Modification of single cell responses in the posterior hypothalamus to sensory stimuli by caudate and globus pallidus stimulation and lesions

402

BRAIN RESEARCH

M O D I F I C A T I O N OF S I N G L E CELL RESPONSES 1N T H E P O S T E R I O R H Y P O T H A L A M U S TO SENSORY S T I M U L I BY C A U D A T E A N D GLOBUS P A L L I D U S S T I M U L A T I O N A N D LESIONS

S H A U L F E L D M A N AND N A C H U M D A F N Y

Department of Nervous Diseases, Laboratory of Neurophysiology, Hadassah University Hospital and Hebrew University-Hadassah Medical School, Jerusalem (Israel) (Accepted March 20th, 1968)

INTRODUCTION

Previous studies on single cells in the anterior hypothalamus in cats have demonstrated that their spontaneous activity and responsiveness to sensory stimuli are modified by caudate nucleus stimulation and lesions 5. To further elucidate the role of caudate nucleus in the regulation of hypothalamic electrical activity, its effects on posterior hypothalamic units were investigated with the purpose of comparing the influences on these two hypothalamic regions. Furthermore, as the caudatalhypothalamic relations may be mediated by the globus pallidusl0, '~ the role of this structure on the afferent input into the hypothalamus and its possible participation in caudate inhibition were investigated as well. Subsequently the present study describes the effects of various striatal stimulation and lesions on the responsiveness of posterior hypothalamic units to sensory stimulation. MATERIALS AND METHODS

Experiments were performed on 40 cats, in which a total of 608 units were evaluated, The various operative procedures, including venesection, sciatic nerve exposure and the introduction of electrodes were performed under pentobarbital anesthesia. The pupils were dilated by atropine sulfate. The brain was covered with agar to diminish pulsation. In 12 animals either unilateral or bilateral electrolytic lesions were placed in the head of the caudate nucleus or bilateral lesions in the globus pallidus, by passing a DC current of 5 mA for 20 sec. Only those animals which recovered completely from the operation were used 5-10 days after surgery in the acute electrophysiological experiments. In addition, bilateral lesions, which produced a state of coma, were placed in the midbrain reticular formation in 5 other animals which were studied 2 days later. In three other experiments the cerveau isol~ preparation was used. Extracellular unit activity was recorded under light pentobarbital anesthesia in the posterior hypothalamic nucleus at stereotaxic coordinates Brain Research, 10 (1968) 402-417

403

ST RIATAL EFFECTS ON HYPOTHALAMIC UNITS

F 8 . 5 : L 0 . 5 and H - - 2 to H - - 3 (ref. 15) with stainless steel microelectrodes (tip 1-3 #), which were prepared as described previously 5. The units were photographed by a Grass camera run continuously, from a Tektronix 502 oscilloscope. A Grass P5 preamplifier, which was connected to a cathode follower, was used for amplification. Single photic, acoustic or sciatic (3.5 V, 0.1 msec) stimuli were applied every 2 sec and their effects on the unit firing were observed for 2000 msec after each stimulus in relation to the spontaneous activity. This spontaneous activity was recorded both before and for control purposes between the application of the different sensory stimuli. The effects of a single conditioning caudatal or pallidal stimulus (3.5 V, 0.1 msec), on a subsequent sensory response were investigated at different time intervals, as well as the effect of lesions on the responsiveness of the hypothalamic units to sensory stimuli and on the interaction of central and peripheral modalities. Only those units in which all the three sensory modalities were tested on the spontaneous TABLE 1 EFFECT OF

STRIATAL

S T I M U L A T I O N OR

LESIONS ON

SENSORY RESPONSIVENESS OF

POSTERIOR H Y P O -

TIIALAMIC UNITS

Table IA d e m o n s t r a t e s the effects of the three sensory modalities o n the s p o n t a n e o u s activity a n d the interaction of conditioning striatal with sensory stimuli at 25 nqsec interval. Table IB d e m o n strates the responsiveness o f the units to the three sensory modalities in a n i m a l s with chronic striatal lesions a n d IC the effects of e x t r a h y p o t h a l a m i c lesions on the interaction between caudate and sensory stimuli. T h e n u m b e r s in parentheses indicate the n u m b e r of units used in each experimental group. T h e nLimbers underlined, under the three sensory modalities, d e m o n s t r a t e the total percentage of units which showed a significant change in the rate of firing a n d these are subdivided into those in which there was an increase ( t ) or decrease ) in the rate of firing.

Photic Acoustic (+) 1 C-) (+) I (-) 60.6"/,, 697 %

Modality SENSORY MODALITIES CONTROL

IPSILATERAL

CAUDATE

(175}

61.o 1.7

A CONTRALATERAL CAUDATE STIM.(SO)

GLOBUS

PALLIDUS

BILATERAL

STIN.

CAUDATE

IRSILATERAL

(75)

(l.@)

LESION

(51)

B CONTRALATERAL

BILATERAL

CAUOATE

,PSILATERAL

IPSILATERAL

LMRF

LESION (50)

GLOBUS PALLIOUS LESIONS ( 5 0 )

CAUDATE

r~ p L;_~;o,~

CAUDATE

STIM

IPSILATERAL

EC~ye~u is~Id

98.3

]

7. 7

92.0

I0,5

J 25.7 63.9 % 79.3 I 20.7

12.5

gO.O

/.2.0 % ]

(50)

58.0

[

19.1

J

89.5

42.0

!

89.7

I

13.0

87,5 7.1 36,5

I

68.0

9& 4

[

87,0

56.0 %

I I

37. 6

/.6.0 %

69.3 % 58.0

I

92.9

73.1% I 23.0

770

68.6 %

32.0 82.5

I

17.5

68.0 %

%

] 41. 7 59.5 ] gO.5 44.0 % /-.6.0 % 86. ,~ ] 12.6 73.1 ] 26.9 58.3

500 % 53.0 38.0 [

/./..6 % 10.3.._

3.6

66.6 % 63.4

60.0% 80.9

92.3

/.8.0 %

66.7 %

I

]

I

73.3%

38.0 %

74.3

60.0

43.3 62.4

38.0 %

(65) CAUDATE

8.0

STIM.

Les~

[

J

69.3%

500%

56.0 % zo I 93.o

LESIONS

CAUDATE

39. o 56.7

i

80.0 %

STIM. (125)

Sciatic (+) I (-) 66.0 %

/.6.0 30.0

I

%47.0 I 48.0 i 52.0 % 29.2 % 7oo

10.5

] 89.5

/.7.2 %

STIM.

(~I

11.8

I

88.2 Brain Research, 10 (1968) 402-417

404

S. FELDMAN A N D N. DAFNY

activity and in which the interaction between central and peripheral stimuli were investigated, were included in this study. The total number of spikes was counted from all the films and the responses after every stimulus were evaluated from at least 10 sweeps of 2000 msec duration each, for all the modalities in each of the units. The data were evaluated as to changes in the rate of firing resulting from the stimulus, using the critical ration ( C R ) t e s t ( C R - ( E - S)/~/(E ÷ S) when E a n d S signify evoked and spontaneous activity, respectively). The change in the pattern of firing was determined by counting 10 periods of 200 msec each, comprising one sweep of 2000 msec, following the central or peripheral stimulation and the chi-square (X 2) test calculated at various levels of significance. A unit showing either a change in the rate or pattern of firing was defined as a responsive unit. The position of electrodes and lesions were determined histologically at the end of the experiments. RESULTS

Effects o f striatal stimulation on sensory responses

As demonstrated in Table IA and confirming our previous observations 4 on the sensory responses of single cells in the posterior hypothalamic nucleus. 60-70~o of the 175 units studied, responded significantly by a change in the rate of firing to each of the three sensory modalities. Most of them showed an increase in the firing rate following sensory stimulation. In order to determine the most effective time interval at which a conditioning striatal stimulus will inhibit a subsequent sensory response. intervals of 25, 50, 100 and 200 msec were studied in 100 single cells. From Fig. 1. which is a compound histogram of 75 cells, it is evident that at the interval of 25 msec between a conditioning caudate and test sensory stimulus the strongest inhibition of the sensory response of all the three modalities was obtained. The inhibitory effect manifested itself both in the reduction of the overall rate of firing, as well as in the change in the pattern of firing. While the average firing rate following the three sensory stimuli was 11.1, 11.5 and 12.7 per 2 sec. at an interval of 25 msec the conditioning ipsilateral caudate stimulus caused a reduction to values of 5.6, 5.5 and 6.6. respectively. At a 200 msec interval between the i psilateral caudate conditioning and the test sensory stimulus, the rates of firing were essentially identical to the controls. While the control record showed a pattern of three peaks (200-400 msec: 1000-1200 msec; 1400-1600 msec), during the period of 2000 msec after the sensory stimulus, the interaction at an interval of 25 msec between the ipsilateral caudate and the sensory stimulus produced essentially an 'ascending' histogram, with one peak which was at 1400-1600, 1200-1400 and 1800-2000 msec following photic, acoustic and sciatic stimuli, respectively. At a 50 msec time interval there was no essential difference in the histogram from the 25 msec interval following photic and sciatic stimulation, however following acoustic stimulation the maximum peak was at 1400-1600 msec. At a time interval of 100 msec the three peaks became evident'as in the controls. in spite of the overall reduction in the rate of firing and complete recovery was obtained at an interval of 200 msec. In contrast to these findings, conditioning ipsilateral globus pallidus stimuli at 25. 50, 100 and 200 msec. preceding the sensory stimulus. Brain Research, 10 (1968) 402-417

405

STRIATAL EFFECTS ON HYPOTHALAMIC UNITS

20i_Flash Cd -Flash msec 100 msec 200

u

20' Click

~ :[~ tn 1

Cd

Click

--

msec msec m 2i~ 5 ~ 1 - ~

200

Click

Gtobus Paltidus Flash 25 50 100 msec msec msec

200 m sec

Gtobus PaUidus Click

ec

50 100 200 msec msec msec msec

_~

_

Cd - Sciatic

Sciatic

100 ~

Flash

20

25

50

msec

msec

Sciatic

GLobus Pallidus Sciatic 50 100 200 msec msec msec msec

°§o

oo

o

o

oaE

oooo ~o

~o o o

Fig. 1. Compound histograms during a period of 2000 msec after stimulation showing the effects of the three sensory modalities on the spontaneous activity of 75 units in the posterior hypothalamus (white bars) and the effects of the interaction between conditioning ipsilateral caudate nucleus and the three sensory modalities at 25, 50, 100 and 200 msec intervals (black bars). Similar data are shown in the figure for another group of 25 units in the posterior hypothalamus and the effect of the ipsilateral globus pallidus on the sensory input. The horizontal line in the histogram demonstrates the average firing rates of the cells following stimulation.

have reduced very considerably the overall firing rate. While the rates of firing following the three sensory modalities in this group of cells were 11.0, 11.4 and l 1.9 spikes per 2 sec, the considerable reduction in the unit discharge persisted essentially unchanged (3.4-5.1 per 2 sec) throughout the whole 2000 msec poststimulation period up to an interval of 200 msec. Also, the original triple peak response of the histogram was abolished, and only at an interval of 200 msec there was a tendency towards the return to the control histogram (Fig. 1). As the 25 msec interval was found to be the most effective in inhibiting the sensory activity in the posterior hypothalamus, the effects of a conditioning caudate stimulus on sensory responses were studied at this time interval in more detail in a group of 225 cells. As evident from Table IA about 70-80% of the cells out of 125 units, responded significantly to an ipsilateral caudate nucleus stimulation by a change in the rate of firing, the greatest majority of these cells, more than 90~;, showing inhibition. This change in responsiveness was particularly evident after Brain Research, 10 (1968) 402 417

406

S. F E L D M A N

AND N.

DAFNY

p h o t i c stimulation. F o l l o w i n g c o n t r a l a t e r a l c a u d a t e (50 units) or globus pallidus (75 units) stimulation, the ratio between cells which were facilitated o r inhibited by the central stimulus r e m a i n e d essentially the same. however the total n u m b e r o r responsive units was c o n s i d e r a b l y reduced, when c o m p a r e d to the responsiveness following ipsilateral c a u d a t e stimulation. The analysis o f the p a t t e r n o f responsiveness, as defined previously has shown that m o r e t h a n 40 % o f the cells r e s p o n d e d significantly to the three sensory m o d a l i t i e s by a change o f pattern, the greater m a j o r i t y showing a highly significant change ( P < 0.001) (Table II). F o l l o w i n g the i n t e r a c t i o n o f a c o n d i t i o n i n g ipsilateral c a u d a t e stimulus with a test sensory response at an interval o f 25 msec. there was an increase in the percentage o f the t o t a l responsive units by 24, 12 a n d 21.4 % for the three sensory modalities, respectively. The subdivision o f the responsive cells, at the various levels o f significance, has d e m o n s t r a t e d a m o r e or less even d i s t r i b u t i o n for the various units showing interaction between ipsilateral c a u d a t e a n d p h o t i c stimuli. F o r the i n t e r a c t i o n with acoustic stimuli, half o f the cells r e s p o n d e d at a low significance. O n the o t h e r hand. the majority o f units showing an interaction between ipsilateral c a u d a t e a n d sciatic stimuli, have r e s p o n d e d at a highly significant level. As evident f r o m Table II. the percentage o f responsive units to change o f pattern, following the TABLE II DISTRIBUTION OF RESPONSIVE UNITS TO CHANGE OF PATTERN AT VARIOUS LEVELS OF SIGNIFICANCE

This table demonstrates in a group of 175 cells the total percentage of responsive units to change of pattern and their distribution at various levels of significance, following the stimulation of the three sensory modalities. It also shows the total percentage of responsive units and their subdivision at various levels of significance, following the interaction between a conditioning striatal and a test sensory stimulus at an interval of 25 msec. TOTAL "/o OF RESPONSIVE UNITS

SENSORY MODALITY

p<0.01

p<0.001

p<0.05 i

PHOTIC

41.3 %

61.2 %

19.4 %

19.4 %

ACOUSTIC

41.3 %

54,8 %

12,9 %

32.2 %

SCIATIC

/.6.6 %

74.3 %

17.1 %

Ipst[ateral

Cd

I

3/,,8 % j

Striata[-25 msec Con~ra[atera[ Cd Phot;c Globus Pallidus

8.6 % a

[]

]

I

38.7 % I

14.0 "/.

25.5 % '

1~,3.,.

28.6 %

]

f

tsT1 .Jo I

Striata[ 25 msec Acoustic

Ipsilatera[ Contra[atera[

Contralateral G[obus

Cd

I,oo.I

20.0 %

Cd

I I 0.0%

20.0 % 70,5% [

68.0 o/. I Cd

Pat[[dus

Brain Research, 10 (1968) 402-417

15.0 %

35.0% [

6[ob~Js "Patlld.u s Ipsiiatera(

Striatal 25 msec Sciatic

53.3%

Cd

F-o-L I 20,0"/,

!27.~.,i~;io';

50.0 "/o i

1,oo. E

~

.:oao

L30.0 ./,

I70.0 ' I tl.8 %

17.6 % 1

30.0 %

i~0 0 ".

STRIATAL EFFECTS ON HYPOTHALAMICUNITS

407

interaction of the contralateral caudate and particularly of the globus pallidus with the three sensory modalities, decreased considerably and those which were responsive showed a low degree of significance. This corresponds to the lack of particular pattern, as demonstrated in the histogram showing the interaction between the globus pallidus and the sensory stimuli (Fig. 1). Fig. 2 is a superimposed compound histogram comparing the effects of interaction between the three sensory modalities with the contralateral and ipsilateral caudate nucleus and the globus pallidus, respectively. It is evident from this figure that while the three striatal structures inhibit the overall rate of firing, the ipsilateral caudate is more effective than the contralateral caudate, particularly in the first 1000 msec after the stimulation, while the pallidal inhibition is sustained throughout the whole 2000 msec poststimulation period. The units were also analyzed as to the period of total cessation in firing following the interaction, at an interval of 25 msee, between the central and peripheral stimulus. In contrast to the majority of units which showed a reduction in the rate of firing throughout the whole poststimulatory period, it is evident from Fig. 3 that 9, 1 and 11 cells showed a complete arrest of firing during the whole 2000 msec period after the interaction between the ipsilateral caudate nucleus and photic, acoustic and 20

15

10

~

5

I''2° '

LU 0

I

'''

''2°°°

i

0

i

i

i

i

1000

I

,

I

2000

o

,,=, 15

I

z~ lO

5I0i-- I 0

GLOBUS PALLIDUS (75)

'i ' I 1000

I SENSORY STIMULI (175) CONTRALATERAL CAUDATE (50) IPSILATERAL CAUDATE (125)

' 2000 msec

Fig. 2. Compound superimposed histograms during a period of 2000 msec after stimulation showing the effects of the three sensory modalities on the spontaneous activity of units in the posterior hypothalamus and comparing the effects of different conditioning striatal stimuli preceding the sensory stimulus by 25 msec. Brain Research, 10 (1968) 402 417

408

S. FELDMAN AND N. I)AFNY

Ipsitateral

Contralateral

Cd

Globus

Cd

PaLLid us

-Flash

o....

o

-

FLash

o......

o

-

Flash

o......

-Click

,

,

-

Click

,

•

-

Click

,---~,

-

• ......... A

-

Sciatic

• ......... •

-

Sciatic

A. . . . . . . . . . •

Sciatic

o

F 10 I-

! ,i

"f / i

i/\/

P" 0 , |

0

I

"A ,

"

il

, '\A;I ,

i

i

1000

t J

•

:

\1/ , "0- ~l--t-

2000

0

1000

2000

0

1000

2000

msec

Fig. 3. Graphs, the points of which demonstrate the number of units in the posterior hypothatamus in which there was a total arrest of firing at various periods following the interaction between a conditioning striatal and a sensory stimulus, at an interval of 25 msec. sciatic (Fig. 4) stimuli, respectively. 21,27 and 21 cells showed a total inhibition during a period of 200-1800 msec after stimulation (Fig. 5). As a result of the interaction between a conditioning contralateral caudate and the sensory stimulus, not a single cell has shown complete arrest in firing during the whole 2000 msec period. The interaction caused total inhibition in the firing of 18, 14 and 15 cells following the stimulation of the three sensory modalities, respectively, the majority showing inhibition only at the first period of 200 msec. Thus this is another indication of the greater effectiveness of the ipsilateral caudate. Finally, the interaction at a 25 msec interval between the ipsilateral globus pallidus and the three sensory modalities caused total inhibition during the 2000 msec after sciatic nerve stimulation in three units only. 14, 9 and 14 units showed partial inhibition when the globus pallidus was interacted with the three sensory modalities, respectively. In order to confirm the impression gained from different groups of units in the hypothalamus, that the inhibitory effect of the ipsilateral caudate nucleus was more effective than that of the contralateral, both modalities were applied to the same group of 15 cells. The results of the interaction between the nuclei and the three sensory modalities respectively, at an interval of 25 msec, in relation to the effects of the sensory stimuli on the spontaneous activity were studied. As expected. ~the statistical analysis has shown that while the sensory response to the three modalities was inhibited in 13. 11 and 12 cells by the stimulation of the ipsilateral caudate nucleus. only 8, 6 and 8 units were similarly affected by the contralateral caudate nucleus. 6, 6 and 7 units responded to both caudate nuclei as well as to photic, acoustic and sciatic stimuli, respectively. Similarly, the effects of the ipsilateral caudate nucleus and the globus pallidus were tested in another group of 20 cells in the posterior Brain Research, 10 (1968) 402-417

4-()~)

STRIATAL EFFEC'FS ON t~YPOTHALAMI(' UNIIS

V psitaterat

Sciatic

Spon

Cd -Sciatic

]audate

J5~O/JV z°O msec

30125 ¢'4

20

.& tn

!!!i~

15

"s o z

10

!ii!iiI ili!iii

ii

lOOO

2000

msec

"~

..... !!iiiil t000 msec

Ii:i:ii

i;!1

i;ii~! !i!!ii!

2000 0

1000 msec

2000 0

I000

2000

msec

Fig. 4. Single cell recordings in the posterior hypothalamus and their respective histograms of spontaneous activity, the effects of sciatic and ipsilateral caudate stimulation on the spontaneous activity as well as their interaction at an interval of 25 msec. The units in this and subsequent figures were redrawn from the original films.

hypothalamus. In accordance with the results obtained in the previous groups, the interaction between the caudate nucleus and the three sensory modalities caused inhibition in 16, 13 and 17 cells, while the interaction with the globus pallidus produced inhibition in only 11, 9 and 12 cells, respectively. Also, in this group 6, 6 and 7 cells responded to both the caudate and globus pallidus as well as to the three sensory modalities. Consequently, 10, 7 and 10 cells interacted with the caudate nucleus only and 5, 3 and 5 cells with globus pallidus only in relation to the three sensory modalities. In those units which responded to both the caudate and globus pallidus, the latter had a stronger inhibitory effect both on the spontaneous and evoked activity (Fig. 6).

Effects of striatal lesions The effects of bilateral, ipsilateral or contralateral caudate nucleus lesions as well as bilateral globus pallidus lesions on the responsiveness to sensory stimuli, were studied. As evident from Table IB there was no change in the overall percentage of responsive units (CR test) in the caudate lesioned animals, when compared to Brain Research, 10 (1968) 402-417

410

S. FELDMAN AND N. DAFNY

Spon.

lpsilateral Caudate

Flash

Cd.-

Flash

!lLii

20

m

!/!

15

m

, j soo.,,v 200 m s e c

I

I

10

1000

2000 0

msec

I .

1000 msec

.

.

2000 0

.

1000

2000 0

1000

msec

2000

msec

Fig. 5. Single cell recordings in the posterior hypothalamus and their respective histograms of spontaneous activity, the effects of photic and ipsilateral caudate stimulation on the spontaneous activity, as well as their interaction at an interval of 25 msec.

Spon

Click

Cd.

53

GP 12

21

Cd 25msecclick 34

GP 25msec click 22

15

tota[ spikes

~, 5oopv 200msec

~o

5

0

1000

2000 0

1000

2000 0

1000

2000 0

1000

2000 0

1000

2000 0

1000

2000reset

Fig. 6, Single cell recordings in the posterior hypothalamus and their respective histograms of spontaneous activity, the effects of acoustic, ipsilateral caudate and globus pallidus stimulation on the spontaneous activity, as well as the interaction at a time interval of 25 msec between conditioning caudate or pallidal and acoustic stimuli.

Brain Research, 10 (1968) 402-417

STRIATAL EFFECTS ON HYPOTHAI.AMI( LNIIS

41 t

intact animals, following the three sensory stimulations. However, more cells were facilitated by the three sensory modalities ..... out of the total number of responsive units - - in cats with ipsilateral or bilateral caudate lesions. Thus, while the difference between facilitatory and inhibitory cells in intact animals was 22.0 and 24.8"ii following photic and sciatic stimulation respectively, the corresponding difference after the ipsilateral caudate lesion, was 56.8 and 65.01~,. The relation between the facilitatory and inhibitory cells in the contralateral caudate lesioned animals was essentially the same as in intact cats. The total percentage of responsive cells to sensory stimuli following the globus pallidus lesions was reduced by 18.6, 25.7 and 20.0~, for the three sensory modalities, in relation to controls. However, there were much more facilitatory units in such animals. While the difference between facilitatory and inhibitory cells following acoustic stimulation was 13.4',!-, in intact animals, this became 72.8 ~, in the globus pallidus lesioned cats. The examination of the overall rate and the pattern of firing following sensory stimuli during the period of 2000 msec after stimulation in the bilateral and ipsilateral caudate and globus pallidus lesioned animals, has shown a definite difference in relation to the intact cats (Fig. 7). Such lesions caused no change however in the spontaneous firing of the hypothalamic units. Following the sensory stimuli in the abovementioned lesioned animals, there was a considerable increase in the overall rate of firing which was particularly evident in the globus pallidus lesioned cats. As described previously, the control pattern of the histogram following stimulation of the three sensory modalities consisted of three peaks 4. The effective lesions reduced their number and changed their position within the histogram. Following photic and sciatic stimulation in the caudate lesioned animals there appeared two peaks. The first one already at 200 msec (in contrast to 40~ msec in controls), while after acoustic stimulation only the late peak persisted. The early peak following the sciatic response was very prominent. Contralateral caudate lesions produced no change in the firing rate or pattern following sensory stimuli, in relation to controls. The interaction of the ipsilateral caudate nucleus with sensory stimuli at a 25 msec interval in animals with bilateral globus pallidus lesions showed in 50 cells a considerable reduction in the responsiveness as compared with intact cats (Table IC). Thus 80.0 % of the units responded in intact cats to caudate-photic interaction, while the same stimulation affected only 38.0'~,~i in cats with globus pallidus lesions. Subsequently, many units did not respond to caudate sensory interaction (Fig. 8). Furthermore, the percentage of facilitatory units in the lesioned animals was also considerably increased. Thus 1.7'/',,~ were found in non-lesioned animals following caudate-photic interaction, as compared to 58.0 ~ in the lesioned animals. Essentially, similar results were obtained for the two other modalities in the globus pallidus lesioned cats. The effects of bilateral caudate lesions on the interaction between conditioning ipsilateral globus pallidus and sensory stimuli were studied in 23 cells. When the results were compared with the interaction of globus pallidus with sensory stimuli in intact cats, essentially the same results were obtained as to the total responsiveness of the cells as well as to the distribution between facilitatory and inhibitory units. Brain Research, 10 (1968) 402-417

412

S. FELDMAN AND N. DAFNY

....... CONTROL (175 u n i t s ) • • B I L A T E R A L Cd L E S I O N S (/-8 . . . . . ~ I P S I L A T E R A L Cd L E S I O N (51 • • CONTRALATERAL Cd LESION ............... GLOBUS PALLIDUS LESIONS

Units) units) (50units) (50 u n i t s )

U

mSpontaneous

FLas h

S c i a tic

Crick

UI

•F, 30

~

•

20

.I0

E

c

--o

10

--

•

,~'A

'L

",m

L

,,,I <

.... 1000

I

2000

I ....

0

1,,,,) 1000

( .... 2000

0

I .... 1000

1

2000

I ....

0

I .....

1000

L

2000

msec

Fig. 7. Average curves showing the s p o n t a n e o u s activity of single cells in the posterior h y p o t h a l a m u s during a period of 2000 msec in intact cats (control) as well as in animals with various striatal lesions. The figure also d e m o n s t r a t e s the effects o f photic, acoustic and sciatic stimulation on the pattern o f firing of units in intact a n i m a l s a n d those with chronic caudatal or pallidal lesions.

To elucidate the possible role of the brain stem in the inhibitory effects of the caudate on units in the posterior hypothalamus, the interactions of conditioning ipsilateral caudate and sensory stimuli, at an interval of 25 msec, were studied both in animals with midbrain reticular formation lesions and in cerveau isol6 preparations. As indicated in Table IC the percentage of responsive units to change of firing was reduced in relation to intact animals, however there was no appreciable change in the ratio between units which were facilitated and inhibited by sensory stimuli, in comparison to intact animals. DISCUSSION

The present experiments extend previous observations on the sensory projections to the hypothalamus and their modification by various extrahypothalamic structures 7 11. The corpus striatum has been found to be very effective in modifying hypothalamic projections and responsiveness to sensory stimuli. The ipsilateral caudate nucleus, and to a lesser extent the contralateral caudate, had a strong inhibitory effect on the posterior hypothalamus. This is evident from the fact that almost each unit showed a statistical reduction in the firing, following caudate-sensory interaction, and subsequently the overall rate of firing was significantly reduced. While the caudate Brain Research, 10 (1968) 402-417

STRIATAL EFFECTS ON HYPOTHALAMI(' UNITS

413

i

Total spikes

Click 178

Sport 106

Cd 111

Cd, 25rnsec click 1B6

d

2oo~v

9AI3 ~

28 24

20 '~" 16

m 0

1000

2000 0

1000

2000 0

1000

2000 0

1000

2000msec

Fig. 8. Single cell recordings in the posterior hypothalamus, and their respective histograms, oF spontaneous activity, effects of acoustic and caudate stimulation on spontaneous activity as well as

the interaction at a time interval of 25 msec, between a conditioning caudate and acoustic stimulus in an animal with bilateral chronic globus pallidus lesions. inhibitory effects were most prominent in the first 1000 msec after the interaction between the caudate and the sensory stimulus, the pallidal inhibition remained sustained throughout the whole 2000 msec period. Similar effects were obtained on the spontaneous activity of single cells in the posterior hypothalamus, and this phenomenon may indicate the participation of different neural pathways. Recent studies la have analysed the caudate inhibition in relation to somatosensory responses of neurons in the medial diencephalon. Relevant to the present experiments are the findings that the caudate nucleus inhibited most neurones of centrum medianum and lateral dorsomedian nucleus of the thalamus, but relatively few cells in the subthatamus. Only 20 ~o of peripherally responsive units in this area, which is situated more laterally to the zone explored in the present experiments, were inhibited by caudate stimulation. In the region explored in the present study a much higher percentage of units was inhibited by caudatal stimulation in spite of the fact that both the subthalamus and the posteromedian hypothalamus have a high degree of convergence of sensory impulses 4,~1,12. The percentage of units inhibited by the caudate in the two explored areas in the thalamus was found to be as high as in the present study in the hypothalamus. The duration of the inhibition was found to be greater in the centrum medianum than in the dorsomedian nucleus, but still much shorter than in the hypothalamus. The ineffectual inhibition of the late discharge in the thalamus thus contrasts with the prolonged inhibitory effects exerted by the striatum on the hypothalamic neurones and may reflect different neural mechanisms involved. Brain Research, 10 (1968) 402-417

414

S. F E L D M A N A N D N. D A F N Y

Chronic ipsilateral or bilateral caudate lesions have not changed the total number of responsive units to sensory stimuli, in contrast to their effects on the anterior hypothalamic units, where the percentage of responsive cells was reduced ~. However, they have changed the ratio within the group of responsive units in favor of those cells which were facilitated by the sensory stimuli. Consequent to this change in responsiveness there was an increase in the overall firing rate after sensory stimulation, both due to an increase in the percentage of facilitatory cells as well as an increase in the firing rate of the individual units. Though the destruction of the globus pallidus caused a slight reduction in the number of responsive units, it has produced a great facilitation in the overall firing rate - - even more than that caused by caudate lesions - - due to the fact that most cells have responded by a very considerable increase in the firing rate after sensory stimulation. These results are thus consistent with its strong and sustained inhibitory effect when intereacted with the sensory stimuli in intact animals. Our previous and present studies of stimulation and lesion experiments delineate some of the pathways involved in the inhibitory effects of the corpus striatum on the hypothalamus. Though no direct anatomical connections have been demonstrated between the caudate nucleus and the hypothalamus 21,22 our previous experiments have demonstrated short latency (3-4 msec) potentials upon stimulation of the ipsilateral head of the caudate nucleus and the recording in the posterior hypothalamus. These evoked potentials were able to follow high frequency stimulation and were resistant to pentobarbital anesthesia and anoxia, suggesting the presence of oligosynaptic projections 1°. The finding of similar short latency pathways between the medial globus pallidus and the hypothalamus are in agreement with the existence of anatomical connections between these two structures 1~. In view of the existing connections between the caudate and globus pallidus 22 it is possible to envisage a caudatal -pallidal-hypothalamic inhibitory pathway. Studies by Krauthamer and Albe Fessard is have demonstrated that inhibitory effects on cortical evoked potentials were exerted by stimulation of the dorsal and ventral regions of the head of the caudate nucleus as well as the globus pallidus. Further experiments by Benita and Krauthamer "~, using the localized refrigeration technique, have suggested that the inhibitory influx is propagated from the dorsal to the ventral region and it may be therefore of interest that the most prominent hypothalamic evoked potentials were recorded in our experiments 1° upon stimulation of the basal region of the head of the caudate. Further support for the existence of the caudatal-pallidal-hypothalamic pathways is suggested by the finding that chronic lesions of the globus pallidus have reduced considerably the percentage of hypothalamic units, which were inhibited by caudate stimulation. Similarly, refrigeration of the globus pallidus has blocked the inhibitory effects of the caudate on the cortical evoked potentialsL The fact that the pallidal lesions only reduced but did not abolish the inhibitory interaction of the caudate with sensory stimuli in the posterior hypothalamus and that a considerable number of cells were still inhibited by caudate stimulation would indicate that there exist extrapallidal pathways which mediate these inhibitory effects. In spite of the total reduction in the number of responsive units to caudate Brain Research, 10 (1968) 402-417

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stimulation in such preparations, a larger percentage of cells were facilitated by the interaction between caudate and peripheral stimuli when compared to controls. This would indicate that the presence of the globus pallidus has exerted a strong inhibitory effect on the responsiveness of hypothalamic units to sensory stimuli and its removal has revealed facilitatory phenomena, which have been described in the cortex6,14 and subcortical structures ~ upon caudatal stimulation. Thus, the caudatal effects on the hypothalamus in intact animals, observed particularly in the strong early inhibition, may be envisaged as a result of a summation of impulses arriving both through the globus pallidus as well as other pathways. Furthermore, there is some evidence that the caudate and globus pallidus affect to a certain extent different populations of hypothalamic neurones as these two structures inhibit respectively the activity of units which react differently to peripheral sensory stimuli. Also, the present experiments have shown that there exist hypothalamic sensory units which are not affected by striatal stimulation, others which are influenced both by the caudate and globus pallidus and still other cells which are inhibited only by the caudate or globus pallidus, respectively. These facts may support the assumption for the existence of both convergent and separate pathways from the striatum to the hypothalamic units. The finding that caudate lesions did not change the results of interaction between the globus pallidus and sensory stimuli would indicate that the caudate does not have any important modulatory effects on pallidal influences on the posterior hypothalamic units. The role of the midbrain in caudate inhibition was tested in view of reports that facilitatory caudate phenomena in the cortex were abolished by mesencephalic reticular formation lesions 6 and that the inhibitory effect of the caudate on the amygdalo-hippocampal conduction was diminished or abolished in the cerveau isol~ preparation 19. In the present experiments, partial or total severance of the midbrain reduced the total percentage of responsive units following caudate and sensory interaction, but did not modify in this preparation the predominant percentage of units inhibited by caudate stimulation. This would suggest that while the globus pallidus lesions affected not only the percentage of responsive units but also the mode of their responsiveness to peripheral stimuli, the brainstem lesions only eliminated certain inhibitory pathways. These results are in accordance with previous proposals that the site of action of caudate inhibition may be at subcortical levels, as caudate inhibition was demonstrated on units in the ventromedian reticular formation of the brain stem 17 and, the interaction of pallidal and sciatic stimuli reduced the firing rate of dorsal tegmental units in cats, in relation to sciatic stimulation alone 1. In view of the abovementioned results and the close connections between the reticular formation and the posterior hypothalamus 2°, it is evident that multiple pathways may be involved in the striatal inhibitory effects on the electrical activity of the hypothalamus and consequently on its various regulatory functions.

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416

S. FELDMANAND N. DAFNY

SUMMARY

The effects of caudate nucleus or globus pallidus stimulation and lesions on the responsiveness of single cells in the posterior hypothalamus to photic, acoustic and sciatic stimulation, were studied in cats. The interaction between a conditioning caudate or pallidal and a sensory stimulus at an interval of 25 msec, caused prolonged inhibition in the firing rate of the majority of the units. In the case of the caudate nucleus, this inhibition was more marked in the first 1000 msec, while following globus pallidus stimulation it was sustained throughout the whole 2000 msec, after stimulation. The changes in the firing rate were accompanied by alterations in the pattern of the compound histograms of the units, which were different with caudatal and pallidal stimulation. Chronic lesions of the caudate nucleus did not change the percentage of responsive units, however they caused a considerable increase in the overall firing rate. Pallidal lesions reduced the number of responsive cells to sensory stimulation, but they have increased the percentage of cells facilitated by peripheral stimuli. Though pallidal lesions reduced the overall interaction between the three sensory modalities and the caudate nucleus, a considerable percentage of the responsive cells were facilitated by caudate stimulation, indicating that the presence of the globus pallidus exerted a strong inhibitory effect. Reticular formation lesions or transection of the midbrain have reduced the inhibitory effects of the caudate nucleus on the hypothalamic units. The possible striatal pathways and influences modulating the sensory input into the hypothalamus are discussed. ACKNOWLEDGEMENTS

The technical assistance of Mr. N. Conforti is gratefully acknowledged. This investigation has been aided by Agreement No. 4X5108 with the National Institutes of Health, Bethesda, Md., U.S.A.

REFERENCES 1 ADEY, W. R., BUCHWALD,N. A., AND LINDSLEY, D. F., Amygdaloid, pallidal and peripheral influences on mesencephalic unit firing patterns with reference to mechanisms of tremor, Electroenceph, clin. Neurophysiol., 12 (1960) 21~10. 2 BENITA, M., ET KRAUTHAMER, G., Blocage par le froid de Faction inhibitrice des corps stri6s, J. Physiol. (Paris), 58 (1966) 205. 3 BUSER, P., Subcortical controls of pyramidal activity. In D. P. PURPURA AND M. D. YAHR (Eds.), The Thalamus, Columbia Univ. Press, New York and London, 1966, pp. 323 347. 4 DAFNY, N., BENTAL, E., AND FELDMAN, S., Effect of sensory stimuli on single unit activity in the posterior hypothalamus, Electroenceph. clin. Neurophysiol., 19 (1965) 256-263. 5 DAI-NY, N., AND FELDMAN, S., Effects of caudate nucleus stimulation and lesions on single cell activity in the anterior hypothalamus, Electroenceph. clin. Neurophysiol., 23 (1967) 546-557. 6 DEMETRESCU,M,, AND DEMETRESCU, M., The inhibitory action of the caudate nucleus in cortical primary receiving areas in the cat, Electroenceph. clin. Neurophysiol., 14 (1962) 37 52.

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7 FELDMAN, S., Neurophysiological mechanisms modifying afferent hypothalamo-hippocampal conduction, Exp. Neurol., 5 0962) 269-291. 8 FELDMAN,S., Effects of reticular formation lesions on afferent projections to the hypothalamus, Electroenceph. clin. Neurophysiol., 15 (1963) 672 682. 9 EELDMAN,S., Visual projections to the hypothalamus and preoptic area, Ann. N.Y. Acad. Sci., 117 (1964) 53-68. 10 [SELDMAN,S., Striatal connections and influences on somatosensory and photic projections to the hypothalamus, Electroenceph. clin. Neurophysiol., 21 (1966) 249-260. 11 FELDMAN,S., VAN DER HE1DE, C., AND PORTER, R. W., Evoked potentials in the hypothalamus, Amer. J. Physiol., 196 (1959) 1163-1167. 12 EELDMAN, S., AND DAFNY, N., Acoustic responses in the hypothalamus, Electroenceph. clin. Neurophysiol., 25 (1968) 150-159. 13 FELTZ, P., KRAUTHAMER,G., AND ALBE-FESSARD,D., Neurons of the medial diencephalon. 1 Somatosensory responses and caudate inhibition, J. Neurophysiol., 30 (1967) 55-80. 14 Fox, S., AND O'BRIEN, J. H., Inhibition and facilitation of afferent information by the caudate nucleus, Science, 137 (1962) 423~J,25. 15 JASPER, H. H., AND AJMONE MARSAN, C., A Stereotaxic Atlas of the Diencephalon of the Cat, Nat. Res. Council of Canada, Ottawa, 1954. 16 JOHNSON,T. N., AND CLEMENTE,C. D., An experimental study of the fiber connections between the putamen, globus pallidus, ventral thalamus, and midbrain tegmentum in cat, J. eomp. Neurol., 113 (1959) 83-101. 17 KRAUTHA~ER, G., AND AEBE-FESSARD,D., Electrophysiologic studies of the basal ganglia and striopallidal inhibition of non-specific afferent activity, Neuropsychologia, 2 (1964) 73-83. 18 KRAUTHAMER,G., AND ALBE-FESSARD,D., Inhibition of nonspecific sensory activities following striopallidal and capsular stimulation, J. NeurophysioL, 28 (1965) 100-124. 19 KREINDLER,A., AND STRUNGARU,G., The influence of caudate nucleus on the activity of the amygdalo-hippocampic circuit, Proc. nat. Conf. Physiol., Bucharest, 1967, pp. 104-105. 20 NAUTA, W. J. H., AND KUYPERS, H. G. J,, Some ascending pathways in the brain stem reticular formation. In H. H. JASPER,L. D. PROCTOR,R. S. KNIGHTON,W. C. NOSHAYAND R. T. COSTELLO (Eds.), Reticular Formation of the Brain, Little, Brown, Boston, 1958, pp. 3-30. 21 NAUTA, W. J. H., AND MEHLER, W. R.., Projections of the lentiform nucleus in the monkey, Brain Research, l (1966) 3 4 2 . 22 VONEIDA,T. J., An experimental study of the course and destination of fibers arising in the head of the caudate nucleus in the cat and monkey, J. eomp. Neurol., l l5 0960) 75-87.

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