Electrically and mechanically evoked nociceptive neuronal responses in the rat anterior cingulate cortex.

The present study examined nociceptive properties of anterior cingulate cortical (ACC) neurons following application of peripheral noxious electrical and mechanical stimulations to anesthetized rats. Among a total of 108 recorded neurons, 59 units were excited or inhibited by noxious electrical or mechanical stimulation. Of these 59 cells, 38% were located in area 24b, another 38% were located in area 8, and the remaining cells were located in areas 24a and 25. The noxious stimulus-responsive neurons were located predominately in layers V (58%) and III (30%), and the remaining cells were located in layers II and VI. The latency of evoked unit activities was 209.75 +/- 26.62 ms and the threshold of the ACC responses was 10 times greater than that in primary somatosensory cortex (SI). Morphine treatment (5 mg/kg, i.v.) increased activity in evoked ACC neurons. This effect was reversed by naloxone (2 mg, i.v.). Nociceptive neurons in the ACC were distributed in area 24 and motor related regions. The locations and properties of evoked responses indicated that ACC neurons may play a role in avoidance behavior in the context of affective aspects of nociceptive information processing.

Current source density analysis of laser heat-evoked intra-cortical field potentials in the primary somatosensory cortex of rats.

The role of the primary somatosensory cortex in thermal pain perception has been established. However, the cortical circuitry that mediates the thermo-nociceptive information processing has not been elucidated. The aim of present study was to investigate the intracortical synaptic currents in primary somatosensory cortex evoked by short laser pulses and to determine their transmission pathway. Noxious CO2 laser pulse stimuli or innocuous electrical and mechanical stimuli were delivered to the hind paw of halothane-anesthetized rats. Multi-channel field potentials were recorded simultaneously in primary somatosensory cortex and laminar-specific transmembrane currents were analyzed using a current source density method. A distinct spatial-temporal pattern of intra-cortical sink source currents was evoked by laser pulse stimuli. The amplitude of the early component was graded by laser energy output and influenced by contralateral signals, whereas the late components were not intensity-dependent and exhibited bilateral excitation. Intra-cortical current flows revealed that synaptic activation occurred initially at layers IV and VI separately and then was relayed transynaptically to the more superficial and the deeper layers. Latency, amplitude and intracortical distributions of the activated intra-cortical currents evoked by noxious stimuli differed significantly from those evoked by innocuous stimuli. Conduction velocity data together with the results of tetrodotoxin, capsaicin and morphine treatments indicated that the early and late components were mediated separately by A-delta and C fibers. Our results suggest that large and small diameter thermal nociceptive afferents generated laminar-specific intracortical synaptic currents in primary somatosensory cortex and that these excitatory synaptic currents were conveyed separately by lateral and medial thalamic nuclei.

Differential patterns of extracellular signal-regulated kinase-1 and -2 phosphorylation in rat limbic brain regions after short-term and long-term inhibitory avoidance learning.

Activation of the extracellular signal-regulated kinase-1 and -2 has been shown to be required for neural plasticity and memory. Previous pharmacological studies have demonstrated that inhibition of extracellular signal-regulated kinase-1 and -2 blocks inhibitory avoidance retention. The aim of the present study was to investigate the different neural substrates underlying short- and long-term inhibitory avoidance learning and memory in rats using phosphorylated extracellular signal-regulated kinase-1 and -2 labeling as an index of plasticity. Short- and long-term retention tests were given 10 min or 24 h after inhibitory avoidance training. A significant elevation in the number of phosphorylated extracellular signal-regulated kinase-1 and -2-immunoreactive neurons was observed in area 1 of anterior cingulate cortex, the secondary motor cortex, lateral orbital cortex, claustrum, and the medial amygdala nucleus after the short-term inhibitory avoidance test. After the long-term retention test, phosphorylated extracellular signal-regulated kinase-1 and -2-immunoreactive neurons were localized in area 1 of anterior cingulate cortex, prelimbic cortex, and the central nucleus of amygdala. This suggests that phosphorylated extracellular signal-regulated kinase-1 and -2-immunoreactivity may reveal different brain regions involved in the storage of short- and long-term aversive memories.

A fMRI study of brain activations during non-noxious and noxious electrical stimulation of the sciatic nerve of rats.

An acute pain animal model for fMRI study would provide useful spatial and temporal information for studying the supraspinal nociceptive neuronal responses. The aim of the present study was to investigate whether the nociceptive responses in different brain areas can be differentiated by using functional magnetic resonance imaging (fMRI) in anesthetized rats. Functional changes in brain regions activated by noxious or non-noxious stimuli of the sciatic nerve were investigated using fMRI in a 4.7 T MR system in alpha-chloralose anaesthetized rats. To determine the electrical intensity for noxious and non-noxious stimuli, compound action potential recording was employed to reveal the type of fibers activated by graded electrical stimulation of sciatic nerve. It showed that innocuous A-beta fibers were excited by two times the muscle twitch threshold and nociceptive A-delta and C fibers were recruited and excited by 10 and 20 times threshold, respectively. A series of four-slice gradient echo images were acquired during innocuous (two times threshold) and noxious (10 and 20 times threshold) stimuli in a 4.7 T MR system. Contralateral somatosensory cortex was the most prominent brain area activated by innocuous stimuli. Both signal intensity and activated areas were significantly increased in the somatosensory cortex, cingulate cortex, medial thalamus and hypothalamus during noxious stimuli. These four brain areas activated by noxious stimuli were significantly suppressed by prior intravenous injection of morphine (5 mg/kg). The present findings demonstrated that the difference of the innocuous and nociceptive responses in the brain could be detected and localized by an in vivo spatial map using fMRI. Results suggest that fMRI may be an invaluable tool for studying pain in anesthetized animals.

Evoked responses of the anterior cingulate cortex to stimulation of the medial thalamus.

In the present study we characterized the field potentials in the anterior cingulate cortex (ACC) evoked by electrical stimulation of the medial thalamus (MT), and elucidated the synaptic organization of the ACC. Male Sprague Dawley rats were maintained in general anesthesia by alpha-chloralose (50 mg/kg, i.v.). Tungsten micro-electrodes were used for electric stimulation and recordings. The field potentials and multiple unit activities in the ACC were evoked by electric stimulation of the MT where the nociceptive responses were identified. A MT-evoked positive-negative potential was recorded on the medial frontal surface. The polarity of the surface negative potential was reversed between 0.5 to 1.0 mm in the deep layer of the ACC. Maximum evoked negative potential appeared at about 4 mm anterior to the bregma and 1 mm lateral to the midline. The maximum evoked positive potential occurred at about 3 mm anterior to the bregma and 1 mm lateral to the midline. The evoked multiple unit activities coincided with the deep negative field potential at a latency between 16 ms and 24 ms at a depth between 0.5 mm and 1.5 mm in the ACC. These electrophysiological findings confirmed that nociceptive information in the MT is transmitted to the ACC and trans-synaptically activates deeper and more superficial layers of cortical neurons.

Electrophysiological study of the connection between medial thalamus and anterior cingulate cortex in the rat.

We characterized the neuronal properties of the anterior cingulate cortex (ACC) evoked by electrical stimulation of the medial thalamus (MT). MT stimulation sites were found by their neuronal responses to noxious stimuli. Of 487 units identified histologically in the rat ACC, 94% were activated trans-synaptically at different areas of the ACC. Six percent of MT-evoked ACC units were activated antidromically and all of these units projected to a specific nucleus of MT. We suggest that MT nuclei mediate different aspects of nociceptive information to specific ACC areas, and that nociceptive information in the MT is modulated reciprocally by activities from the ACC.

The suppressive effect of electrical stimulation on nociceptive responses in the rat.

BACKGROUND AND PURPOSE: The aim of this investigation was to study the effect of electrical stimulation on nociceptive responses within the lumbar levels of the rat spinal cord. METHODS: A single high-energy thermal pulse produced by a surgical laser stimulator (5 W, 30 milliseconds) was applied on the plantar surface of the hind paws of male Sprague-Dawley rats. The spinal cord field potential evoked by the laser pulse was used as an indicator of thermosensitive nociceptive responses. Low-intensity single stimulation, high-intensity single stimulation, low-intensity train stimulation, and high-intensity train stimulation were applied on the common peroneal nerve with protected cuff electrodes in different trials. RESULTS: Neither low-intensity nor high-intensity single stimulation suppressed field potentials. In contrast, low-intensity train stimulation elicited partial inhibition of field potentials. Furthermore, high-intensity train stimulation elicited biphasic inhibition at a wider range of intervals lasting for 20 seconds. CONCLUSION AND DISCUSSION: The results demonstrate that two modes of train electrical stimulation can produce two patterns of fast-onset (within milliseconds), short-duration (within 20 seconds) inhibition of field potentials in the spinal cord. These results provide evidence that noxious heat-related impulses are modulated by the presence of specific electrical stimulation. The clinical application of transcutaneous electrical nerve stimulation to block pain is supported.

Intrathecally administered c-fos antisense oligodeoxynucleotide decreases formalin-induced nociceptive behavior in adult rats.

c-fos antisense strategy was applied as a pharmacological approach to characterize its dose-dependent role and reversibility in the reduction of formalin-induced hyperalgesia. Nociceptive behavioral responses (weighted score, flinching response, licking/biting) following formalin (50 microl 5%) injection were assessed in adult Wistar rats receiving different doses (50 nM, 250 nM) of intrathecally administered c-fos antisense oligodeoxynucleotides at different times prior to formalin injections. The treatments dose dependently decreased both Fos immunoreactivity expression in dorsal horn of rat lumbar spinal cord and all nociceptive measures in the tonic phase of the formalin test. c-Fos correlated well with weighted pain score and/or flinching responses, but not with licking/biting behavior. With the exception of a 48-120 h period required for licking/biting behavior to be restored to its normal status, the suppressive effect on c-fos expression and other nociceptive behaviors disappeared 48 h following c-fos antisense oligodeoxynucleotide treatment. The results suggest a pharmacological potential of c-fos antisense oligodeoxynucleotides in the central nervous system to block immediate-early genes and their resulting physiological consequence following noxious stimulus.

Protein synthesis inhibitor cycloheximide dose-dependently decreases formalin-induced c-Fos protein and behavioral hyperalgesia in rats.

We had previously demonstrated that c-fos antisense oligodeoxynucleotides dose-dependently suppressed formalin-induced c-Fos protein and behavioral hyperalgesia. To test whether de novo protein synthesis is required for the development of persistent pain after peripheral inflammation, we observed formalin-induced spinal c-Fos protein and nociceptive behaviors following pretreatment with cycloheximide, a protein synthesis inhibitor. Cycloheximide dose-dependently inhibited formalin-induced spinal c-Fos protein and tonic nociceptive responses. The possible non-specific effects other than protein synthesis inhibition on nociceptive behavior were carefully discussed and excluded. These results provide further support to the hypothesis that de novo protein synthesis is essential for the development of behavioral hyperalgesia.

Nitrous oxide or halothane, or both, fail to suppress c-fos expression in rat spinal cord dorsal horn neurones after subcutaneous formalin.

In rats injected s.c. with formalin, behavioural correlates of the amount and pattern of Fos-like immunoreactivity (Fos-Ll) (molecular responses to pain) were studied to test if early phase treatment with 75% nitrous oxide or 2% halothane, or both, suppressed subsequent spinal sensitization. Rats were allocated to four treatment groups: (1) 100% oxygen (control, n = 15), (2) 75% nitrous oxide (0.5 MAC, n = 12), (3) 2% halothane (1 MAC, n = 12), and (4) 75% nitrous oxide with 2% halothane (1.5 MAC, n = 18) for 20 min. Each rat then received a s.c. injection of 1% formalin 50 microliters into the left hindpaw and anaesthesia was maintained for another 5 min (early phase). A fifth group of rats receiving fentanyl 100 micrograms kg-1 (n = 12) 10 min before formalin injection were studied simultaneously as a positive control. Rats in all groups were killed 60 min after formalin injection and maximal counts of Fos-Ll labelled neurones in the dorsal horn of the rat spinal cord were compared according to laminar distribution. Formalin-induced behavioural hyperalgesia during the early phase was suppressed completely by fentanyl, 75% nitrous oxide, or 2% halothane, or both. The late phase response was attenuated by all four anaesthetic regimens within 20 min after injection, whereas behavioural scores for the nitrous oxide, halothane, or both, groups were nearly identical to the control 20 min later. Fentanyl suppressed the late phase response until 30 min after formalin injection but failed to reduce it thereafter. The numbers of Fos-Ll labelled neurones for groups given nitrous oxide, or halothane, or both, were identical to the control, whereas numbers for fentanyl were 47.2% less (P < 0.01). The decrease occurred predominantly in the neck of the dorsal horn (44.9% of control, P < 0.01) and also in the nucleus proprius and superficial laminae (54.4% and 56.2% of control, P < 0.05). In summary, we found that nitrous oxide, or halothane, or both, did not suppress subsequent spinal sensitization to noxious stimulation. This result supports the previous hypothesis that inhalation anaesthesia lacks pre-emptive analgesic action. Inhalation anaesthetic agents, unlike fentanyl, suppress the early and late phase response because of anaesthetic but not analgesic effects. Thus, we suggest that measuring the genetic product of c-fos proto-oncogene is a useful adjunct to pharmacological tests whenever behavioural hyperalgesia is questionable or unobtainable.

Analysis of nocifensive behavior induced in rats by CO2 laser pulse stimulation.

To characterize nocifensive behavior, a laser beam was applied to the hind footpad of nonanesthetized and unrestrained rats and the reaction pattern was analyzed. Fifty-four rats were divided into nine groups of six animals, and each group was given one of nine combinations of laser stimuli: intensity of 4, 8 or 12 W and duration of 10, 30, or 50 ms. A single pulse was applied to a 0.13 cm2 area of right or left footpad and the trial was repeated 20 times with 3 min between trials. The behavior was videotaped and reviewed for a period of 2 min following each stimulation. It seemed to consist of eight discrete responses, and each response was scored for whether it occurred and for its summed duration per trial. The component responses and the behavior as a whole were characterized by their sensitivity in terms of the level of energy required to attain 50% of the maximum response, and their linear or quadratic trends with increasing stimulus energy. The most sensitive index of pain stimulation was the composite score, followed by foot jumping, foot elevation, body movements, licking, and then foot movements. As stimulus energy increased, rats exhibited a greater number of different responses and a greater frequency of each component response. The results suggest that a pool of hierarchically organized responses in the nocifensive motor system are recruited partially or wholly by nociceptive stimuli of varying intensity.

Spinal pathways of nociceptive information evoked by short CO2 laser pulse in rats.

This study aimed to determine the relative importance of several spinal ascending pathways in conveying laser pulse activated A-delta and C-fiber information by using both awake and anaesthetized rats. Rats were subjected to spinal cord lesion (between T10-T12) under general anesthesia. Three types of lesion were made; dorsal column (DC, n = 4), bilateral dorsal lateral funiculus lesion (DLF, n = 4), and bilateral ventral quandrant lesion (VQ, n = 3). In normal awake rats, a laser pulse (10 watts intensity and 10 ms duration) applied to the plantar surface of the hind foot could evoke two prominent cortical potentials, one early and one late component in the contralateral somatosensory cortex. The early negative potential had a latency of 52.8 +/- 6.8 ms (mean +/- S.E.M.) and amplitude of 0.066 +/- 0.011 mV, while the late component had a latency of 264.6 (4.6 ms and an amplitude of 0.143 +/- 0.014 mV. After DC lesion, only latency of the early response was significantly lengthened (p < 0.05). Latency and amplitude of the early response were reduced markedly (p < 0.01) after bilateral DLF lesion. The change in the late response was significant only in the latency (p < 0.01). The peak amplitude of both early and late responses decreased significantly (p < 0.01) after VQ lesion. In rats with acute preparation, both of the DC and DLF lesions had no significant effect on the laser-evoked late response. The lesion of the VQ completely eliminated the late response.

Dorsal column inhibition of nociceptive thalamic cells mediated by gamma-aminobutyric acid mechanisms in the cat.

Cells in posterior parts of the cat thalamus were investigated. Responses in single units excited by electrical stimulation in the lateral funiculus (LF), the dorsal column nucleus (DCN) or the canine tooth pulp (TP) were analysed. All cells had a spontaneous resting activity which could be increased by extracellular iontophoretic application of DL-homocysteic acid (DLH) and decreased by gamma-aminobutyric acid (GABA). No effect on the spontaneous firing rate was observed following iontophoresis of the selective GABA-antagonists, picrotoxin (GABA-A receptor antagonist) or saclofen (GABA-B receptor antagonist). However, the decreased firing following GABA application was partially blocked by picrotoxin but not by saclofen. A phasic inhibition induced by DCN stimulation in nociceptive thalamic cells is indicated since simultaneous administration of picrotoxin increased the evoked response. This type of inhibitory mechanism could not be detected following LF or TP stimulation. The extracellular activity evoked by electrical stimulation of LF or TP was significantly depressed by preceding electrical stimulation in the DCN. This inhibition was reversed by simultaneous administration of picrotoxin, indicating an involvement of GABA-A receptors. The reversal of the DCN-induced depression of the late responses following LF stimulation occurred after application of saclofen. It is suggested that this effect is partly mediated via GABA-B receptors. Results from the present study indicate an interaction in the thalamus between presumed low-threshold (DCN) and presumed nociceptive afferents (LF and TP) similar to that previously described in the spinal cord.

Spinal antinociception mediated by a cocaine-sensitive dopaminergic supraspinal mechanism.

The role of dopaminergic descending supraspinal processes in mediating the antinociceptive action of cocaine was studied in the rat using a combination of extracellular neuronal recording and behavioral techniques. Neurons in the superficial laminae (I-II) of the spinal dorsal horn with receptive fields on the tail were recorded in anesthetized rats using insulated metal microelectrodes. Stimulation of the receptive field with either high intensity transcutaneous electrical pulses or with an infrared CO2 laser beam produced a biphasic increase in dorsal horn unit discharge. Conduction velocity estimates indicated that the early discharge corresponded to activity in A delta whereas the late response corresponded to activity in C afferent fibers. Cumulative doses of cocaine (0.1-3.1 mg/kg i.v.) inhibited the late response to either electrical or laser stimulation in a dose-related manner. The early response to laser, but not electrical, stimulation was also suppressed by cocaine. Neurons in the spinal dorsal horn with receptive fields on the ipsilateral hindpaw were activated by natural noxious (pinch) or innocuous (tap) somatic stimulation. Cocaine selectively suppressed nociceptively evoked dorsal horn unit discharge. This antinociceptive effect was dose-related (0.3-3.1 mg/kg, i.v.) and antagonized by eticlopride (0.05-0.1 mg/kg, i.v.), a selective D2 dopamine receptor blocker. The same doses of cocaine failed to inhibit the responses of dorsal horn neurons to low threshold innocuous stimulation. Complete thoracic spinal cord transection eliminated the antinociceptive effect of cocaine on dorsal horn neurons and also eliminated the cocaine-induced attenuation of the tail-flick reflex.(ABSTRACT TRUNCATED AT 250 WORDS)

Tooth pulp deafferentation is not associated with changes in primary afferent depolarization of facial afferent endings in the brain stem.

Previous studies have demonstrated that tooth pulp deafferentation is associated with statistically significant alterations in the low-threshold facial mechanoreceptive field properties of brain stem neurons in trigeminal (V) subnucleus oralis. A loss of spinal afferent-induced presynaptic inhibition as a consequence of a decrease in primary afferent depolarization (PAD) following spinal nerve deafferentation has been invoked as a mechanism underlying deafferentation-induced somatosensory neuroplasticity. Therefore, this study was initiated to determine if these pulp deafferentation-induced neuroplastic changes could be accounted for by an alteration in PAD of low-threshold facial afferent endings in subnucleus oralis of anesthetized rats. In control (unoperated) rats (n = 7) and rats (n = 7) that had undergone mandibular pulp deafferentation 6-10 days previously, antidromic compound action potentials evoked by test stimulation in V subnucleus oralis were recorded in branches of the infraorbital (IO) and supraorbital (SO) nerves, and conditioning stimuli were applied to some of the same nerves. PAD of the afferent endings in oralis of these nerve branches was documented in all animals, and there was no significant difference between the two groups in the incidence or any of the other features of PAD. The features of the PAD were consistent with those described in several previous studies of normal animals. These findings indicate that the reported deafferentation-induced loss of spinal presynaptic regulatory mechanisms cannot be entrapolated to all forms of deafferentation injury and that the mechanoreceptive field changes that can occur in central V somatosensory neurons as a result of tooth pulp deafferentation may not reflect an alteration in PAD.

Thalamic nociceptive mechanisms in cats, influenced by central conditioning stimuli.

Field potentials and single cell activity evoked by tooth pulp (TP) stimulation were studied in the ventrobasal (VB) complex of the cat. The experiments were performed using a conditioning-test paradigm. Evoked cell activity or field potentials following TP stimulation was used as a test. Conditioning stimulus was given to different regions of the thalamic central lateral nucleus (CL). Conditioning electrical stimulation in medial (ML 2.8-3.6 mm) parts of CL induced a depression of the TP evoked response in 10 cells. Stimulation sites in lateral CL (ML 3.6-4.2 mm) induced facilitation in eight cells and decreased activity in seven cells. Tooth pulp evoked field potentials in thalamus were facilitated by a preceding stimulation in lateral CL. Cells in the lateral parts of CL are suggested to induce an increased activity in cells in the VB complex which mediate nociceptive information. This effect is suggested to be mediated via a CL induced disinhibition at a reticular thalamic (RE) or at a VB complex level. The medial parts of CL seem to give a traditional feedback inhibition on VB cells. Such an effect is also suggested to be mediated via the RE complex. The importance of these findings are discussed with relation to changes in the thalamus that may occur following long lasting nociceptive stimulation.

Neurophysiological, pharmacological and behavioral evidence for medial thalamic mediation of cocaine-induced dopaminergic analgesia.

These studies examined the effects of cocaine on thalamic neurons that respond maximally either to noxious or to innocuous somatic stimulation. Cocaine attenuated high intensity electrically-evoked nociceptive responses of all 25 units studied in the parafascicular and central lateral nuclei of the medial thalamus. A dose of 1 mg/kg intravenously (i.v.) suppressed medial thalamic unit discharge evoked by both noxious somatic stimulation (49.4 +/- 8.7% of control response) and spinal cord stimulation (76.2 +/- 6.6% of control response). The effect of cocaine on unit responses to noxious somatic stimulation was dose-related in the range of 0.3-3.5 mg/kg i.v. and was attenuated by eticlopride, a D-2 selective dopamine receptor antagonist. Morphine also suppressed noxious somatic evoked responses of medial thalamic units in a dose-dependent manner. Units in the lateral (ventrobasal) thalamus (n = 4) that responded only to innocuous stimuli were not affected by cocaine at doses up to 3.5 mg/kg i.v. Ibotenic acid lesions in the parafascicular nucleus of the medial thalamus attenuated the analgesic effect of cocaine in the formalin test. These results suggest that both cocaine and the parafascicular nucleus interact with dopaminergic mechanisms that attenuate nociceptive spinal projections to the medial thalamus.

Effects of sympathetic stimulation on C-fibre response after peripheral nerve compression: an experimental study in the rabbit common peroneal nerve.

Non-myelinated C-fibre responses during sympathetic trunk stimulation were studied in rabbit common peroneal nerve 2 weeks after the nerve had been subjected to compression at 400 mmHg for 30 min. Our previous studies have demonstrated that during sympathetic trunk stimulation the compound action potential of uninjured somatic C-fibres is characterized by a reduced amplitude and an increased latency. In the present study, nerve compression changed the C-fibre response to sympathetic stimulation. Three out of eight nerves reacted to nerve compression by increased C-fibre compound action potential amplitude in response to sympathetic stimulation. In three other rabbits with compressed nerves the C-fibre action potential amplitude was unchanged, and in the remaining two rabbits the action potential amplitude was decreased during sympathetic stimulation. The action potential latency increased in all tested compressed C-fibres. The phenomenon of increased C-fibre amplitude during sympathetic activation has not been observed in uninjured nerves. As in uninjured nerves, noradrenaline infusion produced an increased C-fibre action potential amplitude and latency in six animals. Sympathetic stimulation did not affect the A-fibre response. These results indicate that sympathetic activity influences the conduction properties in C-fibres of somatic origin and that the response can be changed after a nerve injury. The findings may be of importance for the understanding of pain aggravation in different types of nerve injuries during increased sympathetic activity.

Properties of single neurons in the cat midsuprasylvian gyrus.

Responses of cells in the midsuprasylvian gyrus (MSSG) of cats were investigated following electrical stimulation of the central lateral nucleus (CL) of the thalamus and tooth pulp, low-threshold cutaneous or visual afferents. Electrical stimulation in CL induced excitation in many cells located in cortical areas 5 and 7. Cells in these areas also received input from somato-sensory and visual afferents. Cells in MSSG showed a wide convergence from tooth pulp, low-threshold cutaneous afferents and from the CL. The majority of wide convergent cells in area 5 were found in layers IV and V, while cells excited by CL and tooth pulp were found in layers II and III. Similarities were found between CL and tooth pulp evoked responses with regard to the excitation-inhibition pattern. The excitation evoked from CL and tooth pulp was less often followed by a hyperpolarizing potential compared to that seen after low-threshold lip, paw and visual afferent stimulation. Stimulation sites in the lateral parts of CL-evoked responses with the shortest latencies in area 5. In this part of the cortex, short latency synaptic potentials were found in cells in superficial layers. In the same area, synaptic potentials of short latency were also evoked by electrical stimulation of tooth pulp, lip and paw. Light-flash stimulation evoked responses with the shortest latencies in area 7. The results of this study demonstrate that putative nociceptive information reaches the parietal association cortex and that part of this input may be relayed via CL. We suggest that the excitatory influences of nociceptive and CL stimulation is related to behavioral arousal and attention mechanisms.

Field potential analysis of the cortical projection of the central lateral nucleus in the cat.

A previous field potential study has indicated a monosynaptic projection of fibres from the central lateral nucleus (CL) to the mid-suprasylvian gyrus (MSSG). The present study, which is based on an analysis of current source density (CSD), aims to investigate further the sites of major localized synaptic activities in different layers of the MSSG after electrical stimulation in the CL. An initial positive surface potential was evoked in the MSSG with a latency of 3-5 ms and followed by a large negative potential with a peak latency of 8-15 ms. The initial positivity was only found in the rostral part of the MSSG, which corresponds to area 5. The positivity reversed in deeper layers. The CSD analysis showed a sink at a depth from 650 to 1050 microns. A corresponding source was found more superficially at 400-600 microns. This indicates that CL fibres have an excitatory synaptic termination on the soma or proximal dendrites of neurons in layers III and IV. The surface negative potential reversed at the border between layers II and III, suggesting a superficial CL projection. The CSD analysis of potentials in superficial layers showed a sink appearing between the pial surface and a depth of 350 microns, and a source lying in layers below. This indicates a depolarization of apical dendrites of cells in layers II and III. The superficial sink appeared in a large part of the MSSG. Application of a solution of 0.5% gamma-aminobutyric acid (GABA) on the surface of the cortex blocked the superficial sink and source and revealed a prominent sink current in layers III and IV in agreement with a deep termination of CL fibres. Application of a solution of 25 mM DL-2-amino-5-phosphono-valeric acid (APV) abolished CL-evoked cortical responses indicating that N-methyl-D-aspartate (NMDA) receptors are involved in the cortical activation. The CSD analysis confirms that CL has a wide superficial projection to the MSSG. It also confirms a deeper monosynaptic projection from CL to area 5.