Development from primary to augmenting responses in the somatosensory system

Brain Research, 205 (1981) 49-66 © Elsevier/North-HollandBiomedicalPress

49

DEVELOPMENT FROM PRIMARY TO AUGMENTING RESPONSES IN THE SOMATOSENSORY SYSTEM

DIANE MORIN and MIRCEA STERIADE Laboratoire de Neurophysiologie, Ddpartement de Physiologie, Facultd de Mddecine, Universitd Laval, Qudbec G1K 7P4 (Canada)

(Accepted May 1st, 1980) Key words: SI cortex -- primaryresponses -- augmentingresponses

SUMMARY The development from primary to augmenting responses of somatosensory (SI) cortical area to low-frequency stimulation of the ventrobasal (VB) thalamus or white matter (WM) beneath SI in VB-lesioned preparations was studied by field potential analysis and extracellular unit recording. Compared to the major postsynaptic components of the primary field response, which reverse at 0.25-0.35 mm and whose sink extends from 0.6 to 1.8 ram, the augmenting potential reverses more superficially (0.1-0.15 ram) and its large depth-negativity is located in layers III and IV (0.4-1 ram). Augmentation is visible by the second shock of a 10/sec train; it grows from a late (I 5-20 msec) depth-negative wave in conjunction with the decrement of the early rapid components of the primary response. Out of 47 neurons that responded to the first shock in the 10/sec VB or WM train with early ( < 5 msec) discharges, 23 fulfilled stringent criteria for augmentation at the second shock: > 100 ~ increased discharge probability and > 100 ~ increased mean latency of response. The necessary condition for the generation of an augmented potential is a given temporal relation between the evoking stimulus and the declining phase of inhibition or the onset of rebound in the preceding response. The augmented potential cannot appear if the stimulus is delivered following the rebound of the preceding response. Not only this finding, but the similarity between the depth-profiles of the rebound and augmenting potential suggest that the same elements are responsible for both events. While the patterns of augmenting responses to WM stimulation in VB-lesioned preparations differ slightly from thalamically evoked augmenting waves, the intrinsic cortical organization is sufficient for the development of a primary potential into augmenting responses.

50 INTRODUCTION Although apparently little can be added to the long series of studies that followed Dempsey and Morison's ~ description of incremental responses of the augmenting type, some questions of how primary thalamocortical responses develop into augmenting potentials remain unanswered. Unlike well-defined augmenting responses in motorl,10,1z, 16 and parietal association (anterior suprasylvian)12,17 cortices of cat, unconclusive results were obtained in cortical somatosensory field responses to ventrobasal (VB) thalamic stimulation. Spencer and BrookharO 6 reported clear-cut augmenting potentials around the postcruciate dimple evoked by stimulation of ventralis posterolateralis (VPL) nucleus, but they recorded 'from a cortical zone outside of the primary receiving area', where 'augmenting responses are virtually uncontaminated by the primary response' (p. 29). Sasaki and his colleagues 8, 11 recorded primary thalamocortical field responses in the somatosensory area (SI), but 'mostly failed to elicit any responses of incremental nature'; the primary response was 'almost unchanged in configuration and reduced in amplitude upon low frequency stimulation 's (p. 660). The first aim of our analysis was to determine whether the development of augmenting responses depends on variations in the time-course of the excitatory-inhibitory sequence elicited by a preceding volley within a low-frequency stimulus train. The field and unit analysis of the primary response was, therefore, the first step to the study of augmenting responses evoked by subsequent shocks. A companion paper TM describes reticular-induced alterations of the time-course of the primary cortical response, with consequent changes in the development of augmenting responses. The second aim of the present study was to determine if thalamic mechanisms are essential in cortical augmentation or if the intrinsic cortical organization permit the development of augmenting waves. Surface potential studies are contradictory in this respect. Initially, cortical augmenting responses to stimulation of the internal capsule failed to occur in thalamectomized preparations, in spite of the integrity of the primary response 2. More recently, incremental potentials have been obtained in the motor cortex of animals with thalamic destruction, but they were closer to recruitment than to augmenting since the waves were predominantly surface-negative 14. We report here that although incremental patterns differ when stimulating the thalamus or the white matter, augmenting responses can be elicited in SI by stimulating corticipetal fibers in VB-lesioned preparations. METHODS Experiments were carried out on 20 enc6phale isol6 cats protected by infiltration of incised tissues and pressure points with a local anesthetic, paralyzed with gallamine triethiodide, and artificially ventilated. End-expiratory CO2 was maintained around 3.8 ~. Under these conditions, the EEG rhythms exhibited normal fluctuations between synchronized and desynchronized periods. The extracellular recording of unit discharge and focal slow waves was per-

51 formed with stainless-steel microelectrodes coated with platinum black (1-3/~m at the tip, impedances of 2-5 M ~ at 1 kHz). Microelectrodes were inserted perpendicular to the cortical surface, in points that were earlier established with silver balls to be the focus of a primary response with maximum amplitude to a VB shock. Fiber recordings (very brief, < 0.8 msec, exclusively positive discharges) were rejected. The depth was estimated from the combination of the micromanipulator depth with histological localization of small electrolytic lesions. Coaxial stimulating electrodes were inserted into the VB complex (middle part of the VPL) in 8 experiments, in both VB and white matter (WM) just beneath SI in 7 experiments, and in WM following complete electrolytic destruction of the VB complex in 5 experiments. Details on the method of simultaneouslyrecording focal slow waves and unit discharges, and on the extent of the VB lesion may be found in another paper from this laboratory ag. RESULTS

Field potential analysis of primary thalamocortical response The SI mass response to VB stimulation is highly similar to that of the visual cortex evoked by a synchronized afferent volley6. The numerals used in Fig. 1A indicate 5 components of the surface-response. As known from earlier works 6,9, the positive spike-like deflection 1, with peak latencies from 0.4 to 0.6 msec, reflects the activity in radiation axons as it does not undergo reversal and becomes steeper towards deeper layers. A depth-reversal of the surface-positive wavelet 2, which occurred at a peak latency of 1.1-1.2 msec, was difficult to detect in many instances, partly because this component was incorporated within the following larger negativity. However, in some descents, a small amplitude negative deflection, corresponding to the surface wavelet 2, became distinct at 0.5-0.7 ram, but then suddenly vanished; the participation of postsynaptic activity in the elaboration of this component was further suggested from superimposed recordings of synaptic discharges in a few neurons (see Fig. 2B). The major surface-positive waves 3 and 4, with peak latencies ranging from 1.8 to 2.2 msec and 2.9 to 3.4 msec, respectively, underwent distinct reversal. In 7 of the 8 descents used to plot the depth-distribution of the major postsynaptic components in Fig. IB, waves 3 reverses at a greater depth (mean: 0.345 mm) than wave 4 (mean: 0.225 mm). The differential behavior of these components at 0.15-0.3 mm is shown for a typical descent in Fig. 1A. Their amplitude gradually increased up to 1.3-1.6 mm below the pial surface, and then decreased with further penetration. With increasing stimulation strength, wave 4 became biphid; its late part, termed 4a in Fig. 2C, had a peak latency of 4-5 msec. The surface-negative wave 5, with a peak latency of 6-7 msec, reversed at a greater depth (mean: 0.4 mm) than earlier components.

Unitary events evoked by single shock stimulation A total of 125 neurons were synaptically modulated by single shock stimulation of VB and/or WM: 68 were excited at short ( < 6 msec) latencies, 6 at long (15-35 msec) latencies, while the spontaneous discharge of 51 units was suppressed without early excitation.

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Fig. 1 Depth-profile of early postsynaptic components of SI field response evoked by a single VB shock. i n this and all following figures, positivity is downwards. The evoked potential was recorded by the microelectrode at the cortical surface (S) and, then, at 0.05 mm steps up to 0.6 m m and at 0.1 m m steps up to 2.5 mm. In A, averaged responses (60 sweeps) at various cortical depths. Numerals 1 to 5 indicate the pre- and postsynaptic components of the primary VB-SI response (see text). The graph in B shows the depth distribution (vertical line in mm) of the two major surface-positive postsynaptic components (3 and 4) and of the subsequent surface-negative wave (5), resulting from averaging 8 descents in 6 different animals. In each descent, the maximal voltage of the depth-negative component 4 was considered to be 100 ~ , regardless of the depth at which this maximum was reached. All other measurements were computed as percentages of this maximal value.

Fig. 2F shows that the evoked discharge of the major neuronal group was superimposed on one of the principal postsynaptic field components: 3 (with latencies between 1.5 and 2.2 msec), 4 (2.5-3.2 msec) or 4a (3.5-5.2 msec). Ten units were modulated in relation with two (in one case with all three) of the depth-negative waves 3, 4 and 4a. Within the group related to more than one component of the field potential, 8 cells discharged on either wave 3 or wave 4 (or 4a), and 2 cells on either wave 4 or wave 4a (Fig. 2C, D). The depth-distribution of neurons driven by single VB shocks upon major field components 3 and 4 (including 4a) were examined. Fourteen of the 19 cells that discharged exclusively or prevalently on wave 3 were located between 0.4 and 1 mm from the surface (i.e. within layers III and IV), while 21 of 25 cells related to wave 4 (and 4a) were found below 1 mm (Fig. 2G). Only 4 units were excited by VB stimulation at latencies (0.9-1.3 msec) preceding the first major postsynaptic component 3, within the latency range of wavelet 2 of the

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Fig. 2. Relations between the synaptically evoked unit discharge and various components of field potential. A - E : 5 different cells. A: a neuron driven by VB stimulation at 0.9 msec; see lack of collision with a spontaneous discharge (arrow in l); this cell could follow 540/sec shocks, with a failure of response occurring only at the end of the shock-train (in 2) ; in 3, 50-sweep average of responses to the initial three shocks. B: VB-evoked excitation at a latency corresponding to field component 2. Numerals 3, 4 and 4a in B - D refer to major postsynaptic components of field response. C: increasing stimulation strength from 1 to 3 ; 10-sweep sequence in 4, with the same intensity as in 3, to show that evoked discharge was superimposed on either 3 or 4 field components. D : 1 and 2 same stimulation strength, but responses were recorded in periods with different (synchronization and desynchronization) EEG patterns. E : long latency (25-30 msec), high frequency ("~ 350/sec) repetitive discharge, in relation with a depth-positive slow wave (1 and 2, same intensity). F: histograms of units driven at short ( < 6 msec) and long (15-35 msec) latencies by VB and W M stimulation, in relation with components 3, 4 and 4a of field response; small letters indicate those units which were driven in relation with the two early components of the field response, such as neurons C and D (component 3 or 4, 3 or 4a, 4 or 4a; only unit b responded in relation with components 3 or 4 or 4a). Both neurons a and b driven by W M stimulation in relation with field components 3, 4 and 4a were recorded in a VB-lesioned animal. G : plotting the depth distribution of units (dots) synaptically excited (E) at latencies between 0.9 and 5 msec or inhibited (I) by VB stimulation.

54

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Fig. 3. Suppressed firing and rebound excitation. Single shocks to the VB (neurons A and B) or WM in VB-lesioned animals (neurons C and D). Dotted line in A approximately indicates the base line. B: evoked discharge (1) and 50-sweep dotgram (2; stimulus marked by vertical line) to show the subsequent period of suppressed firing and postinhibitory rebound. Vertical bar: 0.4 mV (same calibration: 0.5 mV in A and 2 mV in C). Neurons C and D (50-sweep dotgram, testing shock marked by vertical line) show firing suppression and rebound following WM stimulation in preparations with VB destruction. E: latency histograms of rebound (measured from the first discharge in the postinhibitory clustered excitation) following VB and WM stimulation; asterisks indicate those cells whose spontaneous discharge was suppressed without initial excitation; hatched parts in W M histogram indicate cells recorded in intact preparations, while all the other cells were recorded in VB-lesioned animals.

55 field potential (Fig. 2B). The remarkable ability of a neuron excited at the shortest latency (0.9 msec) to follow high-frequency (500/sec) VB shocks is depicted in Fig. 2A. We did not record units driven at latencies corresponding to the depth-positive components 5, i.e. between 6 and 15 msec. Four neurons modulated by VB at longer (20-35 rnsec) latencies discharged high-frequency repetitive spikes in relation with a long lasting, depth-positive wave (Fig. 2E), during which spontaneous firing of most single-spike discharging cells was suppressed. The early excitation elicited by a synchronized afferent volley was followed by a long period of suppressed firing associated with a depth-positive slow wave. This probably reflects the summation of hyperpolarizing potentials in the neighbouring cellular pool (Fig. 3A). In most (74 ~) neurons, the inhibitory period ended with a rebound excitation. This inhibitory-excitatory sequence could be induced by both VB (Fig. 3A, B) and WM stimulation in VB-lesioned preparations (Fig. 3C, D). The latency of VB- and WM-elicited rebound excitation (i.e. the onset of postinhibitory clustered discharge) is plotted in Fig. 3E. In 21 of 41 neurons the latency of the VBevoked rebound was between 130 and 150 msec. The peak latency of the VB-evoked depth-negative postinhibitory field potential is also between 130 and 150 msec (see arrows in Fig. 4C and in left column of Fig. 5). Of the 41 cells with rebound, 30 were located between 0.3 and 1.0 mm in depth. This corresponds to the region of maximal development of the late depth-negative field potential (see below, and Figs. 5 and 6). Of 11 cells whose spontaneous discharge was suppressed following VB stimulation without early excitation, none had rebound latencies shorter than 130 msec (asterisks in Fig. 3E). Rebound discharges induced by WM stimulation had longer latencies (median 190 msec) than following VB stimulation (median 150 msec) in both intact and VB-lesioned preparations.

Field potential analysis of augmenting response The primary VB-SI field response developed into typical augmenting potentials with 10/sec stimulation. By typical augmenting responses we mean initially and prevalently surface-positive (depth-negative) waves16 growing up from late depolarizing potentials 10. At the cortical surface, the early rapid postsynaptic components became much less distinct during 10/sec stimulation, but the duration of the whole surface-positivity doubled in spite of an unchanged presynaptic deflection (Fig. 4A). In depth-recordings, waxing was already visible on the second shock in a 10/sec train. Early components of primary response decremented simultaneous with the development of a long latency, high amplitude slow negative wave (Fig. 4B). The analysis of responses to paired shocks at different time-intervals indicated that an augmented potential cannot be generated if the testing stimulus is delivered after the depth-negative postinhibitory rebound o f the preceding response (Fig. 4C, D). The second stimulus elicited an augmented response when delivered 60-140 msec after the first stimulus, i.e. during the period of the declining phase of the preceding inhibition or the onset of the rebound component. It failed to elicit an augmenting potential when delivered after the peak of the rebound component, at intervals of 160-200 msec. In this case, a primary response was elicited.

56

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Fig. 4. Primary and augmented field response to VB stimulation. Fifty averaged sweeps. A: surface recording of responses evoked by 1/sec and 10/sec stimuli ; components 1 to 5 correspond to those already described in Fig. 1; note unchanged presynaptic deflection 1. B: another preparation; depth (0.7 ram) recording of the 1st, 2nd and 3rd response in a shock-train at 10/sec and, below, all responses; presynaptic component was not evident in this case; note, during augmentation, reduced amplitude of early postsynaptic rapid components and protracted duration of the slow negative wave. C and D : recordings in two different descents at 0.5 and 0.9 ram, respectively; in both cases, responses to single shocks (top traces) and to paired shocks separated by 60, 100, 140 and 180 msec. Rebound component (peak latency: 150 msec) indicated by arrow in C. See text.

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Fig. 5. Field potential analysis of VB-evoked augmenting response. Fifty averaged sweeps. Surface (S) and depth-recordings indicated in the middle are valid for all 4 columns. The two columns at left show the response evoked by a VB shock, and the responses to two 100 msec-delayed VB shocks (the interval between stimuli corresponds to a frequency, 10/sec, commonly used to elicit augmenting). The arrow in the left column indicates the postinhibitory depth-negative rebound component (peak latency: 130 msec). At right, the sweep was separately triggered for each of responses to the VB shock-pair, at higher gain and faster speed, to illustrate in detail the difference between the primary (1 st) and augmented (2nd) thalamocortical response. The depth-profile of the r e b o u n d c o m p o n e n t evoked by the first shock and the depth-profile of the augmenting response to the second shock in a 10/sec train are shown in Figs. 5 and 6. Three points are worth mentioning: (i) in contrast to the early postsynaptic deflections (see again Fig. 1), the late ( ~ 130 msec) depth-negative postinhibitory wave (arrow in Fig. 5) was barely recorded on the cortical surface even though it was higher in amplitude than the early depolarizing components; (ii) the defining c o m p o n e n t of the augmented response, i.e. the second surface-positive wave b (Fig. 5), had a dissimilar configuration and underwent distinct depth-reversal when c o m p a r e d to early depolarizing c o m p o n e n t s of the p r i m a r y response. At depths where the response was of maximal amplitude, b wave began at 6-8 msec, peaked at 15-20 msec, and had a duration of 28-35 msec. It reversed very superficially (0.1-0.15 m m )

58 and became a large negativity at a depth where the early depth-negative components 3 and 4 were only sketched (0.3 mm). In 6 descents, the ratio between the maximally developed depth-negativity and the corresponding surface-positivity was 2-4 for the early components of the primary response and 7-8 for the augmented response (Figs. 5 and 6); (iii) the surface-negative component (c) of the augmented response (peak latency at 30 msec) was reversed in polarity below 1.2 mm and turned into a huge positivity beyond this (Fig. 5). Unit responses in the transition from primary to augmenting responses The evoked discharge of 97 neurons was studied with single and repetitive (10/sec) VB and WM shocks. The different response evolutions from the first to the second (100 msec-delayed) stimulus, in various cellular types characterized in terms of the modulation induced by the 1st shock, are shown in Table I. We conservatively define an augmented unit response by > 100 % increased discharge probability and > 100 % increased mean latency of response. Within the major cellular type A, driven by the first VB shock with single discharge at a short ( < 5 msec) latency, half of the neurons fulfilled both criteria of augmentation. Fig. 7A shows a neuron which repetitively discharged with increasing latency on the crest of the augmented wave (from 2.5-3 msec in the first response to 15-25 msec in the second, 100 msec-delayed response). At interstimulus intervals over 140 msec, the augmented responses could no longer be elicited by the second shock. At 180 msec, the response to the second volley was of the primary type. This evolution is similar to that of field responses in Fig. 4C, D. The remaining half of type A neurons ,4-

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59 TABLE I Primary and augmenting unit responses to VB and W M stimulation VB

WM Intact VB

Lesioned VB

Total units (n = 97)

54

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driven by VB stimulation did not meet the criteria of augmentation: the response probability to the second stimulus did not exceed that to the first stimulus and the response latency did not increase by more than 30-50 ~, thus remaining within the time frame of early discharges ( < 5 msec). To understand the lack of augmentation in some VB-driven neurons, the temporal evolution of the response sequence to a single shock was studied in 12 of the I6 cells. (i) Seven neurons had an unusually short period of suppressed firing following the early excitation; consequently, the rebound had a latency between 60 and 100 msec (see these units in the latency histogram of VB-evoked rebound, Fig. 3E). The second stimulus in the 10/sec train thus arrived after completion of the inhib.itory-rebound sequence and, in concordance of data presented in Fig. 4C, D, could no longer elicit augmenting responses. (ii) Five neurons did not exhibit rebound following the period of suppressed firing. Fig. 7C shows one of the neurons lacking the discharge features of augmentation; the rebound component of the field response (peak latency: 70 msec) was completed before the following shock. Augmentation was also seen in the other two cellular types of Table I (B and C). However, because of their characteristics, both criteria of increased discharge probability and increased response latency do not apply to these groups. The probability of response to the following shocks at 10/sec increased in type B cells. However, the latency of repetitive discharge evoked by successive stimuli did not increase, approaching the peak of the augmented depth-negative slow wave (Fig. 7B). About 40 ~ of type C cells responded to the second and following 10/sec shocks with single or repetitive spikes superimposed upon the augmented field potential. The difference between the patterns of VB- and WM-evoked augmenting responses essentially consisted of a dissimilar ratio between the primary and secondary excitatory processes. Whereas thalamically elicited augmentation arose from the

60 selective enhancement of secondary depolarizing events associated with obliteration of primary components, the early excitation was generally preserved in WM-evoked augmentation. The response increment resulted from an additional excitation at a longer latency. Several data illustrate this difference. (i) The WM-evoked primary depth-negative field potential had a peak latency of 3-4 msec. The augmented response to the second stimulus added a smaller amplitude depth-negative wave with a latency of 10-15 msec without altering the primary component (Fig. 8A). In the case of the VBevoked augmented responses, the secondary excitatory component had a much greater

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Fig. 7. Augmenting patterns in different types of VB-modulated neurons. A: unit driven at short latency by the 1st stimulus (type A in Table I) and discharging repetitive spikes at longer latency during augmenting (2nd, 0.1 sec-delayed stimulus); below, 50-sweep averaged responses to the 2nd stimulus at time-intervals of 0.1, 0.14 and 0.18 sec; unit discharges (arrows) are seen in averaged field responses on the crest of the depth-negative wave at 0.1 sec and 0.14 msec time-intervals, but they are no longer evident at 0.18 msec when the response resumes the pattern of a primary type. B: unit discharging at a long latency (type B in Table I); superimpositions of unit discharges and field responses to the 1st, 2nd and 4th shocks in the 10/sec train and, below, 40-sweep dotgram of unit discharges to all five shocks in the 10/sec train. C: unit driven at short latency which did not exhibit augmenting patterns with 10/sec stimulation, thus preserving responses of primary type; note in this case that successive stimuli are delivered following completion of the rebound field component; compare to Fig. 4C, D.

61

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Fig. 8. Field and unit augmented responses evoked by VB and WM stimulation. A: 50-sweepaveraged field potentials evoked at cortical depth (1 ram) by two, 100 msec-delayed shocks to the VB and WM. Vertical bar, 0.6 mV. B: augmentation patterns of unit discharge induced by VB and WM stimulation. C: 50-sweep averaged responses to the 1st and 2nd WM shocks in a VB-lesioned preparation, and only the 2nd response at expanded sweep; a unit was simultaneously recorded with focal slow waves; evoked discharges are marked by arrows; dotted line approximately indicates the base line. amplitude than the primary one (see Figs. 5 and 6). (ii) During WM-evoked augmentation, the latency of the early discharge was preserved and followed by a distinct, secondary discharge (Fig. 8B). Augmenting responses could be obtained by W M stimulation in VB-lesioned preparations (Fig. 8C). The change from primary to augmented discharges during 10/sec VB stimulation, compared to the development of unit responses elicited by 10/sec W M stimulation in VB-lesioned preparations, is shown in the pooled poststimulus histograms of Fig. 9. (i) The discharge probability of the group excited at short ( < 5 msec) latencies by the first VB shock increased by 200 % from the first to the second and third response. Correspondingly, the mean latency of VB-evoked re-

62

sponses increased beyond 100 ~o between the first and following shocks. In the primary VB-evoked response, more than 80 ~ of the intervals were found in the bins between 0 and 4 msec. More than 80 ~ intervals of the second, augmented response were dispersed in the bins between 4 and 14 reset. In the primary WM-evoked response, almost 40 ~ of intervals were concentrated within the 2-4 msec bin, whereas about 7 5 ~ of intervals belonging to the augmented response were dispersed in the bins between 4 and 18 msec. It is noteworthy that, in variance with the VB-evoked Exc.

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b 20 3'o 4b 5'0 ms

Fig. 9. Poststimulus histograms of unit responses to the first three VB or W M shocks at 10/sec. Sixteen different neurons were analyzed: 8 excited (Exc.) at short latencies by the first VB (4) or W M (4) shock, and 8 whose spontaneous discharge was suppressed without early excitation (lnh.) by the first VB (4) or W M (4) shock. Each 2 msec-bin histogram was computed, on a bin-by-bin basis, from 4 individual histograms. Neurons tested with W M stimulation were recorded in VB-lesioned preparations. Symbols: S, shock number in the 10/sec train; R, per cent responsiveness (number of discharges to 100 shocks); X, mean latency; SD, standard deviation. Responsiveness (R) to the 1st shock in the group of inhibited (Inh.) cells represents, in fact, the co~Jnts of spontaneous discharge within the 50 msec following the testing stimulus.

63 response, the augmented response to the second WM shocks had two distinct peaks: an early, major one within the 4-6 msec bin, and a late, minor one within the 14-16 msec bin. These two peaks had the same latencies as the early and late components of the WM-evoked augmented field response in Fig. 8A (see comments above). (ii) Within the group whose spontaneous firing was inhibited by the first VB shock, the mode and mean latency (_~ 23 msec) of the augmented responses to following shocks were considerably longer when compared to the former group. The augmented responses to WM stimulation had shorter latencies than those to VB stimulation and, again, the probability of discharge was higher within the early peaks (8-10 msec bin versus the 16-20 msec bins). DISCUSSION The findings above show that the development of an augmenting thalamocortical potential in the SI area depends upon the temporal relation between the evoking stimulus and the late, inhibitory-rebound phases of the preceding response. Besides, we positively answer the question regarding the possibility of eliciting cortical augmenting responses in the absence of specific thalamic mechanisms. The cellular basis of the augmenting response was revealed by the intracellular investigations of Purpura et al. 1° and Creutzfeldt et al. 1 on motor cortical neurons driven by ventrolateral (VL) thalamic stimulation. According to these studies, the defining feature of augmentation is a marked increase in the magnitude of secondary excitatory postsynaptic potentials associated with attenuation of inhibitory postsynaptic potentials. Recordings of mass responses of the pyramidal tract 13 and intracellular studies on pyramidal tract neurons of the motor cortex 3 revealed that testing VL stimulation develops maximal augmentation when delivered at timeintervals of ---70-90 msec following a conditioning stimulus. These intervals correspond to the decline of the conditioning IPSP 3. The transition from primary to augmenting potentials in SI consists of the development of a secondary depth-negative focal wave (component b in Fig. 5) related to repetitive spikes occurring at longer latencies than the single discharge of the primary response (Fig. 7A). The only consistent difference between VL-driven and VB-driven augmenting potentials in respective cortical areas concerns the surfacenegative wave. Sasaki et al. 12 have defined the augmenting responses in anterior sigmoid cortex as consisting of a successive occurrence of 'deep' and 'superficial' thalamocortical potentials. At variance, the 'superficial' component of the incremental response in SI area lacks or, when present, it reverses in polarity deeper than in the motor cortex s (see also component c in the present Fig. 5). This difference led Sasaki and his colleagues8,11 to use the term of'sensory incremental response' for SI area (as distinct from augmenting potentials in motor and suprasylvian cortices) and to consider it a rather rare event. Since the surface-negative wave represents only a subordinate, recruiting component of augmenting potentials and since the augmenting waves can be clearly dissociated from the recruiting ones on the basis of an initial depthnegativity in laminar analysis, we consider that the similarities between augmenting patterns in motor and SI cortical areas are greater than the differences.

64 The depth-profile analysis revealed dissimilarities between the rapid postsynaptic components of the primary response and the augmented potential. The evolution of the latter at known depths within SI strikingly resembled that of the postinhibitory rebound wave (Fig. 6). As opposed to the primary response, whose sink extended roughly from 0.6 to 1.8 mm, the huge depth negativities of the rebound and augmenting waves were localized within layers III and IV (0.4-1 ram). Compared to the primary response, the augmented potential and rebound wave were less reflected at the cortical surface. Both these peculiarities suggest that the late depth-negative postinhibitory wave is mainly due to synchronous activation of local cells. These cells, as opposed to vertically oriented pyramidal-shaped neurons, mostly have radially oriented dendritic trees. Stellate cells in layer IV and the adjacent part of layer III of somatosensory cortex, with dendrites generally ramifying within the layer in which the soma lies, constitute up to 80 ~ of the present elements ~. Electrophysiological data corroborate the suggestion that local interneurons are primarily involved in the genesis of the postinhibitory rebound. Neurons discharging in high-frequency bursts, that were hypothesized as local circuit neurons in SI area 19, do selectively fire during the negative phase (corresponding to the rebound component) of the repetitive waves of the sensory afterdischarge; they do not discharge during the primary responseT. The similarity between the depth profile of the rebound wave and the augmented response in conjunction with the finding that the development of the latter is prevented, possibly by occlusion, after the completion of the former (Fig. 4C, D), lead to the possibility that the same elements are responsible for both events. Data from other cortical areas support this suggestion. Non-pyramidal neurons in the motor cortex exhibit a greater involvement than identified pyramidal tract cells in the mechanism underlying the generation of augmenting responses 1°. Putative interneurons in areas 5-7 were found to discharge spike barrages in close relation with the secondary depolarizing waves from which augmenting responses exclusively originate 17. These findings may help to explain the failure of Matsuda et al. 8 to find augmenting responses in SI with field potential analysis. VPL repetitive stimulation sometimes evoked 'sensory incrementing responses', a particular type of field potential which, in view of the short duration of the depth-negativity (= 12-13 msec) and of its latency peak (_~ 8-10 msec; both values computed by us after Fig. 6A, B in ref. 7), is closer to the primary than to the augmented response. These values, representing the duration and peak latency of the depth-negativity, are much shorter than those of the augmented depth-negativity in the present paper (duration: 28-35 msec; peak latency: 15-20 msec; see Fig. 5). In those experiments, both the primary and 'sensory incrementing' responses were reversed at the same cortical depths, which was not the case for the augmenting responses analyzed in the present work. Probably, the barbiturate anesthesia, used in the experiments by Matsuda et al. s, changed the timecourse of the whole series of excitatory-inhibitory-rebound events triggered by thalamic stimulation, with the consequence of preventing the development of augmenting while leaving intact the primary reponse. Li et al. 7 have indeed reported that at some levels of barbiturate anesthesia the rhythmic inhibitory-rebound sequences in the sensory afterdischarge are abolished while the primary response is still recordable;

65 this suggested that units related to the afterdischarge are different from those activated during the early response. The dependence of motor cortex augmenting responses on the integrity of the specific thalamus was previously suggested by changes from the first to the second, 0,1 sec-delayed response of VL units upon intranuclear stimulation: more intense firing, by more VL neurons, with slightly longer latency; and the number, grouping and timing of VL discharges reaching the cortex was regarded as sufficient to explain the similar features exhibited by cortical target elements 15. It is likely that a similar relation exists in the VB-SI system. Actually, the shorter median latency of the VBevoked rebound compared to that elicited by WM in VB-lesioned preparations (Fig. 3E) may well be due to the fact that, in the former case, VB units are rebounding following the local stimulation and, thus, contribute to a faster evolution of the inhibitory phase into the postinhibitory excitation of SI neurons. Also, the increase in percent responsiveness of unit firing is greater for the VB-elicited than for the WMelicited transition from the primary to the second, augmented potential (see the excited group in Fig. 9). While the VB probably contributes to cortical processes related to rebound and augmenting, the phenomena observed in SI neurons are obviously not a passive reflection of VB events: clear-cut postinhibitory rebound (Fig. 3C) and augmenting (Fig. 8C) were elicited by WM stimulation in preparations with complete VB destruction. This indicates that intrinsic cortical circuitry may generate both the postinhibitory rebound and augmentation. The difference in augmenting patterns evoked by VB or by WM stimulation, consisting essentially of the relative preservation of the early excitation in both field and unit responses to WM stimulation, cannot be easily explained. What should be borne in mind is that stimulation beneath SI area does not affect only VB-fugal fibers, but also commisural and corticocortical systems among others. As far as the postinhibitory rebound is concerned, a laminar analysis in area 5 led to the conclusion that this component is generated following thalamic, but not transcallosal stimulation 5. Co-stimulation of a variety of fiber systems with dissimilar depth distributions and target elements in SI probably accounts for the type of cortical augmenting responses induced by WM stimulation. ACKNOWLEDGEMENTS This work was supported by the Medical Research Council of Canada (MT3689). We thank Prof. K. Sasaki for his helpful comments on the manuscript. Thanks are due to M. Cardinal, P. Gigu6re and D. Drolet. D. Morin was a graduate student and accomplished her M.Sc. in this laboratory.

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