Corticofugal influences on thalamic neurons during nociceptive transmission in awake rats

Pain is a multidimensional phenomenon and processed in a neural network. The supraspinal, brain mechanisms are increasingly recognized in playing a major role in the representation and modulation of pain. The aim of the current study is to investigate the functional interactions between cortex and thalamus during nociceptive processing, by observing the pain-related information flow and neuronal correlations within thalamo-cortical pathways. Pain-evoked, single-neuron activity was recorded in awake Sprague-Dawley rats with a Magnet system. Eight-wire microarrays were implanted into four different brain regions, i.e., the primary somatosensory (SI) and anterior cingulate cortex (ACC), as well as ventral posterior (VP) and medial dorsal thalamus (MD). Noxious radiant heat was delivered to the rat hind paws on the side contralateral to the recording regions. A large number of responsive neurons were recorded in the four brain areas. Directed coherence analysis revealed that the amount of information flow was significantly increased from SI cortex to VP thalamus following noxious stimuli, suggesting that SI cortex has descending influence on thalamic neurons during pain processing. Moreover, more correlated neuronal activities indicated by crosscorrelation histograms were found between cortical and thalamic neurons, with cortical neurons firing ahead of thalamic units. On basis of the above findings, we propose that nociceptive responses are modulated by corticothalamic feedback during nociceptive transmission, which may be tight in the lateral pathway, while loose in the medial pathway.     

Responsiveness of ventrobasal thalamic neurons after suppression of S1 cortex in the anesthetized rat

Corticofugal influences on the responses of ventrobasal (VB) thalamic neurons to repetitive stimuli were studied in anesthetized rats by suppressing primary somatosensory (S1) electrocortical activity with topically applied lidocaine. Effective concentrations of lidocaine were confined to S1 and immediately adjacent cortex and suppressed evoked S1 responses and corticofugal discharges. Suppression of S1 cortex reduced the average number of spikes discharged by 83 VB neurons in response to each of 25 electrical somatic stimuli delivered at frequencies ranging from 1 to 50 Hz. Of 20 units studied both before and after S1 suppression, 14 (70%) showed a similar reduced response to repetitive stimuli. Cortical suppression produced no consistent changes in spontaneous activity, somatic stimulus threshold, response latency, or size of receptive field. There was no significant difference in the effect of cortical suppression on the responsiveness of 8 VB neurons to repetitive medial lemniscal, as compared to somatic, stimuli. We conclude that, in the anesthetized rat, S1 corticofugal activity facilitates somato-sensory transmission to VB neurons and that this facilitation is mediated, at least in part, by corticothalamic neurons.     

Heterogeneous axonal arborizations of rat thalamic reticular neurons in the ventrobasal nucleus

The γ-aminobutyric acid (GABA)-containing neurons of the thalamic reticular nucleus (nRt) are a major source of inhibitory innervation in dorsal thalamic nuclei. Individual nRt neurons were intracellularly recorded and labelled in an in vitro rat thalamic slice preparation to investigate their projection into ventrobasal thalamic nuclei (VB). Camera lucida reconstructions of 37 neurons indicated that nRt innervation ranges from a compact, focal projection to a widespread, diffuse projection encompassing large areas of VB. The main axons of 65% of the cells gave rise to intra-nRt collaterals prior to leaving the nucleus and, once within VB, ramified into one of three branching patterns cluster, intermediate, and diffuse. The cluster arborization encompassed a focal region averaging approximately 25,000 μm² and contained a high density of axonal swellings, indicative of a topographic projection. The intermediate structure extended across an area approximately fourfold greater and also contained numerous axonal swellings. The diffuse arborization of nRt neurons covered a large region of VB and contained a relatively low density of axonal swellings. Analysis of somatic size and shape revealed that diffuse arborizations arose from significantly smaller, fusiform-shaped somata. Cytochrome oxidase reactivity or parvalbumin immunoreactivity was used to delineate a discontinuous staining pattern representing thalamic barreloids. The size of a cluster arborization closely approximated that of an individual barreloid. The heterogeneous arborizations from nRt neurons may reflect a dynamic range of inhibitory influences of nRt on dorsal thalamic activity. © 1996 Wiley-Liss, Inc.     

Axon collaterals in the thalamic reticular nucleus from thalamocortical neurons of the rat ventrobasal thalamus

Thalamocortical relay neurons from the rat ventrobasal nucleus were identified physiologically and injected intracellularly with horseradish peroxidase. The axons of these cells were followed through serial sections in order to determine if collaterals were given off within the ventrobasal nucleus or the thalamic reticular nucleus. No local collaterals were seen in the ventrobasal nucleus, thus indicating that interactions between relay cells in this nucleus are minimal. Of axons that could be followed into the internal capsule, 76% gave off visible collaterals in the thalamic reticular nucleus. Half of these axons had collaterals showing extensive branching with the potential of innervating a large number of thalamic reticular neurons. The other half had short, simple branches of restricted extent. No correlations were found between the physiological properties of a cell and the existence or extent of axon collaterals. These results describe the anatomical basis for the initial part of a feedback loop through the thalamic reticular nucleus that provides the major inhibitory influence on rat ventrobasal neurons.     

Encoding of noxious heat messages in neurons of the ventrobasal thalamic complex of the rat

Ventrobasal thalamic neurons responsive to noxious mechanical stimuli were tested with noxious heat stimuli graded in temperature, surface-area and duration. Experiments were performed by plunging the tail of intact, lightly anesthetized rats into a temperature-controlled water bath.Seventeen of 24 neurons encoded stimulus temperature by frequency of discharge although the responses of 6 of these 17 reached a plateau at the highest temperatures. Alternatively, the cell population might code stimulus temperature by a recruiting mechanism since response thresholds were distributed between 40 and 50°C.Some units also increased their discharge in parallel with an increase in stimulus area and/or duration. Analyses of discharge patterns were performed. A decrease of discharge frequency during stimulation was not observed before several tens of seconds had elapsed. Thus, the average response of the cell population to 15, 30 and 60 sec stimuli showed no clear ‘adaptation’.In our conditions, i.e. with most of the stimulations limited to a duration of 15 sec each, sensitization to heat was observed after 55 and 60°C, but not after 50°C.These data indicate that noxious heat stimulus parameters are coded at the thalamic level in the rat by both an increase in discharge and a progressive recruitment of units.     

Modifications in the responsiveness of rat ventrobasal thalamic neurons at different stages of carrageenin-produced inflammation

The present study was aimed at analyzing the responsiveness of the ventrobasal (VB) thalamic neurons in rats presenting with a hyperalgic carrageenin-produced inflammation. The following were studied: the responses of the same VB neuron, before and 15-145 min after the plantar injection of carrageenin in a part of its receptive field (RF) (acute phase); the responses of VB neurons located in the thalamus contralateral to the hyperalgesic inflamed paw, 24-96 h after the injection (subacute phase); and the effect of a local anesthetic injected in the inflamed paw, and that of an intravenous injection of Aspirin, on neuronal response modifications. Responses of VB neurons initially activated by light tactile stimuli (group 1; n = 4) and by moderate joint stimulation (group 3; n = 4) were not modified in the early period following the carrageenin injection. By contrast, in the first few minutes following the injection. VB neurons exclusively driven by noxious mechanical and thermal stimuli (group 2; n = 23), exhibited a clear enhancement of their responses, which persisted during the observation period. These modifications were also observed for responses obtained from part of the RF remote from the injection site; moreover there was an extension of the RF to areas distant from the injured paw. The local injection of an anesthetic (Xylocaine) in this paw, suppressed the modifications of responses of group 2 neurons, elicited not only from the injected paw, but also from the remote parts of the RF. At this time Aspirin was almost inefficient (even at the dose of 100 mg/kg) on responses of these group 2 neurons. In the subacute phase responses of 72 somatosensory neurons were analyzed. Twenty-five of 72 responded to rapid repetitive light tactile stimulation applied on a small contralateral RF (group 1); their responses were similar to those encountered in a normal situation. Thirty-three of 72 neurons responded to intense mechanical stimuli such as pinches (group 2). For half of them the response characteristics were similar to those described in the normal rat; for the other half responses appeared 'faded': short duration; absence of after-discharge; poor reproducibility. Fourteen of 72 neurons responded to moderate stimulation of the joints, deep tissues and/or surrounding cutaneous areas of the inflamed paw (group 3). Their RF was mostly unilateral, i.e. contralateral to the recording site; the responses were sustained during the stimulation but rarely exhibited after-discharge.(ABSTRACT TRUNCATED AT 400 WORDS)     

Corticofugal influences on the reticulospinal neurons of gigantocellular nucleus in cats]

Stimulation of the motor cortex evoked excitatory and inhibitory PSP in reticulospinal neurons of the cat gigantocellular nucleus. EPSP were recorded in 94.3% of the investigated neurons and IPSP in 5.7%. Analysis of the presynaptic pathways showed that 77.4% of EPSPs appeared through monosynaptic and 22.6% through polysynaptic corticoreticular connections. According to latency, duration and rise time all monosynaptic EPSP were divided into two groups (fast and slow). Obviously, fast EPSPs are generated by fast corticobulbar fibres and slow ones by slow fibres. IPSP were recorded in neurons which were also inhibited by stimulation of the ventral funiculi of the spinal cord. It is suggested that motor cortical signals can be transmitted to the spinal cord through both mono- and polysynaptic connections of the fast and slow pyramidal neurons with reticulospinal neurons.     

Inhibition of thalamic ventrobasal complex neurons by glutamate infusion into the thalamic reticular nucleus in rats

In urethane-anesthetized rats a 0.36-mm metallic cannula for infusion was positioned in the somatosensory component of the thalamic reticular nucleus (sTR), where movement of the vibrissae evoked neuronal discharge. Infusion there of 0.125-0.5 microliter of a 50 mM solution of glutamate over a 1-min period suppressed both spontaneous and evoked discharge of neurons in the ventrobasal complex (VB), but only for those which also responded to vibrissal stimulation. VB neurons activated by somatosensory stimuli at other locations were unaffected. Thus, excitation of neurons in sTR inhibits those in VB, but the effect appears to be highly coordinated somatotopically.     

Multiple-joint neurons in somatosensory cortex of awake monkeys

(1) The somatosensory cortex of alert monkeys, 55 neurons were found which receive convergent information from two or more adjacent joints. Most of these multiple-joint neurons were excited by postures of the hand, particularly those involved in grasping.

(2) Three basic types of joint interactions were observed. The simplest neurons (occlusion neurons) responded to postures of several different joints, but combination of the preferred postures produced no further increase in firing. The more complex cells showed summated responses to combined postures of adjacent joints, or subliminal facilitation between joints. The responses of both summation neurons and subliminal facilitation neurons were graded with joint angle, and there was an optimum or preferred position for both joints which gave the strongest response.

(3) Multiple-joint neurons may provide a neuronal substrate for extracting postural information from several different populations of kinesthetic neurons. They therefore act as feature-detecting neurons, abstracting information about specific body postures.

Corticofugal effects on the activity of thalamic taste cells

To examine corticofugal influences on afferent thalamic cell responses in the gustatory system, effects of cortical conditioning stimuli on the responses of thalamic taste cells to peripheral stimulation were examined in the rat. Two types of excitability change of thalamic cells were observed; one is inhibitory (for about 60 msec) (20%) and the other is inhibitory (for about 10 msec)-facilitatory (for about 60 msec) (40%) to conditioning stimulus applied to the ventral gustatory area, and half of the cells belonging to the latter type also showed a similar pattern with more marked and prolonged excitability changes to conditioning stimulus applied to the dorsal gustatory area. It was suggested that some of the response characteristics of thalamic and cortical taste cells were attributed to the corticofugal feedback loop.     

Contrasting properties of neurons in two parts of the primary motor cortex of the awake rat

Features of neuronal activity in two subdivisions of primary motor cortex (MI) were recorded in awake rats. Neurons in the caudal part of MI, which overlaps part of the somatic sensory cortex, discharge with brief bursts in conjunction with isometric bar pressing with the forelimb. Cells in this caudal region are activated by cutaneous stimuli. In the rostral part of MI, neurons discharge prior to and during forelimb force changes, begin to discharge earlier than in the caudal zone, and have non-cutaneous or unidentifiable receptive fields. These results suggest separate motor control functions for rostral and caudal parts of rat MI.     

Innervation of VIP-immunoreactive neurons by the ventroposteromedial thalamic nucleus in the barrel cortex of the rat

We investigated the synaptic terminals of fibers originating in the ventroposteromedial thalamic nucleus (VPM) and projecting to the main input layers (IV/III) of the rat posteromedial barrel subfield. It was our aim to determine whether or not the subpopulation of vasoactive intestinal polypeptide (VIP)-immunoreactive neurons in these layers are directly innervated by the sensory thalamus. Anterograde tracing with Phaseolus vulgaris leucoagglutinin (PHA-L) and immunohistochemistry for VIP were combined for correlated light and electron microscopic examination. Columns of cortical tissue were well defined by barrel-like patches of PHA-L-labeled fibers and boutons in layers IV and III. Within these columns VIP-immunoreactive perikarya were located mainly in supragranular layers. Marked perikarya were also seen in infragranular layers, but their immunoreactivity was often weaker. Granular layer IV, which is the main terminal field for thalamic fibers, contained fewer VIP neurons than supragranular layers. In the light microscope, however, PHA-L-labeled fibers appeared to contact the somata or proximal dendrites of 60–86% of the layer IV VIP neurons. By contrast, only 18–35% of the VIP neurons in the supragranular layers, which receive a moderately dense projection from the VPM, appeared to be contacted. PHA-L-labeled boutons were seen close to 13–25% of infragranular VIP-positive cells. Electron microscopy showed that thalamic fibers formed at most four asymmetric synapses on a single layer IV, VIP-positive neuron. Although the proportion of VIP-positive neurons with labeled synapses was lower in supragranular layers, most of them shared multiple asymmetric synapses with labeled thalamic fibers. Up to six labeled synapses were seen on individual VIP neurons in layer III. We conclude that subpopulations of VIP-immunoreactive neurons, located in layers IV, III, and II are directly innervated by the VPM. These neurons may be involved in the initial stages of cortical processing of sensory information from the large, mystacial vibrissae. Since VIP is known to be colocalized with the inhibitory transmitter GABA, it is likely that VIP neurons participate in the shaping of the receptive fields in the barrel cortex. © 1996 Wiley-Liss, Inc.     

Baroreceptive and somatosensory convergent thalamic neurons project to the posterior insular cortex in the rat

Connectivity between the rat posterior insula and the ventrobasal thalamus has been demonstrated anatomically. Neurons convergent for baroreceptor and nociceptive input have also been identified in the homologous anterior insula of the primate. Whether similar convergent cells exist in the ventrobasal thalamus was investigated in 30 urethane anesthetized male Sprague--Dawley rats. Six classes of cells were identified in the right ventrobasal thalamus: (a) 83/159 (52%) baroreceptive and nociceptive convergent units; (b) 2/159 (1%) convergent cells responding to baroreceptor activation and light touch; (c) 44/159 (28%) purely nociceptive units; (d)10/159 (6%) purely baroreceptive units; (e) 1/159 (0.6%) cells responding to brush alone and (f) 19/159 (12%) unresponsive units. Of the viscerosomatic convergent cells, 66/85 (78%) were situated in the ventroposterolateral nucleus (VPL), 6/85 (7%) in the ventroposterolateral parvicellular nucleus (VPLpc), and 13/85 (15%) in the ventroposteromedial nucleus (VPM). Fifteen right ventrobasal thalamic units were antidromically activated and 34 units orthodromically activated by right posterior insular microstimulation. Cobalt injection into the right ventrobasal thalamus blocked the right insular response to baroreceptor activation by >70%. These data indicate: (a) baroreceptive and somatosensory nociceptive convergent units exist in the ventrobasal thalamus; (b) thalamic convergent neurons project directly to the ipsilateral posterior insula and receive reciprocal insulothalamic projections; and (c) a significant proportion of baroreceptor input relays to the posterior insula through the ipsilateral ventrobasal thalamus.     

Effects of prenatal exposure to ethanol on systems matching: the number of neurons in the ventrobasal thalamic nucleus of the mature rat.

Following prenatal exposure to ethanol, rats have a 1/3 fewer neurons in the second order (principal sensory nucleus of the trigeminal nerve) and fourth order neurons (somatosensory cortex) of the trigeminal-somatosensory pathway than do controls. Based on the numerical matching hypothesis, we predict that the number of third-order neurons (in the ventrobasal nucleus of the thalamus; VB) also will show a similar effect of prenatal ethanol exposure. Stereological methods were used to determine the total number of neurons in the VB on postnatal day 30. Surprisingly, prenatal exposure to ethanol had no effect on the VB volume or on the number of VB neurons. Thus, prenatal exposure to ethanol induces numerical imbalances within the trigeminal-somatosensory system.     

Evidence for central phenomena participating in the changes of responses of ventrobasal thalamic neurons in arthritic rats

In this study performed in the Freund's adjuvant-induced arthritic rat, a local injection of lidocaine in one hind paw strongly depressed the ventrobasal thalamic neuronal responses to mild stimulation of both ankles. In parallel, a behavioral study provided evidence for a bilateral hypoalgesia, tested by the vocalization threshold to paw pressure, after a unilateral anesthetic block. The involvement of central phenomena in the changes of neuronal responsivity described in this model of experimental pain is therefore suggested.     

Tactile responses of hindpaw, forepaw and whisker neurons in the thalamic ventrobasal complex of anesthetized rats

The majority of studies investigating responses of thalamocortical neurons to tactile stimuli have focused on the whisker representation of the rat thalamus: the ventral–posterior–medial nucleus (VPM). To test whether the basic properties of thalamocortical responses to tactile stimuli could be extended to the entire ventrobasal complex, we recorded single neurons from the whisker, forepaw and hindpaw thalamic representations. We performed a systematic analysis of responses to stereotyped tactile stimuli − 500 ms pulses (i.e. ON–OFF stimuli) or 1 ms pulses (i.e. impulsive stimuli) − under two different anesthetics (pentobarbital or urethane). We obtained the following main results: (i) the tuning of cells to ON vs. OFF stimuli displayed a gradient across neurons, so that two-thirds of cells responded more to ON stimuli and one-third responded more to OFF stimuli; (ii) on average, response magnitudes did not differ between ON and OFF stimuli, whereas latencies of response to OFF stimuli were a few milliseconds longer; (iii) latencies of response to ON and OFF stimuli were highly correlated; (iv) responses to impulsive stimuli and ON stimuli showed a strong correlation, whereas the relationship between the responses to impulsive stimuli and OFF stimuli was subtler; (v) unlike ON responses, OFF responses did not decrease when stimuli were moved from the receptive field center to a close location in the excitatory surround. We obtained the same results for hindpaw, forepaw and whisker neurons. Our results support the view of a neurophysiologically homogeneous ventrobasal complex, in which OFF responses participate in the structure of the spatiotemporal receptive field of thalamocortical neurons for tactile stimuli.     

Corticofugal connections between the cerebral cortex and the vestibular nuclei in the rat

The distribution of cortical efferent connections to the vestibular nuclei was quantitatively analyzed by means of retrograde axonal transport of horseradish peroxidase, wheat germ agglutinin-horseradish peroxidase, and Fast Blue in rats. The tracer substances were injected into the spinal vestibular nucleus (SpVe), the caudal part of the medial vestibular nucleus (MVe), and nucleus X of Brown Norwegian rats. Projections to the vestibular nuclei were revealed bilaterally, but predominantly contralaterally from five cortical areas: (1) the parietotemporal region (PT) which occupied the caudal two-thirds of the secondary somatosensory area and spread over the caudal part of the primary somatosensory area and the visceral cortex; (2) the anterior forelimb (AF) overlapping the anterior part of the forelimb area and the transitional zone; (3) the anterior hindlimb (AH) overlapping the anterior part of the hindlimb area and the transitional zone; (4) the lateral forelimb (LF) centered in the intercalated zone lateral to the forelimb area; and (5) the ventrotemporal region (VT) located at the ventral part of the temporal cortex. In addition to these cortical fields, the frontal cortex was found to project directly to the vestibular nuclei. These corticofugal projections were verified in experiments in which biocytin was injected into the rat PT. Anterogradely labelled fibers were traced predominantly contralaterally to the SpVe, caudal part of the MVe, and nucleus X. It is suggested that the rat corticofugal projections to the caudal vestibular nuclei modify vestibular reflexes to assist in coordinating eye, head and body movements during locomotion.     

Properties of kinesthetic neurons in somatosensory cortex of awake monkeys

(1) To study neural mechanisms used to encode kinesthetic information in somatosensory cortex of awake monkeys, we recorded from 227 single neurons responsive to joint movement or specific postures of the forelimb or hand (kinesthetic neurons). Unit responses were characterized quantitatively with respect to: (a) firing patterns; (b) responses to ramp changes in joint position and joint velocity; and (c) responses to sinusoidal joint movements.

(2) Kinesthetic neurons were divided into 3 groups. Rapidly-adapting neurons (44%) responded only to joint movement, giving a burst of impulses proportional to velocity. They showed no tonic responses to limb posture. Two populations of tonically active neurons were observed: slowly-adapting neurons (43%) and postural neurons (13%). Both types increased their firing rates with increasing degrees of flexion or extension, showing maximum excitation at the extremes of joint position in the preferred direction. They were distinguished by their sensitivity to the velocity of movement, the size of the angle over which they respond, and the phase relation of their responses to sinusoidal joint movement.

(3) The firing rates of kinesthetic neurons in S-I cortex are functions of both joint angle and joint velocity. The importance of each component varies in the 3 classes: velocity of movement is the most important determinant of firing rates of rapidly-adapting and slowly-adapting kinesthetic neurons, and joint angle predominates the responses of postural neurons.