STT) was stimulated by square- wave bursts of current (0.1-0.2 msec; 80-120 ~A) using uni- or bipolar nichrome electrodes spaced 250 ~m apart and inserted into the nucleus at obex level or 1-3 mm caudally to that site. Trains of 6-9 square-waves stimuli (0.2 msec; 100-200 ~A; 200-250 Hz) were used to stimulate the CGM. The electrode was implanted into the CGM in accordance with the coordi- nates of a stereotaxic atlas [7]. Methods of obtaining access to the thalamus and recording the activity of VPM neurons have been described in one of our previous publications [2].

Animals were immobilized by 0.01 mg/kg arduan i.v. during recording of thalamic neuronal activity and they were artificially ventilated. Activity was recorded from VPM neurons by means of glass microelectrodes filled with 4 M NaCI solution. Locations of recording and stimulating electrodes were determined by coagulation sites [i, 2] on i00 ~m serial brain slices prepared in a freezing microtome.

509

a CGM (130 msec) b SN {J,m ~ ) SNP.m P T

----C- "---"F- Jl -- CGM (80 msec) + SN (3.0) - ' ) ~ CGM +SN (3.0) CGM + PI

29 msec 2D msec

Fig. 3. Facilitatory effects of applying conditioned stimulus of midbrain central gray matter (CGM) on two "low-threshold" (a) and "convergent" (b) neurons of the thalamic ventroposteromedial nucleus recorded simultaneously and induced by stimulating tooth pulp and the suborbital nerve. Intervals between applying conditioned and test stimuli to the CGM shown in brack- ets (msec). Remaining notations as for Fig. 2.

RESULTS

The effects of stimulating CGM sites located within sections A 0.6-A 3.3 according to the coordinates of a stereotaxic atlas [7] were observed on response of 64 VPM thalamic neu- rons produced by stimulating different groups of trigeminal nerve and CN STT neurons.

The VPM neurons tested were divided into three groups depending on whether response occurred to stimulating different groups of trigeminal nerve fibers The "low-threshold" group consisted of 29 units responding to stimulation of low-threshold suborbital nerve affer- ents but not to reinforced stimulation of this nerve nor to tooth pulp stimulation. Two neu- rons responding to stimulation of high-threshold trigeminal nerve afferents only were classi- fied as "high-threshold" neurons and the remaining 33 responded to both high- and low-thresh- old stimulation of the orbital nerve as well as tooth pulp stimulation. These composed the "convergent" group of neurons. Stimulating the CGM with trains of stimuli led to the occur- rence of response in the form of several action potentials in 7 VPM thalamic neurons (4 cells from the "low-threshold" and 3 from the "convergent" groups). Latencies of these responses reached 30 msec. This response pattern only arose in the case of fairly intense stimulation (of the order of 200 ~A - Fig. 2). Applying a conditioned stimulus to CGM sites led to sup- pression of response induced by stimulating peripheral trigeminal nerve and CN STT afferents in a proportion of VPM thalamic neurons. Neuronal response was suppressed with a time inter- val of 50-250 msec between conditioned and test stimuli. Suppression of response in VPM thalamic neurons following CGM stimulation was noticed when a response occurred to CGM stimu- lation as well as when it did not (Fig. 2).

Conditionedstimulis applied to the CGM produced differing effects on the response of below threshold group of neurons induced by stimulating low-threshold suborbital nerve fibers. Response was suppressed in full in 7 units and persisted in a further 7, although numbers of action potentials declined (see Fig. 2a). A facilitatory effect was observed in one neuron. In this instance, recordings were made simultaneously from two cells, during which it was found that when activity in one of the two was suppressed by CGM stimulation, response was facilitated in the other (Fig. 3). A further ii neurons belonging to this group were acti- vated by CN STT stimulation. Applying a conditioned stimulus to the CGM suppressed both responses either partially or in full in 5 neurons (Fig. 4a and b), had no effect on the re- sponse of a further 5 units, and in just one cell suppressed response produced by CN STT stimulation, while that evoked by stimulating low-threshold suborbital nerve fibers was inhibited to some extent (Fig. 4c and d). Response was completely suppressed by applying a conditioned stimulus to the CGM in both neurons of the "high-threshold" group (see Fig. i])). This stimulus acted differently on the response of VPM thalamic neurons belonging to the "convergent" group, on the other hand.

510

SN (3.0)

-- ' i~7-

CGM+SN (3.0)

SN (3.0)

SN (3.0)

FI"~ C-GM + SN (3.0)

" II

SN (3.0)

CN S T T

�9 i

-- ; r,

CGM +CN SIT

CN SIT

' I ] b ~ I ~SmV f0msec

'CN SIT

CGM + CN SIT

, ,4..._~. -

CN SIT

~05 mV Fig. 4. Effects of applying conditioned stimulus to the midbrain central gray matter on response in two "low-threshold"neurons (a, b) induced by stimu- lating the suborbital nerve (SN) and the caudal nu- cleus of the spinal trigeminal tract (CN STT Re- maining notations as for Fig. 2.

In 17 neurons of this group, CGM stimulation led to depresslon of response produced by stimulating low-threshold suborbital nerve afferents and tooth pulp (Fig. ic and d) and re- sponse remained unchanged in 5 neurons; this stimulus suppressed only the response produced by tooth pulp stimulation in 7 units and facilitated both responses in one cell. Six neurons of the "convergent" group responded to CN STT stimulation. Applying a conditioned stimu].us to the CGM led to depression of the response to CN STT and trigeminal nerve peripheral affer- ent stimulation in 3 cells and to that induced by stimulating tooth pulp and CN STT in 2 of the neurons. Response induced by stimulating low-threshold suborbital nerve afferents were then inhibited only partially or not at all (see Fig. 5); response produced by tooth pulp stimulation but not by stimulating low-threshold CN STT and low-threshold suborbital nerve fibers did not change in this instance.

DISCUSSION

Our findings show that stimulating the CGM leads to activation of a limited number of thalamic VPM neurons only (10.8%). This stimulation exerts a mainly inhibitory effect. Applying a conditioned stimulus to the CGM suppressed activity both in neurons activated by CGM stimulation and those in which no activity had been observed. In the case of the former, no response to stimulating trigeminal nerve peripheral afferents arose; this could have been due to the protracted inhibition developing in thalamic neurons following excitation of what- ever origin [6].

Different mechanisms could underlie the inhibition observed in the response of thalamic VPM neurons not activated by CGM stimulation. Activity could be suppressed in these cells as a result of excitatory response produced in inhibitory neurons by CGM stimulation.

Since the 50-250 msec period of depressed thalamic VPM neuronal response matched that of depressed activity in oral nucleus neurons of the spinal trigeminal tract and the CN STT [3, 14] produced by applying conditioned stimulus to the CGM, it might be supposed that the reduced likelihood of responses appearing in thalamic neurons is due to inhibition of neuronal

511

SN (50) . PI CN STT _

_ ~ , . ~ - . - - - - - - - -

. . ~ ~ ~ - -

CGM+SN(3.0) CGM + PI CGfl + CN Sl~f

SN (3,0) Pz CN s r r

. ~ ~ ~.~ mV

20 msec

Fig. 5. Effects of applying conditioned stimulus to the midbrain central gray matter on response in a "convergent" neuron of the thalamic ventropostero- medial nucleus induced by stimulating tooth pulp, the suborbital nerve, and the caudal nucleus of the spinal trigeminal tract. Notations as for Figs. 2 and 4.

activity in the sensory trigeminal nuclei. However, the fact that response induced by stimu- lating peripheral afferents and the CN STT in the same thalamic VPM neurons indicates that the CGM has a direct influence on the activity of thalamic neurons. The main body of impulses traveling to the thalamic VPM proceed from the principal sensory nucleus and the effects of CGM stimulation on neurons of this formation have not yet been ascertained.

Our findings show that applying the conditioned stimulus to the CGM inhibits activity in neurons belonging to the "low-" and "high-threshold" and "convergent" groups of thalamic VPM neurons. Response induced in 41% of neurons by stimulating high-threshold afferents and in 51.5% of cells produced by stimulating low-threshold suborbital nerve fibers were sup- pressed. Comparing the effects of CGM stimulation on thalamic nonspecific medial nuclei and relay VPM, it may be seen that CGM influence in neurons of the former nuclei is more pro- nounced. It was thus seen that response produced by high-threshold afferent stimulations was suppressed in 100% of neurons as against 86% when stimulating low-threshold afferents of the trigeminal nerve,

Our findings would suggest that the CGM does influence the activity of thalamic relay VPM but less so than that of cells belonging to the nonspecific medial thalamic nuclei in cats.

Our data indicate that the CGM can successfully modulate the activity of thalamic relay VPM and under these circumstances CGM stimulation exerts a mainly inhibitory action. This effect is less marked than in neuronal activity of nonspecific medial thalamic nuclei, how- ever.

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