Anesthetized Macaque Monkeys Research Articles

Loss of cerebral regulation during cardiac output variations in focal cerebral ischemia.

Focal cerebral ischemia was induced in anesthetized macaque monkeys by unilateral middle cerebral artery occlusion. The effect of blood volume expansion by a colloid agent and subsequent exsanguination to baseline cardiac output (CO) on local cerebral blood flow (CBF) was measured by the hydrogen clearance technique in both ischemic and nonischemic brain regions. Cardiac output was increased to maximum levels (159% +/- 92%, mean +/- standard error of the mean) by blood volume expansion with the colloid agent hetastarch, and was then reduced a similar amount (166% +/- 82%) by exsanguination during the ischemic period. Local CBF in ischemic brain regions varied directly with CO, with a correlation coefficient of 0.89 (% change CBF/% change CO), while CBF in nonischemic brain was not affected by upward or downward manipulations of CO. The difference in these responses between ischemic and nonischemic brain was highly significant (p less than 0.001). The results of this study show a profound loss of regulatory control in ischemic brain in response to alterations in CO, thereby suggesting that blood volume variations may cause significant changes in the intensity of ischemia. It is proposed that CO monitoring and manipulation may be vital for optimum care of patients with acute cerebral ischemia.

Neural responses to visual texture patterns in middle temporal area of the macaque monkey.

1. We studied how neurons in the middle temporal visual area (MT) of anesthetized macaque monkeys responded to textured and nontextured visual stimuli. Stimuli contained a central rectangular "figure" that was either uniform in luminance or consisted of an array of oriented line segments. The figure moved at constant velocity in one of four orthogonal directions. The region surrounding the figure was either uniform in luminance or contained a texture array (whose elements were identical or orthogonal in orientation to those of the figure), and it either was stationary or moved along with the figure. 2. A textured figure moving across a stationary textured background ("texture bar" stimulus) often elicited vigorous neural responses, but, on average, the responses to texture bars were significantly smaller than to solid (uniform luminance) bars. 3. Many cells showed direction selectivity that was similar for both texture bars and solid bars. However, on average, the direction selectivity measured when texture bars were used was significantly smaller than that for solid bars, and many cells lost significant direction selectivity altogether. The reduction in direction selectivity for texture bars generally reflected a combination of decreased responsiveness in the preferred direction and increased responsiveness in the null (opposite to preferred) direction. 4. Responses to a texture bar in the absence of a texture background ("texture bar alone") were very similar to the responses to solid bars both in the magnitude of response and in the degree of direction selectivity. Conversely, adding a static texture surround to a moving solid bar reduced direction selectivity on average without a reduction in response magnitude. These results indicate that the static surround is largely responsible for the differences in direction selectivity for texture bars versus solid bars. 5. In the majority of MT cells studied, responses to a moving texture bar were largely independent of whether the elements in the bar were of the same orientation as the background elements or of the orthogonal orientation. Thus, for the class of stimuli we used, orientation contrast does not markedly affect the responses of MT neurons to moving texture patterns. 6. The optimum figure length and the shapes of the length tuning curves determined with the use of solid bars and texture bars differed significantly in most of the cells examined. Thus neurons in MT are not simply selective for a particular figure shape independent of whatever cues are used to delineate the figure.

Changes in the response states of primate spinothalamic tract cells caused by mechanical damage of the skin or activation of descending controls.

1. The responses of a population of 318 spinothalamic tract (STT) cells to mechanical stimulation of the skin were recorded in anesthetized macaque monkeys by several teams of investigators. The responses were subjected to k-means cluster analysis, a multivariate statistical procedure. 2. For an analysis that pertained to the responsiveness of the neurons, the mean responses to four standard mechanical stimuli (Brush, Pressure, Pinch, and Squeeze) were used. Although no true clusters were found, the cells could be partitioned into four groups (called clusters a, b, c, and d) that responded progressively more vigorously to the stimuli. 3. For an analysis that pertained to the selectivity of the cells for various stimulus intensities, from innocuous to highly noxious, the data were normalized by taking the ratio of the mean response evoked by each stimulus to the sum of the responses and multiplying by 100. This procedure does not have a bias toward selection of any particular number of clusters and resulted in three clusters of STT cells. 4. Cluster 1 STT cells responded best to Brush. Cluster 2 cells responded weakly to Brush and Pressure and maximally to Pinch. Cluster 3 cells responded weakly to Brush, Pressure, and Pinch and maximally to Squeeze. 5. The response states of STT cells with respect to mechanical stimulation of the skin can be defined by their cluster assignments on the basis of the responsiveness (clusters a-d) and selectivity (clusters 1-3) of the cells. The response states of newly recorded STT cells can be determined by discriminant analysis from the nearest centroids of the two types of clusters in the reference population of STT cells. 6. No consistent changes in response state were detected when a second series of mechanical stimuli was applied 1 cm from the site stimulated initially or when the stimulus series was alternately repeated at the initial site and at progressively more proximal sites. However, when the stimulus series was applied five times to the initial site, the response state of five of eight cells tested showed a change. Although a change in response state required repetitive damage, even a single stimulus series increased background activity and responses to Brush at undamaged sites. 7. The background activity and responses to Brush and Pressure of all five STT cells recorded in the superficial laminae increased after repeated testing. The background activity of five STT cells recorded in the nucleus proprius also increased, but the responses of only three of the cells to Brush and Pressure increased.(ABSTRACT TRUNCATED AT 400 WORDS)

Two forms of inhibition of spinothalamic tract neurons produced by stimulation of the periaqueductal gray and the cerebral cortex

1. Recordings were made from the lumbosacral spinal cord in anesthetized macaque monkeys. The inhibitory effects of electrical stimulation of the periaqueductal gray (PAG) and the cerebral cortex or cerebral peduncle (CP) were tested and compared by recording 1) cord dorsum potentials evoked by stimulation of the sural nerve, 2) discharges recorded extracellularly, and 3) membrane potentials recorded intracellularly from spinothalamic tract (STT) neurons at rest (background activity) or in response to stimulation of the sural nerve. 2. Stimulation of the cortex or in the CP preferentially reduced the amplitude of the N1 and N2 waves of the cord dorsum potential evoked by stimulation of the sural nerve, without affecting the N3 wave. Stimulation of the PAG, on the other hand, reduced the amplitude of the N3 wave with little effect on the N1 and N2 waves. 3. The activity of 62 STT neurons was recorded extracellularly. Stimulation of the PAG or the cortex/CP inhibited nonpreferentially the responses of the neurons in the superficial laminae to all afferent inputs. On the other hand, stimulation of the PAG or the cortex/CP inhibited preferentially the responses of most STT neurons in deep layers of the dorsal horn to the small or large afferent input, respectively. 4. Thirty-five neurons were recorded intracellularly. The membrane potential of the neurons averaged -45.5 +/- 10.1 (SD) mV. All neurons were recorded in laminae III-VI; the neurons were of the wide-dynamic-range (WDR) type and had background activity. 5. The inhibitory effects of stimulation of the PAG were tested on all 35 neurons. In 32 of the neurons, stimulation of the PAG evoked a hyperpolarization. The background activity of the neurons was reduced (generally it completely ceased) by the hyperpolarization. In three neurons stimulation of the PAG did not evoke a hyperpolarization and the background activity of the neurons did not change. Nevertheless, the responses of these three neurons to afferent input were inhibited by stimulation in the PAG. 6. The inhibitory effects of stimulating the cortex and/or the CP were tested in 26 of the 35 neurons. Stimulation of the cortex and/or the CP evoked a hyperpolarization in all the neurons, although, in 10 of the 26 neurons, stimulation of the CP also evoked a depolarization. The hyperpolarization generally blocked the background activity of the neurons. 7. The effective stimuli in the PAG and the cortex/CP to evoke a hyperpolarization in STT neurons were short, high-frequency trains of pulses.(ABSTRACT TRUNCATED AT 400 WORDS)

Intracellular study of electrophysiological features of primate spinothalamic tract neurons and their responses to afferent inputs

1. Intracellular recordings were made from 43 spinothalamic (STT) neurons in the lumbosacral region of the spinal cord in anesthetized macaque monkeys. The antidromic responses of these neurons to electrical stimulation of the ventral posterior lateral (VPL) nucleus of the thalamus were examined, and orthodromic responses to electrical stimulation of the sural nerve or to mechanical stimulation of hindlimb skin were recorded to study the electrophysiological features of these neurons and their responses to afferent inputs. 2. The resting membrane potential of the neurons ranged from -26 to -70 mV and the antidromic latency from 2.3 to 9.1 ms. Three of the neurons were located in lamina 1 and were recorded so briefly that only antidromic and spontaneous activity could be studied. The rest of the neurons were located in laminae III-V and were of the wide-dynamic-range (WDR) type. 3. The antidromic action potentials recorded in the somas of STT neurons typically showed a fast rising phase and a short initial segment-somadendritic (IS-SD) delay. After repetitive antidromic stimulation, a progressive elongation of the IS-SD delay, widening of the spike, and failure of the SD spike were observed. 4. The afterpotential of the antidromic action potential consisted of a fast afterhyperpolarization (AHPf) and sometimes a delayed depolarization (DD) and a slow afterhyperpolarization (AHPs). The amplitude and the duration of the AHPs were progressively increased when longer trains of stimuli were used. When the membrane potential was hyperpolarized, the amplitude of the AHPs decreased, suggesting an involvement of K+ and/or Cl- ions. However, the AHPs completely disappeared when the strength of stimulation was adjusted to a level just below the threshold for the axon, suggesting that it was unlikely that recurrent inhibition contributed to the AHPs. 5. The background activity of 32 STT neurons was analyzed. The membrane potential at which spikes were triggered in these neurons was around -42 mV. The width and the rise time of the spontaneous spikes were shorter than those of antidromic action potentials, although the maximum rate of rise was similar. The heights of the spontaneous spikes were slightly shorter than those of antidromic action potentials. 6. Three types of background activity have been observed. One type had a very low average spontaneous rate with a bursting firing pattern, consisting of a few spikes superimposed on a depolarization. This type of activity was seen mostly in lamina I neurons. The second type of activity had a moderate to high spontaneous rate with a fairly constant interval between spikes.(ABSTRACT TRUNCATED AT 400 WORDS)

Tactile detection of slip: surface microgeometry and peripheral neural codes

1. The role of the microgeometry of planar surfaces in the detection of sliding of the surfaces on human and monkey fingerpads was investigated. By the use of a servo-controlled tactile stimulator to press and stroke glass plates on passive fingerpads of human subjects, the ability of humans to discriminate the direction of skin stretch caused by friction and to detect the sliding motion (slip) of the plates with or without micrometer-sized surface features was determined. To identify the associated peripheral neural codes, evoked responses to the same stimuli were recorded from single, low-threshold mechanoreceptive afferent fibers innervating the fingerpads of anesthetized macaque monkeys. 2. Humans could not detect the slip of a smooth glass plate on the fingerpad. However, the direction of skin stretch was perceived based on the information conveyed by the slowly adapting afferents that respond differentially to the stretch directions. Whereas the direction of skin stretch signaled the direction of impending slip, the perception of relative motion between the plate and the finger required the existence of detectable surface features. 3. Barely detectable micrometer-sized protrusions on smooth surfaces led to the detection of slip of these surfaces, because of the exclusive activation of rapidly adapting fibers of either the Meissner (RA) or the Pacinian (PC) type to specific geometries of the microfeatures. The motion of a smooth plate with a very small single raised dot (4 microns high, 550 microns diam) caused the sequential activation of neighboring RAs along the dot path, thus providing a reliable spatiotemporal code. The stroking of the plate with a fine homogeneous texture composed of a matrix of dots (1 microns high, 50 microns diam, and spaced at 100 microns center-to-center) induced vibrations in the fingerpad that activated only the PCs and resulted in an intensive code. 4. The results show that surprisingly small features on smooth surfaces are detected by humans and lead to the detection of slip of these surfaces, with the geometry of the microfeatures governing the associated neural codes. When the surface features are of sizes greater than the response thresholds of all the receptors, redundant spatiotemporal and intensive information is available for the detection of slip.

Colloidal volume expansion during acute cerebral ischaemia: assessed by local cerebral blood flow and computerized power ratio index

Colloidal volume expansion during acute cerebral ischaemia was assessed by local cerebral blood flow (CBF) and the power ratio index (PRI) in 8 anaesthetized Macaque monkeys. Focal cerebral ischaemia was produced by right middle cerebral artery occlusion. The animals were then volume expanded (to maximum cardiac output) with 6% hetastarch and then exsanguinated to baseline cardiac output. During volume expansion, local CBF in the ischaemic hemisphere increased from 25 +/- 12 to 39 +/- 23 cc/100 g/min (p less than 0.01) and during exsanguination decreased to 32 +/- 18 cc/100 g/min. Local CBF did not change significantly in the nonischaemic hemisphere. EEG power data, as assessed by PRI [(delta + theta power/alpha + beta power) x 100] changed significantly during blood volume manipulation. The mean PRI value in the right hemisphere deteriorated by increasing from 65 +/- 22 to 94 +/- 25 (p less than 0.01) following vessel occlusion but improved by decreasing to 81 +/- 23 (p less than 0.05) following volume expansion. Following exsanguination, the PRI value increased to 87 +/- 21. These data demonstrate the benefits of volume expansion during acute cerebral ischaemia. Changes in local CBF were consistently associated with changes in the PRI maps and values.

The primate spinocervicothalamic pathway: responses of cells of the lateral cervical nucleus and spinocervical tract to innocuous and noxious stimuli.

1. The response properties of neurons of the spinocervicothalamic pathway were studied in anesthetized macaque monkeys. Graded innocuous and noxious mechanical stimuli, including sinusoidal vibration and thermal pulses, were applied to the cutaneous receptive fields. 2. Forty-nine cells in the lateral cervical nucleus (LCN) were identified by antidromic activation from the ventral posterior lateral (VPL) nucleus of the contralateral thalamus. Twelve spinocervical tract (SCT) cells in the lumbosacral enlargement of the spinal cord were identified by antidromic activation from stimulation of the ipsilateral dorsolateral funiculus below C3 but not above C1. 3. Latencies for antidromic activation of LCN neurons averaged 2.3 ms, corresponding to a mean conduction velocity of approximately 17 m/s. Mean latency for orthodromic activation of LCN neurons following electrical stimulation of peripheral nerves was 12.6 ms. Overall mean conduction velocity for the monkey spinocervicothalamic pathway was estimated to be 29 m/s. 4. Most LCN cells had receptive fields on hairy skin, but some had input from glabrous skin and a few had subcutaneous fields. The receptive fields of most SCT cells had a glabrous skin component. Receptive fields tended to be smaller for SCT than LCN cells even for fields on a comparable part of the distal hindlimb. 5. Based on their responses to a series of mechanical stimuli (brushing, pressure, pinch, and squeeze), LCN and SCT cells were classified as low-threshold (LT), wide dynamic range (WDR), or high-threshold (HT) neurons. Most of the cells were in the LT or WDR classes. Thus the spinocervicothalamic pathway in the monkey differs from the spinothalamic tract (STT), in that STT cells are generally of the WDR or HT classes. 6. With the use of discriminant analysis, LCN and SCT neurons were allocated to categories determined from a k-means cluster analysis of the responses of 318 STT cells. The LCN and SCT neurons were in different proportions in the various categories than were STT cells, suggesting differences in the signaling properties of the spinocervicothalamic and spinothalamic paths. 7. Innocuous steady indentation of the skin failed to excite any of the neurons tested. Thus no positive evidence was obtained for an input to LCN neurons from slowly adapting mechanoreceptors. 8. Sinusoidal vibratory stimuli were used to test the ability of LCN and SCT neurons to follow repeated innocuous mechanical stimuli. Vibration at 10 Hz and an amplitude of 100 micron resulted in repetitive discharges in most LCN neurons and half the SCT neurons tested; many LCN neurons had thresholds below 25 micron.(ABSTRACT TRUNCATED AT 400 WORDS)

Primate nucleus gracilis neurons: responses to innocuous and noxious stimuli.

1. Recordings were made from 67 neurons in the nucleus gracilis (NG) of anesthetized macaque monkeys. All of the cells were activated antidromically from the ventral posterior lateral (VPL) nucleus of the contralateral thalamus. Stimuli used to activate the cells orthodromically were graded innocuous and noxious mechanical stimuli, including sinusoidal vibration and thermal pulses. 2. The latencies of antidromic action potentials following stimulation in the VPL nucleus were significantly shorter for cells in the caudal compared with the rostral NG. The mean minimum afferent conduction velocity of the afferent conduction velocity of the afferent fibers exciting the NG cells was 52 m/s, as judged from the latencies of the cells to orthodromic volleys evoked by electrical stimulation of peripheral nerves. The overall conduction velocity of the pathway from peripheral nerve to thalamus was approximately 40 m/s. 3. Cutaneous receptive fields on the distal hindlimb usually occupied an area equivalent to much less than a single digit. However, a few cells had receptive fields up to or exceeding the area of the foot. 4. NG cells were classified by their responses to graded mechanical stimulation of the skin as low threshold (LT) or wide dynamic range (WDR). No high-threshold NG cells were found. A special subcategory of pressure-sensitive LT (SA) neurons was recognized. Many of these cells were maximally responsive to maintained indentation of the skin. The sample of NG cells differed from the population of primate spinothalamic and spinocervicothalamic pathways so far examined, in having a larger proportion of LT neurons and a smaller proportion of WDR cells. A few NG cells responded best to manipulation of subcutaneous tissue. 5. Discriminant analysis permitted the NG cells to be assigned to classes determined by a k-means cluster analysis of the responses of a reference set of 318 primate spinothalamic tract (STT) cells. There were four classes of cells based on normalized responses of individual neurons and another four classes based upon responses compared across the population of cells. The NG cells were allocated to the various categories in different proportions than either primate STT cells or spinocervicothalamic neurons, consistent with the view that the functional roles of these somatosensory pathways differ. 6. Some of the pressure-sensitive NG cells were excited when the skin was stretched, suggesting an input from type II slowly adapting (Ruffini) mechanoreceptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Consistent features of the representation of the hand in area 3b of macaque monkeys.

Multiunit microelectrode recordings were used to explore the responsiveness and somatotopic organization of the representation of the hand in area 3b of anesthetized macaque monkeys. Major findings were as follows: Recording sites throughout the hand representation were activated by low-threshold cutaneous stimulation. Simple, punctate mechanical stimuli were highly effective in activating neurons. Neurons had small, restricted receptive fields. Representations of nearly all skin surfaces of the hand were demonstrated in individual monkeys. The basic topographic pattern found in all monkeys included the following: a large sequential representation of the glabrous digits from thumb to little finger from lateral to medial in cortex, and from proximal to distal hand parts in cortex extending down the caudal bank of the central sulcus; moderately large representations of radial and ulnar pads of the palm in respective lateral and medial cortical locations in the hand representation; and a relatively small, fragmented representation of the dorsal hand and dorsal digits, with the fragments interspersed within the representation of the glabrous hand. The proportions of the proximal, middle, and distal glabrous digits varied, so that the representation of the distal phalanx sometimes approached the dorsal border of area 3b with area 1. A comparison of the present findings with previous results from macaque monkeys indicates that the above-described features have been revealed under a variety of recording and anesthetic conditions. Consistencies in previous and present results strongly support the conclusions that the hand representation in area 3b of macaque monkeys is activated by cutaneous receptors throughout; is composed of neurons with relatively simple, small, cutaneous receptive fields; includes all skin surfaces of the hand; and is somatotopic for the glabrous skin with small, discontinuous, intercalated representations of fragments of the dorsal skin.

Velocity sensitivity and direction selectivity of neurons in areas V1 and V2 of the monkey: influence of eccentricity.

One hundred and forty two neurons in V1 and V2 were quantitatively tested using a multihistogram technique in paralyzed and anesthetized macaque monkeys. V1 neurons with receptive fields within 2 degrees from the fixation point (central V1 sample) and V1 neurons with eccentric receptive fields (15-25 degrees eccentricity, peripheral V1 sample) were compared to assess changes in velocity sensitivity and direction selectivity with eccentricity. The central V1 sample was compared with V2 neurons with receptive fields in the same part of the visual field (central V2 sample) to compare the involvement of both areas in the analysis of motion. Velocity sensitivity of V1 neurons shifts to faster velocities with increasing eccentricity. V1 and V2 neurons subserving central vision have similar preference for slow movements. All neurons could be classified into three categories according to their velocity-response curves: velocity low pass, velocity broad band, and velocity tuned. Most cells in parts of V1 and V2 subserving central vision are velocity low pass. As eccentricity increases in V1, velocity low-pass cells give way to velocity broad-band cells. There is a significant correlation between velocity upper cutoff and receptive field width among V1 neurons. The change in upper cutoff velocity with eccentricity depends both on temporal and spatial factors. Direction selectivity depends on stimulus velocity in most V1 cells. Neurons in the central V1 sample retain their direction selectivity at lower speeds than do neurons in the peripheral V1 sample. The proportion of direction-selective cells is low in both V1 and V2. In V1, direction selectivity decreases with eccentricity. In V1, both velocity upper cutoff and direction selectivity correlate more with laminar position than with receptive field type. The similarity between V1 of the monkey and area 17 of the cat, and the dissimilarity between V2 of the monkey and area 18 of the cat, are discussed.

Two distinct projection areas from tongue nerves in the frontal operculum of macaque monkeys as revealed with evoked potential mapping

Projection areas in the cerebral cortex from tongue nerves were investigated in anesthetized macaque monkeys ( Macaca fuscata). Three tongue nerves (lingual nerve, chorda tympani, and a lingual branch of the glossopharyngeal nerve) were electrically stimulated and thereby evoked mass field potentials were recorded with microelectrodes roving through the exposed and buried frontal operculum. Two distinct tongue nerve projection areas were thus located; one in the lower part of the precentral gyrus ventral to the inferior precentral sulcus, and the other in the medial part of the buried frontal operculum. The former corresponds to the “cortical masticatory area”, previously defined in macaque monkeys as involved in somatic sensation as well as mastication. However, the prominent projection from the chorda tympani and glossopharyngeal nerve branch, containing taste fibers, to this area suggests its involvement in taste sensation. The latter corresponds to the “pure gustatory area” defined in squirrel monkeys in both location and cytoarchitecture. However, projection to this area from the lingual nerve, which contains only somatic nerve fibers, suggests its involvement in somatic sensation, as well.

Responses of primate SI cortical neurons to noxious stimuli.

Recordings were made from single SI cortical neurons in the anesthetized macaque monkey. Each isolated cortical neuron was tested for responses to a standard series of mechanical stimuli. The stimuli included brushing the skin, pressure, and pinch. The majority of cortical neurons responded with the greatest discharge frequency to brushing the receptive field, but neurons were found in areas 3b and 1 that responded maximally to pinching the receptive field. A total of 68 cortical nociceptive neurons were examined in 10 animals. Cortical neurons that responded maximally to pinching the skin were also tested for responses to graded noxious heat pulses (from 35 to 43, 45, 47, and 50 degrees C). If the neuron failed to respond or only responded to 50 degrees C, the receptive field was also heated to temperatures of 53 and 55 degrees C. Fifty-six of the total population of nociceptive neurons were tested for responses to the complete series of noxious heat pulses: 46 (80%) exhibited a progressive increase in the discharge frequency as a function of stimulus intensity, and the spontaneous activity of two (4%) was inhibited. One population of cortical nociceptive neurons possessed restricted, contralateral receptive fields. These cells encoded the intensity of noxious mechanical and thermal stimulation. Sensitization of primary afferent nociceptors was reflected in the responses of SI cortical nociceptive neurons when the ascending series of noxious thermal stimulation was repeated. The population of cortical nociceptive neurons with restricted receptive fields exhibited no adaptation in the response during noxious heat pulses of 47 and 50 degrees C. At higher temperatures the response often continued to increase during the stimulus. The other population of cortical nociceptive neurons was found to have restricted, low-threshold receptive fields on the contralateral hindlimb and, in addition, could be activated only by intense pinching or noxious thermal stimuli delivered on any portion of the body. The stimulus-response functions obtained from noxious thermal stimulation of the contralateral hindlimb were not different from cortical nociceptive neurons with small receptive fields. However, nociceptive neurons with large receptive fields exhibited a consistent adaptation during a noxious heat pulse of 47 and 50 degrees C. Based on the response characteristics of these two populations of cortical nociceptive neurons, we conclude that neurons with small receptive fields possess the ability to provide information about the localization, the intensity, and the temporal attributes of a noxious stimulus.4+.

Responses of neurons in primate ventral posterior lateral nucleus to noxious stimuli.

1. Recordings were made from the caudal part of the ventral posterior lateral (VPLc) nucleus of the thalamus in anesthetized macaque monkeys. In additon to many neurons that responded only to weak mechanical stimuli, scattered neurons were found that responded to both innocuous and noxious stimulation or just to noxious stimulation of the skin. A total of 73 such neurons were examined in 26 animals. 2. Noxious stimuli included strong mechanical stimuli (pressure, pinch, and squeezing with forceps) and graded noxious heat (from 35 degrees C adapting temperature to 43, 45, 47, and 50 degrees C). The responses of the VPLc neurons increased progressively with greater intensities of noxious stimulation. The stimulus-response function when noxious heat stimuli were used was a power function with an exponent greater than one. 3. Repetition of the noxious heat stimuli revealed sensitization of the responses of the thalamic neurons to such stimuli. The threshold for a response to noxious heat was lowered, and the responses to supra-threshold noxious heat stimuli were enhanced. 4. The responses of VPLc neurons to noxious heat stimuli adapted after reaching a peak discharge frequency. The rate of adaptation was slower for a stimulus of 50 degrees C than for one of 47 degrees C. 5. For the six neurons tested, responses to noxious heat were dependent on pathways ascending in the ventral part of the lateral funiculus contralateral to the receptive field (ipsilateral to the thalamic neuron). In two cases, the input to the thalamic neurons from axons of the dorsal column was also conveyed by way of a crossed pathway in the opposite ventral quadrant. In another case, access to the thalamic neuron by way of ascending dorsal column fibers was demonstrated. 6. The thalamic neurons had restricted contralateral receptive fields that were somatotopically organized. Neurons with receptive fields on the hindlimb were in the lateral part of the VPLc nucleus, whereas neurons with receptive fields on the forelimb were in medial VPLc. 7. Ninety percent of the VPLc neurons tested that responded to noxious stimuli could be activated antidromically by stimulation of the surface of SI sensory cortex. It was possible to confirm that many of these cells project to the SI sensory cortex by using microstimulation. Successful microstimulation points were either within the SI cortex or in the white matter just beneath the cortex. 8. We conclude that some neurons in the VPLc nucleus are capable of signaling noiceptive stimuli. The nociceptive information appears to reach these cells through the ventral part of the lateral funiculus on the side contralateral to the receptive field, presumably by way of the spinothalamic tract. The VPLc cells are somatotopically organized, and they are thalamocortical neurons that project to the VPLc nucleus and SI cortex play a role in nociception.