A midbrain projection to the centre median nucleus of the thalamus. A neurophysiological study

BRAIN RESEARCH

63

A M I D B R A I N PROJECTION TO T H E C E N T R E MEDIAN NUCLEUS OF T H E T H A L A M U S . A N E U R O P H Y S I O L O G I C A L STUDY

CARL J. DILA

Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill Universit), Montreal, Que. (Canada) (Accepted July 1st, 1970)

INTRODUCTION

A bulbar relay in the extralemniscal pathway to the nucleus centre median (CM) of the thalamus has been recently described 8. Other authors had previously reported that peripheral stimulation evoked a slow potential in the reticular formation (RF) of the midbrain11, 21. The results of several anatomical studies suggest that neurons throughout the length of the brain stem, particularly those of the nuclei of the medial two-thirds of the reticular formation, contribute axons to the ascending reticular pathwayg,l°,22, ~6. It is now well established that this pathway divides at the mesencephalic-diencephalic junction, one portion taking a ventral route to the hypothalamus, the other ascending into the thalamus where it terminates within the intralaminar nucleiC2, 28. The present study tests the hypothesis that the midbrain RF is the origin of a projection to CM. This projection is demonstrated by means of CM evoked potential and unit response analysis and the brain stem pathways of the extralemniscal somatosensory system are discussed. MATERIALS AND METHODS

Experiments were performed on 16 adult cats of both sexes ranging in weight from 2.5 to 4.5 kg (median weight: 3.35 kg). All the experiments were 'acute', the longest ones lasting up to 20 h from the beginning of anesthesia. In half the experiments encdphale isol6 preparations were used and in the other half intravenous chloralose, 20-80 mg/kg (ref. 18), was given. In all cats ether inhalation was used for the induction of anesthesia and cannulation of the femoral vein and trachea. All pressure points were infiltrated with Novocaine 1 ~ (Winthrop) and the head was mounted in the stereotaxic frame. A craniectomy was performed to permit insertion of stimulating and recording electrodes. All animals were paralyzed with intravenous Curare (tubocurarine chloride, Squibb) or Flaxedil (gallamine triethiodide, Poulenc) and ventilated with a respirator for the duration of the recording session. The rectal temperature was maintained at between 38 and 40°C with a heat lamp. Brain Research, 25 (1971) 63-74

64

;. J. I)ILA

The mesencephalic reticular formation was stimulated through bipolar Isonei insulated stainless steel needle electrodes. A single electrode of this pair was, oN occasion, used for recording of evoked potentials within the midbrain RF. Electrical stimulation to the midbrain R F was delivered by a constant-current stimulator (Nuclear-Chicago, Model 7t50 Series) using symmetrical, rectangular, biphasic pulses of 0.5 msec duration and 0.2-3.0 mA intensity 19. Electrical stimulation was delivered to the limbs with a Grass stimulator (Model 54) and stimulus isolation unit through a pair of No. 26 hypodermic needles inserted into the footpad ; pulses of 0.2 msec duration and 2.0-12.0 V intensity were used. Both the central and peripheral stimuli were triggered by a 'synch-pulse' after a variable dcla3. Thalamic units and slow waves were recorded through a tungsten microelectrode 1~ through a common high impedance F E T preamplifier. The preamplifier output was then taken to separate system amplifiers* so that the units and the evoked potentials could be displayed independently. The signals from the thalamic units and slow wave and the RF slow wave were displayed on a Tektronix RM 565 dual beam oscilloscope and a Tektronix Type 564 storage oscilloscope. In addition to visual and photographic analysis the thalamic unit recordings were subjected to statistical analysis by the Mnemotron Computer of Average Transients (CAT). The CM was explored within the stereotaxic coordinates a7 frontal 7.0 or 7.5, lateral 2.5 to 3.5 and horizontal -I 1.0 to --2.0. Adjacent electrode tracks were always 1 m m apart. The stimulating electrodes were located within the RF of the midbrain at the stereotaxic coordinates frontal 3.0, lateral 3.0 and horizontal 0.0 to --2.0. All recording sites and most of the stimulation sites were verified anatomically. The statistical analysis of units subjected to single shock stimulation is based on the assumption that the spontaneous activity of these units may be described as a stationary, renewal, stochastic point process 20. The analysis most commonly perfo rmed on units subjected to single shock stimulation is the poststimulus-time histogram (PST histogram), which is essentially a cross-correlation between the train o f stimuli and the train of unit spikes. Unit responses to the stimulus are identified by significant departures from the expected constant value of a null cross-correlation histogram. Peaks in the PST histogram represent increased probability of unit firing l excitation or activation) and troughs represent decreased probability of firing (inhibition). In this study the responses of many of the units were clear-cut on inspection of the PST histogram. However, when the significance of a response was to any degree questionable, and in all the cases used for illustration, a null value histogram was constructed for the unit by introducing a fictitious series of stimuli throughout a portion of the record when no actual stimuli were presented. The actual PST histogram was compared with the null value histogram. The latency of early responses (activation) to stimulation was measured directly

* The custom-made amplifier was designed by Mr. D, Skuce and employed 4 solid state operational amplifiers (Philbrick Model P85 AU) to provide calibrated gains up to 100,000 and variable upper and lower roll-off frequencies. Brain Research, 25 (1971) 63-74

MIDBRAIN PROJECTION TO C M

65

19-7

0., mV m,.o

A

,oj_ 35

U

C

0L 4

30

500 msec

O

u

20-

O

z

15-

D 10-

,3

5 0-

....... --I 500 msec

0L

I ~

500 msec

Fig. 1. Activation inhibitio~activation response of a CM unit to stimulation of the ipsilateral midbrain RF. This unit exhibited a unique response of primary inhibition to stimulation of the contralateral forelimb. A, Initial activation response to reticular stimulation. B, Null histogram; in this and subsequent illustrations a histogram of the spontaneous activity is made using the same time scale and number of sweeps as were used in the PST histogram. Cornparison of the PST histogram with the null histogram indicates the statistical significance of the responses. C, PST histogram showing response to stimulation of the ipsilateral RF; the early activation is 'lost' in the stimulus artifact. D, PST histogram showing response to stimulation of the contralateral forelimb; the spikes in the first few bins following the stimulus artifact are spontaneous activity reflecting the latency of inhibition. Arrow in this and subsequent illustrations indicates the stimulus artifact. A, 5 sweeps; B-D, 99 sweeps. from the raw unit data displayed on a n oscilloscope screen by averaging the time of occurrence o f 5 consecutive responses to single shock stimulation. Response d u r a t i o n of both activation and i n h i b i t i o n was most easily measured from the PST histograms. A n a t t e m p t was made to show a correlation between unit responses and evoked potentials recorded simultaneously from the tungsten microelectrode. The unit activity and slow wave were c o m p a r e d by first o b t a i n i n g a display o f superimposed multiple sweeps on the storage oscilloscope screen. Later, the slow wave was averaged by the C A T and compared with the PST histogram of the unit recorded simultaneously12 14. The latter technique permits the storage and s u m m a t i o n of much larger quantities o f data, thus e n h a n c i n g the statistical significance o f the observations. The results obtained from b o t h techniques, however, were in agreement. Brain Research, 25 (1971) 63 74

66

, . J.

I)]LA

RESULTS

Single shocks were delivered to the midbrain R F at the rate of 1/sec. Thethreshold intensity for the CM slow potential evoked by single shock stimulation of the midbrain R F was determined to be 0.4-0.5 mA and the intensity of stimulus required for an evoked CM potential of maximum amplitude was 1.5 mA using a rectangular biphasic pulse of 0.5 msec duration. For CM unit analysis a pulse of 1.5-3.0 m A intensity, 0.5 msec duration was used. Within the CM 89 units were observed for a period of time long enough to analyze the response to single shock stimulation of the midbrain RF. (Any neuron with a rapid, regular firing pattern was considered to be injured and was excluded from the study.) Of the 89 units analyzed 29 showed no significant change in firing pattern after single shock stimulation of the midbrain RF. Fifty-one neurons responded to single shock stimulation of the midbrain RF with activation. The latency for this response (Fig. 1A) was found to be between 2 and 12 msec (mean latency -- 7.2 msec) in 45 units: another 6 units had an activation latency of 18-100 msec (mean ~ 25 msec). Inhibition. following the initial activation. was seen in 32 units. The duration of the period of inhibition ranged from 10 to 225 msec (mean duration -- 69 msec). Further. in a number of units late activation occurred as a secondary event, following the initial activation-inhibition sequencc (Fig. 1C). Primary inhibition following single shock stimulation of the midbrain RF was seen in 9 units. In these cases the period of inhibition lasted from 20 to 150 msec (mean duration 65 msec). A period of activation followed the primary inhibition in 6 of 9 units. A total of 17 CM units were studied with single shock electrical stimulation of the limbs under conditions o f light chloratose anesthesia. Ten of 17 units responded to peripheral stimulation. In 9 of the responsive units a pattern of activation was seen (Fig. 3A. C); one unit exhibited primary inhibition with peripheral stimulation (Fig. 1D). All the responsive units responded to electrical stimulation of more than one limb. Further, all the units which responded with activation to electrical stimulation of the limbs also responded in a similar manner to natural stimulation of two or more limbs. The effective natural stimulus was a pin-prick or a brusque tap delivered manually with a pencil as described by Bowsher e t al. 8. The latency from electrical stimulus (contralateral forelimb) to first spike was between 18 and 40 msec (mean latency = 24.2 msec) for the 10 units which exhibited activation. Thirteen of the 17 units studied with peripheral stimulation were also tested with single shock stimulation of the midbrain RF. Eight units were affected alike by peripheral and RF stimulation, that is they were either activated (4 units) or they showed no response (4 units) to both peripheral and RF stimulation. Five units were affected differently by the two types of stimulation 4 being responsive to one but not to the other and one unit being activated by peripheral stimulation but showing primary inhibition with RF stimulation. Slow potentials were evoked in the midbrain RF, in the region of nucleus subBrain Research, 25 ~1971) 63-74

67

MIDBRAIN PROJECTION TO C M

cuneiformis 32, and in CM by electrical stimulation of the limbs and in CM by elettrical stimulation of the midbrain RF. As in the case of the CM units which responded to electrical stimulation of the limbs, the natural stimuli capable of evoking a slow potential in the midbrain RF and the CM were pin-prick and a brusque mechanical tap. Within the CM both peripheral and midbrain RF stimulation evoked an identical slow wave. The CM evoked potential was found at the stereotaxic coordinates frontal 7.0 and 7.5, lateral 3.0 and 3.5, horizontal + 2 to --1.0. The CM slow wave was usually an initially negative biphasic or triphasic potential with a duration of 100-120 msec. The latency of the CM slow wave was 4 msec for stimuli delivered to either side of the midbrain RF. For peripheral stimuli the latencies were contralateral forelimb: 17 msec; ipsilateral forelimb: 22 msec; contralateral hindlimb: 24 msec; ipsilateral hindlimb: 25 msec. 11-5

B

A z

500 msec, 0.1mVJ 5msec

C E

d c;

z

0"

0.2 mV~J 20 msec

D

500 msec Fig. 2. Correlation of unit activity with evoked potential recorded simultaneously in CM. A, Short latency response to stimulation of the ipsilateral RF. B, Null histogram. C, PST histogram ; the early response is 'lost' in the stimulus artifact (arrow) due to the relatively long analysis time. D, CAT averaged evoked potential showing correlation of the initial negative and positive components with unit activation and inhibition, respectively. E, Storage oscilloscope display of superimposed unit activity (99 sweeps) and slow wave (10 sweeps). A, 5 sweeps; B and C, 99 sweeps; D, 40 sweeps. Brain Research, 25 (1971) 63-74

68

~. L

t)11.~

18-10

4. L u . m w ~

B

-I

0.2 mY

4.

500 msec

C

100-

75

500 msec

1:[ U

-

"6 -r

0 500 msec

50

-

6

Z

25ul

i,0r

G

0500 msec

500 msec

Pig. 3. U n i t - s l o w wave response correlation. A - C . Contralateral forelimb stimulus. D - F , lpsilaterat

RF stimulus. G, Null histogram. A. D, Early unit response (upper trace) and simultaneous evoked potential. B. E. Averaged evoked potential. C, F. PST histograms of unit activity. A, Do 5 sweeps; B, E. 50 sweeps; C, F and G, 99 sweeps. See discussion m text. In all cases it was seen that the early negative c o m p o n e n t o f the slow wave, when present, corresponded to a period o f neuronal activation (Fig. 2). Frequently. the initial unit activation phase was not associated with a negative deflection of the slow wave response (Fig. 3D, E). This m a y be due to cancellation o f the initial negativity by concurrently developed positivity. Further, the early negative c o m p o n e n t o f the slow wave response m a y be relatively variable in its phase-locking with the stimulus and thus be cancelled in the averaging process. T h e positive c o m p o n e n t o f the evoked potential was less clearly associated with unit inhibition. A l t h o u g h the PST histogram usually showed a period o f inhibition following the initial activation, the time o f Brain Research, 25 (1971) 63-74

MIDBRA1N PROJECTION TO c m

69

occurrence of the inhibitory response did not coincide precisely with slow wave positivity. Often, the slow wave c o m p o n e n t was seen to occur somewhat earlier than the unit response (Fig. 3). Thus, although the evoked slow wave seems to enable one to predict the relative magnitude, d u r a t i o n and sequence of the activation and inhibition of neuronal activity, the precise temporal parameters of the unit response are known only by direct observation. Using the classic methods of facilitation and occlusion of the evoked potential, convergence of peripheral and m i d b r a i n R F stimuli was demonstrated within the C M (Fig. 4). The area u n d e r the slow wave is the i m p o r t a n t parameter in the d e m o n s t r a t i o n of facilitation and occlusion in multisynaptic pathways such as the spinoreticular and reticulothalamic systems 2v. In the present experiments inspection of the evoked potentials revealed obvious facilitation and occlusion, and actual m e a s u r e m e n t of the areas of the slow waves was not necessary to demonstrate the two p h e n o m e n a .

D-13

A

D

/ i,

A

C

l

A v

A A

A

0.4 m V I 50

rnsec.

Fig. 4. Convergence of hindlimb spinoreticulothalamic pathway and midbrain RF projection in CM. A-C, Facilitation using threshold stimuli; the area under the slow wave in C is greater than the sum of the slow waves in A and B. D F, Occlusion using 3 times threshold stimuli; the area under the slow wave in F is less than the sum of the slow waves in D and E. Stimulus delivered to contralateral hindlimb in A and D, to ipsilateral RF in B and E and to both with a 35 msec interval between stimuli in C and F. Brain Research, 25 (1971) 63-74

70

~-..!. 1)1[. ,.~

DISCUSSION

Reticulothalamic pathways

The characteristics and parameters of the slow potential evoked in CM by stimulation of the limbs a,4,1s, the RF 31. and the cortex 2 have been well documented. In the present study these findings have been confirmed and attention is directed to the problem of extralemniscal pathways. Estimates of the conduction velocity over the spinoreticulothalamic pathway have been made using the method described in detail by Albe-Fessard and Kruger 3. The data in the present study yield a value of approximately 36 m~sec for the spinal segment of the spinoreticular pathway. Applying the same procedure to the CM potential evoked by limb stimulation yields a conduction velocity of approximately 31 m/sec for the spinal segment of the spinoreticulothalamic pathway. These values are clearly consistent with conduction over a pathway composed of small myetinated fibers (group II1) za. Similar values for spinoreticular conduction velocities have been reported by other investigators 1,'~. The conduction velocity of the reticulothalamic segment (midbrain RF to CM may be calculated from the latency of the CM potential evoked by midbrain RF stimulation, 4 msec. and the distance between stimulating (midbrain RF) and recording (CM) electrodes. 4 ram. The conduction velocity is thus approximately 1.0 mjsec for the tel iculothalamic segment of this ascending pathway. Even by using the shortest latency for the CM unit activation produced by midbrain RF stimulation. 2 msec. a conduction velocity of only about 2 m/see is calculated. The study of Bowsher et al. ~ reports a 2 msec latency for the slow wave evoked in CM by stimulation of the bulbar RF; since the distance traveled by this impulse is about 15 mm the conduction velocity is approximately 7.5 m sec for the reticulothalamic course of this pathway. This slowing of the afferent impulse within the brain stem, although considerable, is not, obviously, of the same magnitude as that reported in the present study. However, in either case. the slowing of the impulse must be accounted for by smaller nerve fibers and/or polysynaptic transmission 16,2s. Anatomical studies show that there are two pathways for the ascending reticular impulses2'~; these pathways are separated in the lower brain stem but become intermingled as the ascending reticular system reaches midbrain levels. The nucleus gigantocellutaris of the medulla has been shown by Bowsher et al. s to be an important relay of the spinoreticutothalamic pathway which transmits the impulses responsible for the CM potential evoked by limb stimulation. The lateral parvocellular reglon of the caudal brain stem is the relay for a smaller group of spinoreticular and lateral spinothalamic tract fibers, some of which terminate in the midbrain RF (nucleus subcuneiformis) which in turn contributes axons to the final segment of this spinoreticulothalamic pathway z2. This minor segment is probably the anatomic pathway of the slow potential evoked in the midbrain R F by limb stimulation 21 In spite of the anatomical data pointing to two separate pathways in the ascending reticular system, the physiological data in the present study must be interpreted Brain Research. 25 ( 1971 ) 6 3 - 7 4

MIDBRAIN PROJECTION TO

CM

71

cautiously. It is recognized that the two pathways so clearly seen in more caudal brain stem structures become intermingled at midbrain levels. Thus a stimulus delivered to the midbrain RF (nucleus subcuneiformis) might be activating passing fibers of the central tegmental tract which originated in the 'bulbar relay' to CM, the nucleus gigantocellularis of the medulla, in effect stimulating the same spinoreticulothalamic pathway at a higher level. The evidence of the present data supports the interpretation that the converging extralemniscal impulses to CM are mediated by two separate pathways, but this cannot be considered as proven. The evoked potential in nucleus subcuneiformis, the site of the midbrain stimulation, implies a synaptic event mediated by the minor, lateral ascending reticular pathway of the spinoreticular system 21,~2. The CM slow potential evoked by stimulation of this region appears to be mediated by postsynaptic elements (neurons of nucleus subcuneiformis) rather than passing fibers from nucleus gigantocellularis. Several units showed different responses to midbrain stimulation on the one hand and to peripheral stimulation on the other. These responses, although different, are within the limits of what might be predicted from analysis of the slow' wave response. These unit responses are not easily explained in terms of stimuli delivered to the same pathway at different loci. Finally, the difference between the reticulothalamic conduction velocity, reported here for the midbrain projection to CM and that calculated from the data of Bowsher and his colleagues s for the bulbar relay to CM, suggests that two separate pathways convey extralemniscal somatosensory impulses to the CM. C M unit responses

From the data in the present study certain generalizations concerning the responses of CM units can be made. To both peripheral and midbrain reticular stimulation over half the units observed exhibited a response pattern of activation inhibition or primary inhibition. These observations apply to units with established spontaneous spike activity, in both unanesthetized cats (enc6phale isol6) in which responses to RF stimulation were studied, and cats anesthetized with light doses of chloralose in which responses to peripheral stimulation were studied. Thus, 67 ~o of responsive units showed some inhibition as a consequence of the stimulus delivered to the midbrain RF, and 7 of l0 units responding to peripheral stimulation also exhibited a pattern of activation-inhibition. Albe-Fessard and Gillet 2 also concluded that inhibition is an important factor in CM unit responses; however, in their study of CM unit responses to peripheral stimulation Albe-Fessard and Kruger 3 reported inhibition in only 11 of 181 responsive units. They raised the possibility that some of these units may have been injured, making interpretation of their data on inhibition difficult. Bowsher et al. s, discussing these results, suggest that the proportion of units inhibited by peripheral stimulation decreases rostrally through the reticular formation and centre median. However, the effect of chloralose anesthesia in earlier studies2,3, s, 'silencing' the spontaneous activity of CM units, may have masked the inhibition which in the present work is an important part of the CM unit response. Brain Research, 25 (1971) 63 74

72

~ J. t)lt_,~

The significance of inhibition of CM units in response to both peripheral and midbrain RF stimulation is underscored by comparison of the evoked stow potential with unit activity. The most prominent feature of the CM evoked potential is the positive component. The earlier negative component associated with unit activation was variable in its appearance. The negative component of the evoked potential reflects an excitatory input, a summation of EPSPs within the neuron pool: the positive component arises from summation of inhibitory synaptic potentialsZ4, ea. Thus, the slow wave response in CM seems to confirm the observation of the unit activation inhibition sequence although, as noted above, the temporal courses of unit responses and evoked potential components are not simultaneous. The present data are insuf ficient to indicate exactly what inhibitory mechanism is operating in CM. It is possible that this is postsynaptic inhibitionS-V; however, whether this inhibition is mediated by local interneurons or by a long chain negative feedback loop~9, a0 cannot be ascertained. SUMMARY

A midbrain projection to the CM arising in the region of the nucleus subcuneiformis is demonstrated by CM unit responses and the CM slow potential evoked by midbrain RF stimulation. The spinoreticulothalamic (via the 'bulbar relay') pathway and the midbrain reticulothalamic pathway converge upon common neural elements in CM as demonstrated by the facilitation and occlusion of the evoked potential. The evidence suggests that the converging impulses are mediated by two separate ascending reticular pathways. Inhibition is a prominent feature of CM unit responses to single shock stimulation of both the midbrain RF and the limbs. Inhibition was seen in 67 ~ of units which responded to stimulation of the midbrain RF. The most common unit response pattern seen was initial activation followed by inhibition; the data are insufficient to determine the precise mechanism operating in the neuronal inhibition. ACKNOWLEDGEMENTS

The research reported here formed the basis of a thesis submitted to the Faculty of Graduate Studies and Research, McGill University, in partial fulfillment of the requirements for the degree of Master of Science. The project was directed by Professor Pierre Gloor, whose advice and criticism were a source of constant encouragement. The investigator was supported by the National Institute of Neurological Diseases and Blindness, U.S. Public Health Service, Training Grant 2 Ti NB 516i-1 t, 12. This grant is administered by Dr. Francis L. McNaughton, whose generosity and cooperation are gratefully acknowledged, The project was supported by the Medical Research Council o f Canada, Operating Grant MT-3140.

Brain Research, 25 (1971) 63-74

MIDBRAIN PROJECTION TO

CM

73

REFERENCES I ALBE-FESSARD, D., Organization of somatic central projections. In W. D. NEFF (Ed.), Contribu-

tions to Sensory Physiology, Vol. 2, Academic Press, New York, 1967, pp. 101-167. 2 ALBE-FEsSARD, D., ET GILLET, E., Convergences d'afferences d'origine corticale et p6riph6rique vers le centre m6dian du chat anesth6sie ou 6veill6., Electroenceph. clin. Neurophysiol., 13 (1961) 257 269. 3 ALBE-FESSARD, D., AND KRUGER, L., Duality of unit discharges from cat centrum medianum in response to natural and electrical stimulation, J. Neurophysiol., 25 (1962) 3-20. 4 ALBE-FEssARD, D., ET ROUGEUL, A., Activit6s d'origine somesth6sique 6voqu6es sur le cortex nonsp6cifique du chat anesth6si6 au chloralose: r61e du centre m6dian du thalamus, Electroenceph. clin. Neurophysiol., 10 (1958) 131-152. 5 ANDERSEN, P., Rhythmic 10 per sec activity in the thalamus. In D. PURPURA AND M. YAHR (Eds.), The Thalamus, Columbia Univ. Press, New York, 1966, pp. 143-151. 6 ANDERSEN, P., AND ECCLES, J. C., Inhibitory phasing of neuronal discharge, Nature (Lond.), 196 (1962) 645-647. 7 ANDERSEN, P., AND SEARS, T. A., The role of inhibition in the phasing of spontaneous thalamocortical discharge, J. Physiol. (Lond.), 173 (1964) 459-480. 8 BOWSHER, D., MALLART, A., PETIT, D., AND ALBE-FESSARD, D., A bulbar relay to the centre median, J. Neurophysiol., 31 (1968) 288-300. 9 ~RODAL, A,, The Reticular Formation of the Brainstem. Anatomical Aspects and Functional Correlations, Oliver and Boyd, Edinburgh, 1957, pp. 23 29. l0 BRODAL, A., AND ROSSI, G., Ascending fibers in brainstem reticular formation of the cat, Arch. Neurol. Psychiat. (Chic.), 74 (1955) 68-87. 11 COLLINS, W., AND O'LEARY, J., Study of a somatic evoked response and midbrain reticular substance, Electroenceph. clin. Neurophysiol., 6 (1954)619-628. 12 DREIFUSS, J. J., MURPHY, J. T., AND GLOOR, P., Contrasting effects of two identified amygdaloid efferent pathways on single hypothalamic neurons, J. Neurophysiol., 31 (1967) 237 248. 13 Fox, S. S., AND O'BRIEN, J. H., Duplication of the evoked potential waveform by curve of probability of firing of a single cell, Science, 147 (1965) 888-890. 14 GERSTEIN, G. L., Neuron firing patterns and the slow potentials, Electroenceph. olin. Neurophysiol., 20 (1961) 68-71. 15 HUBEL, D., Tungsten microelectrodes for recording from single units, Science, 125 (1957) 549 550. 16 JASPER, H., Recent advances in our understanding of ascending activities of the reticular system. In H. JASPER, L. PROCTOR, R. KNIGHTON, W. NOSHAY AND R. COSTELLO (Eds.), Reticular Formalion of the Brain, Little, Brown, and Co., Boston, 1958, pp. 319 331. 17 JASPER, H., AND AJMONE MARSAN, C., A Stereotaxic Atlas of the Diencephalon of the Cat, The National Research Council of Canada, Ottawa, 1954. 18 KRUGER, L., AND ALBE-FESSARD, D., Distribution of responses to somatic afferent stimuli in the diencephalon of the cat under chloralose anesthesia, Exp. Neurol., 2 (1960) 442-467. [ 9 LILLY, J. C., Injury and excitation by electric currents. In D. E. SHEER fed.), Electrical Stimulation t~/'the Brain, Univ. Texas Press, Austin, 1961, pp. 60 66. 20 MOORE, G. P., PERKEL, D. H., Ar,D SEGUNDO, J. P., Statistical analysis and functional interpretation of neuronal spike data, Ann. Rev. Physiol., 28 (1966) 493-522. 21 MoroN, F., Afferent projections to the midbrain tegmentum and their spinal course, Amer. J. Physiol., 172 (1953) 483-496. 22 NAUTA, W., AND KUYPERS, H., Some ascending pathways in the brain stem reticular formation. In H. JASPER, L. PROCTOR, R. KNIGIOTON, W. NOSHAY AND R. COSTELLO, (Eds.) Reticular Formation of the Brain, Little, Brown, and Co., Boston, 1958, pp. 3 30. 23 POMPEIANO,O., AND SWETT, J., Identification of cutaneous and muscular afferent fibers producing EEG synchronization or arousal in normal cats, Arch. ital. Biol., 100 (1962) 343-380. 24 RALL, W., Theoretical significance of dendritic trees for neuronal input output relations. In R. F. REISS (Ed.), Neural Theory and Modeling, Stanford Univ. Press, Palo Alto, 1964, pp. 73-97. 25 RALL, W., Distinguishing theoretical synaptic potentials computed for different soma-dendritic distributions of synaptic input, J. Neurophysiol., 30 (1967) 1138-1168. 26 Ross~, G., AND ZANCHETTI, A., The brainstem reticular formation. Anatomy and physiology, Arch. ital. Biol., 95 (1957) 199-435. 27 RucH, T. C., PATTON, H. D., WOODBURY, J. W., AND TOWE, A. L., Neurophysiology, Saunders, Philadelphia, 1965, p. 162. Brain Research, 25 ( 1971 ) 63-74

74

(:. J, DILA

28 SCHE1BEL, M., AND SCHEIBEL, A., Structural substrates for integrative patterns in the brainstenl reticular core. In H. JASPER, L. PROCTOR, P. KNIGHTON, W. NOSHA¥ AND R. COSTFL~:O (Eds.). Reticular Formation o f the Brain, Little, Brown, and Co., Boston, 1958, pp. 31-55. 29 SCHEIBEL, M., AND SCHEIBEL, A., The organization of the nucleus reticularis thalami. A Golgi study, Brain Research, 1 (1966) 43-62. 30 SCHEIBEL, M., AND SCHEIBEL,A., Structural organization of non-specific thalamic nuclei and their projection toward cortex, Brain Research, 6 (1967) 60-94. 31 STARZL, T., TAYLOR, C., Ar
Brain Research, 25 (1971) 63-74