Physiology & Behavior, Vol. 16, pp. 727-733. Pergamon Press and Brain Research Publ., 1976. Printed in the U.S.A.

Sensory Afferents to the Caudate Nucleus

O. DIEZ-MARTINEZ, M. GARCIA MUI~OZ, G. PRIETO J. A. ROIG AND H. BRUST-CARMONA

Department o f Physiology, Facultad de Medicina, U. N. A. M., Mexico 20, D. F.

(Received 13 March 1975)

DIEZ-MARTINEZ, O., M. GARCIA MU~OZ, G. PRIETO, J. A. ROIG AND H. BRUST-CARMONA. Sensory afferents to the caudate nucleus. PHYSIOL. BEHAV. 16(6) 727-733, 1976. - In awake immobilized cats, stimulation of nonspecific thalamic nuclei (NCM, DM) elicits evoked potentials in the head of the caudate nucleus (CN). The evoked potentials (EP) in the ventral part of CN are opposite in sign to those recorded in the dorsal region of CN. The points of polarity reversal are grouped in the lower third of CN. Peripheral sensory stimuli (somatic and visual) evoked potentials with a 20 msec latency. These evoked potentials change their polarity in the same region as the thalamic evoked responses. Visual and somatic responding areas overlap widely. The advantage of bipolar recordings for better localization is discussed.

Caudate nucleus Sensory input Evoked potentials Bipolar recording

CHANGES of evoked potentials in different cerebral structures have been shown to be correlated with learning processes [13, 17, 18]. The caudate nucleus (CN) is one of these areas [ 8 ].

Moreover it is known that lesions of the caudate nucleus (CN) disrupt the performance of conditioned responses in experimental animals [20, 23, 26].

These observations stress the role played by the CN in complex functions of the nervous system, as processes related to maintenance of wakefulness, alerting, direction of at tention [24] as well as regulatory sensorimotor activities [4].

If the caudate nucleus does participate in learning processes one would expect to find a convergence of polysensory information through the diffuse projection thalamic system [ 1,11 ]. Neuronal connections between the intraiaminar thalamic nuclei and the head of CN have been described by many authors [5, 6, 16], and have been confirmed by electrophysiological studies [2, 15, 25]. The dorsomedial nuclei have also been shown to project to the caudate nucleus [ 14].

Our aim was to describe the topographic distribution of the sensory afferent input to this structure, in the hope this might clarify the mechanisms underlying the modifications of evoked potentials during conditioning which were observed by Grinberg et al. [9].

EXPERIMENT 1

METHOD

Animals and Surgery

Experiments were performed on 17 adult male and female cats weighing between 2.5 and 3.5 kg. Tracheos- tomy was performed under ether anesthesia. After artificial respiration was started, ether was no longer administered. The animals were kept immobilized with gallamine triodide, 20 mg IP. Local anesthetic, procaine solution (1%), was

injected in areas inervated by frontalis nerve, a division of the fifth cranial nerve, and by occipitalis major nerve (dorsal rami of the second spinal nerve). These 2 nerves supply the skin and the muscles of the dorsal aspect of the head. The area around the tracheostomy incision was also repeatedly infiltrated with procaine. Inervation of this region is supplied by the ventral rami of the third, fourth and fifth cervical nerves [22]. The animal was continuously kept warm with a thermal pad. Rectal temperature was measured in some animals. Despite immobilization the temperature never varied from 370C in these conditions.

The cat's head was kept fixed to a stereotaxic frame. The skull was exposed and electrodes were lowered through drilled holes into predetermined subcortical structures. The stereotaxic coordinates for the stimulation and recording sites were determined using the Jasper and Ajmone-Marsan Atlas [12]. Silver wire electrodes were used for recording. These consisted of 2 or 3 threaded wires, 0.5 mm in dia. insulated except at the tips. The recording surface consisted of the wire's cross section. Bipolar recordings were made using two such wires placed side by side or separated vertically by 1 or 2 millimeters. Monopolar recordings were made using a reference electrode placed in the frontal sinus. Stainless steel wires, 0.5 mm in dia. were placed in the thalamic nuclei for stimulation. (Centralis medialis n., Medialis dorsalis n).

Apparatus and Procedure

The evoked potentials were amplified with a Grass AC P-511 differential input preamplifier with a bandwidth of 0.1 Hz to 30 KHz. The preamplifier output was fed into a cathode ray oscilloscope (CRO) Tektronix, Type 565. In bipolar recordings, the preamplifier output was connected so that an upward deflection of the CRO sweep was produced when the deep electrode was negative relative to the more superficial one.

The potentials evoked by thalamic stimulation were observed on the CRO screen and photographed with a Grass

727

728 DIEZ=MARTINEZ E T AL.

Kymographic Camera, model C-4. Six sweeps of the CRO were superimposed in the same frame of the film. A Grass stimulator, Model S-48, with a SIU5 isolation unit, was employed to deliver single pulses to the thalamic nuclei. The pulses were 0.5 msec in duration, 7 to 10 V in amplitude, and applied at a rate of 1 per sec. Each stimulus triggered the CRO sweep.

The recording electrodes were lowered, step by step, to a desired depth into the caudate nucleus, homolateral to the site of stimulation (A = 16.0). The caudate responses to thalamic stimulation were recorded every half millimeter of a 10 mm descending track. To facilitate topographical localization of recording sites electrolytic lesions were made in specific areas or the lowerest point of the track from which recordings were obtained.

A lethal dose of pentobarbital was given to the animals at the end of the experiments. Their brains were perfused with 0.9% saline solution followed by 10% formaldehyde. The mounted histological sections with the electrodes tracks were used as negatives for photographic enlargement [lOl.

RESULTS

Monopolar Recordings

The evoked responses in the CN to thalamic stimulation

consisted of biphasic potentials. The onset of the response followed the stimulus artifact without apparent delay. The most prominent component was a positive wave with a peak latency of 29.9 msec as average and a total duration of 50 msec. Sometimes a small negative deflection was seen on the descending limb of the positive wave which had an average latency of 13.8 msec. The characteristics of this inflection were hard to determine due to its proximity to the stimulus artifact. Moreover the small negative wave was very variable in amplitude, and the location of the recording site seemed to influence amplitude relative to the positive wave.

Bipo lar R e cordings

The configuration of the EP as seen in bipolar recordings with electrode tips separated vertically by one mm does not differ considerably from that described in monopolar recordings except that the positive wave had a shorter average latency. The initial small negative wave was not normally seen in the bipolar recordings (Fig. 1). In several experiments in which the pair of bipolar electrodes was placed at the same level the evoked potentials were either small or absent. The largest EPs were obtained with electrode vertical separation of two millimeters. The form of the response was similar in all 3 types of bipolar recordings, differing only in amplitude.

% •

+4.5

+6.0

"t"3.0

+1.5 / /

m / /

m

/ /

FIG. 1. Caudate evoked responses to thalamic stimulation (NCM). Bipolar records from three different animals. Each column represents responses in one animal. The recording level in the caudate is indicated by numbers appearing to the left. A reversal of polarity of the responses, occurring predominantly in the ventral part (H3) is seen in all three animals. Six CRO sweeps were superimposed in each figure. In this figure and those following it, a downward deflection indicates positivity of the deepest electrode. Calibrations: Time =

20 msec; Amplitude = 100/~V.

CAUDATE SENSORY AFFERENTS 729

500

=L 300 v

su z o a. u~ ioo tu n..

I~ o Y o t& l I00

o w o

..i 3o0 I=

-2;0 " ~ ; 0 " *e'0 " ~ ' . 0

~x x ~ o j e ~

'---'',,, ,,,.--

~b s

p

I • s ~ ' o t

P O I N T OF R E C O R D I N G (DEPTH)

+ B I P O L A R ( L A T . ,X = 19.4 msec)

. . . . M O N O P O L A R ( L A T . ,X = 29.9 msec) 10 Ss

FIG. 2. Relationship between the amplitude of evoked responses to thalamic stimulation and the site of the electrode in the caudate nucleus. Abscissa: Amplitude of evoked responses (negativity upward). Ordinate: Horizontal level of recording (Jasper and Ajmone-Marsan, [12] ). The results from ten experiments have been averaged for each point. The continuous line represents bipolar recordings. The broken line corresponds to monopolar recordings. Larger amplitude responses are seen with monopolar

records, however, no reversal of polarity occurs.

Influence of Site of Recording on the EP

The EP changed in amplitude and in polarity as the recording electrode was lowered through the CN. The positive wave, seen clearly when the electrode was in the dorsal part of the CN, diminished in amplitude with further descent. The smallest responses were seen in the ventral part of this structure. At this level the polarity changed to negative. Figure 2 illustrates the change in amplitude and polarity of the EP as a function of the electrode position.

The EP obtained with monopolar electrodes also changed in amplitude as the electrode position varied but no changes in polarity were observed. The broken line (Fig. 2) illustrates the amplitude changes in relation with the position of the recording electrode.

EXPERIMENT 2

METHOD

In seven experiments, the responses in the caudate to peripheral stimulation were examined.

Using an experimental set up similar to that described above visual and somatic stimuli were given.

For somatic stimulation, square pulses (0.1 msec du- ration, 0 .01-1 V, frequency 1/2 sec) were delivered to the left radial nerve.

For visual stimulation, a flash (duration 10 usec, frequency 1/2 sec) from a PS 22 Grass Photostimulator was

used. The lamp was placed 30 cm away from the cat's head and was aimed at the eyes. Atropine sulfate solution was instilled in both conjunctival sacs, 4 hr before recording began. Dim lighting conditions were kept constant from that point on.

Both caudate nuclei were explored from A-12 to A-17 and from Lat-3 to Lat-6. The CN responses were compared with EP obtained simultaneously from thalamic nuclei VPL (ventropostero-lateral), GL (geniculate body) and NCM (centralis medialis).

RESULTS

Somatic stimulation evoked biphasic responses only in certain areas of the CN. In the dorsal part of the CN, the initial wave which had an average peak latency of 35 msec could be either positive or negative. In either case, it was followed by a wave of opposite polarity. The EP with a duration of 50 msec began to appear 20 msec after radial stimulation. In the ventral part of CN (H 3 to 0) a reversal in polarity of the first component was seen in 6 of the experiments (Fig. 3). Although the responses could be recorded in both CN, the highest probability of appearance was found contralaterally to the site of radial stimulation. Even though responses were picked up from A = 12 through A = 17 most of them were obtained in the frontal part of the caudate's head (Fig. 4 and 6). Monopolar recordings showed greater amplitude responses. However,

730 DIEZ-MARTINEZ E T AL

SOMATIC EVOKED RESPONSES (CAUDATE NUCLEUS)

BIPOLAR MONOPOLAR

3.5

2.5

1.0

0.5

- 0.5

FIG. 3. Caudate responses to somatic stimulation. (A = 17 [12] ). Monopolar and bipolar records (EP's) obtained at different horizontal levels within the caudate. These EP's were elicited by stimulation of the contralateral radial nerve. Right: Monopolar records, show large amplitude responses that maintain a similar waveform all the way down. Left: Bipolar records, change in form and polarity with descent. Calibrations: Time = 100 msec; Amplitude = 40 #V for left column; 200

#V for right column.

neither the conf igurat ion nor the polar i ty suffered not ice- able changes in a 10 mm descending track (Fig. 5).

With bipolar recordings however the EP appeared sud- denly, as the electrode was lowered, and changed in ampli tude and reversed its polar i ty in only 3 mm of descent. These modif ica t ions were generally related to the structures crossed by the electrode. No changes of la tency in the EP were detectable during the descent of the electrode. If the intensi ty o f the st imulus delivered to the radial nerve was decreased, the EP in CN also diminished in ampli tude. At a st imulus intensi ty just sufficient to elicit an EP in VPL no response could be de tec ted in CN. The EP's e l i c i t e d in VPL, NCM and CN upon radial nerve st imulation, had different latencies the shortest being that observed in VPL fol lowed by NCM responses, with the longest la tency seen in the CN.

Visual EP

Photic s t imulat ion evoked responses in CN less fre- quent ly than somatic stimuli. The la tency was variable, ranging f rom 50 to 70 msec. The waveform resembled the somatic evoked responses a l though a different t ime-course could be observed. No reversal o f polar i ty occurred while

the CN was being explored. Both somatic and visual EP's could be elicited or not at a single point of the CN (Fig. 5).

The left and right CN had the same responsiveness to visual stimuli. A similar number of evoked potent ia ls was found on ei ther side (Fig. 6).

DISCUSSION

Peripheral somatic and visual stimuli are able to produce EP's in bo th CN. These results conf i rm the previous data on histological connect ions be tween n. centralis medialis and the head of the CN [21] . In no case however have predictible regions o f caudate nucleus been ident i f ied as receiving an exclusive somat ic or visual input . Fu r the rmore a considerable overlapping occurs in the areas responding to bo th kinds of stimuli.

On the o ther hand, our recordings show a region in the ventral part of CN where responses reverse their polari ty. This zone would const i tute an electrical source and therefore a probable area for the input of thalamic afferents for bo th sensory modalit ies. The small ampli tude o f the potentials observed with bipolar electrodes in which bo th tips were at the same level, suggests a laminar dis t r ibut ion of these pathways in the CN. Al though the CN appears to

CAUDATE SENSORY AFFERENTS 731

THALAMUS ~ STIMULUS SiTE ~

SlTE FOR SOMATIC L ~'IMULATION

M.D. cl N.

N.C.M. C.N.

FIG. 4. Sites for thalamic stimulation (MD, NCM) are signaled by arrows in the left column. Electrode tracks where thalamic stimulation evokes responses in CN are shown in the middle column. Recording sites for both

somatic and visual stimulation in two different frontal plans appear to the right.

be histologically homogeneous, it is worth looking for a structural basis that explains these electrophysiological differences.

Responses to both types of stimuli could usually be elicited at the same point but in some cases there was no such coincidence. Exploring the same areas of the CN Albe-Fessard e t al. [2] were not able to find a somatotopic distribution of somatic afferents to this nucleus but, they showed that for these responses cortical relays were not necessary. On the other hand, the same authors [3] have shown that a single cell of the caudate can respond to several types of sensory stimuli (visual, acoustical and somatic). In a structure thought to play a significant role in integrative plastic processess, polysensory convergence is a requisite of utmost importance.

The topographical organization of the CN projections to dorsal thalamic nuclei has been shown by Frigyesi and Machek [7]. They showed that the development of synchronizing PSPs in n. ventralis lateralis was fastest during low frequency stimulation of the medial third of the

head of the CN. Thus, these projections might close a loop of intralaminar thalamic nuclei-head of the CN- dorsal thalamic nuclei-intralaminar nuclei which would control sensorial activity at the thalamic level and/or motor activity in different extrapiramidal projections. It might be that by means of this circuitry the CN modifies the sensory afferent transmission in the thalamic relays or the motor output as representations of the learning processes. The possible topographical organization has also been shown in be- havioral studies [ 19,27 ].

A fact worth noting was the inadequacy of monopolar recording for topographical localization of evoked re- sponses. Although monopolar records show large responses, these appear unchanged through the diverse structures explored when the electrode is gradually lowered. Bipolar records from the same areas show clear cut modifications related to the region of the caudate being investigated. Hence bipolar recordings must be employed when accurate mapping of responding areas is required in order to study the origin and significance of the EP in relation to learning.

732 D I E Z - M A R T I N E Z ET AL

CAUDATE NUCLEUS

SOMATIC EVOKED VISUAL EVOKED RESPONSES RESPONSES

4.5

1.5

, m m m e m ,

FIG. 5. Caudate responses to somatic or photic stimuli. Bipolar recording. Both types of responses may be obtained from a single point. (H 4.5 and 2.5). One millimeter below only

somatic stimuli elicited responses. Calibrations: Time = 50 msec; Ampli tude = 100 tzV.

CAUDATE 801qATIG EVOKED

RESPONSES

~k~. No Ft. Ilr.O

NUCLEUS VmUAL EVOKED

R E ~ a F . 8

~ . SO Ft. I?.O

. . i~ " '̧:~

. . ° . . . g ° * * , . . . . o . ° m ~ * ~ * ° f * 1

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FIG. 6. Caudate distr ibution o f evoked response to somatic or visual stimuli. The responding areas to bo th kinds o f stimuli overlap widely. Larger responses to somatic stimuli were seen in

Plane 17.

C A U D A T E S E N S O R Y A F F E R E N T S 733

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