Dorsal raphe stimulation, 5-HT and morphine microiontophoresis effects on noxious and nonnoxious identified neurons in the medial thalamus of the rat

In single cell experiments, the characterization of the responses of medial thalamic neurons to noxious and nonnoxious stimulation was made to examine the effects of two substances involved in pain, morphine and 5-HT, and the action of one pain suppressor mechanism, dorsal raphe stimulation. Single cell activity was recorded in urethane anesthetized rats. Tail pinch and tail immersion in hot water were used as nociceptive stimuli. Skin strokes, air puffs and hair brushing were used as nonnociceptive stimuli. Morphine, 5-HT microiontophoresis and dorsal raphe stimulation were performed in all the recorded units. Fifty-eight percent from 61 medial thalamic recorded units responded both to noxious and nonnoxious stimulation; whereas only 18% and 24.6% of the units responded exclusively to noxious and nonnoxious stimulation, respectively. The noxious responding units were located in the most posterior portions of the medial thalamus. Dorsal raphe stimulation and 5-HT ejection prevented the excitation elicited by noxious input. Morphine ejection prevented both the noxious and nonnoxious input in medial thalamus, in a different population as compared to dorsal raphe stimulation or 5-HT ejection. These findings support the existence of a pain ascending mechanism mediated by an opioid-serotonergic interaction in the medial thalamus of the rat.     

Coding of peripheral electrical stimulation frequency in thalamocortical pathways

Frequency information of the environment is an important feature for sensory perception. It has been demonstrated that cortical and thalamic neurons exhibited frequency-specific responses to peripheral stimulation. In the present study, we investigated the effects of 1-100 Hz peripheral electrical stimulations on various thalamic and cortical areas in awake rats. We used chronically implanted microelectrode arrays to record neural activities from the anterior cingulate cortex, primary somatosensory cortex, and medial dorsal and ventral posterior thalamus. The results revealed that cortical and thalamic neurons exhibited frequency-specific responses at both single-neuron and ensemble levels. Clusters of neurons responded to different frequency ranges with changes of both the peak firing rates and the phases of the peak responses in a stimulation cycle. Partial directed coherence analysis showed that information flowing between these recorded areas is also enhanced or inhibited in some frequency-specific pattern during stimulation. These evidences suggest that central nervous system may code environmental frequency information mainly with the activation of selected neural circuits according to their own intrinsic electrical properties. These properties, in turn, may facilitate or inhibit their responses when stimulation with specific frequency information arrives.     

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.     

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.     

Periaqueductal gray inhibition of trigeminal subnucleus caudalis unitary responses evoked by dentine and nonnoxious facial stimulation

The possible pain inhibitory effects of periaqueductal gray (PAG) stimulation were investigated in cats anesthetized with Nembutal and immobilized with Flaxedil. Unitary responses evoked by electrical stimulation of the upper canine dentine and by cutaneous facial noxious and nonnoxious stimuli were recorded extracellularly from the trigeminal subnucleus caudalis. A bipolar electrode was introduced into the PAG to test the effects of PAG excitation on the trigeminal response to dentine (TRED) and cutaneous nonnoxious stimulation. In some experiments, a similar electrode was lowered into the contralateral posterior thalamus to study the antidromic activation of subnucleus caudalis cells and the effects of thalamic stimulation on the TRED. Dentine stimulation evoked brief (6- to 15-ms) bursts of 1 to 10 spikes with 3- to 25-ms latencies. Most units (88%) were also activated by cutaneous facial stimulation. Stimulation of the posterior thalamus had no effect on the TRED or on responses to cutaneous stimulation, but activated antidromically 10% of the units. In 71% of the units PAG stimulation inhibited the TRED. In some of those cases (12%), the inhibitory effect persisted 30- to 60 s. The PAG stimulation could produce paradoxical effects, potentiating the TRED evoked by threshold intensity and inhibiting the TRED elicited by suprathreshold stimulation. About one-half the PAG points evoked detectable effects. Their location had no clear topographical distribution, although ventral sites were more potent than dorsal sites. Responses evoked by nonnoxious facial stimulation were also inhibited by the PAG.     

Effects of thalamic parafascicular stimulation on the periaqueductal gray and adjacent reticular formation neurons. A possible contribution to pain control mechanisms

To investigate the mechanism of analgesic effect of electrical stimulation of the thalamic parafascicular nucleus (Pf), we studied modulations of neuronal activities in the periaqueductal gray (PAG) and the adjacent reticular formation (RF) in response to Pf electrical and peripheral noxious stimulations in the rat. Extracellular single unit activities were recorded from 129 neurons in the PAG and adjacent RF under light halothane anesthesia. Pf stimulation caused neuronal responses in approximately 80% of the PAG and adjacent RF neurons, and noxious stimulation in 75%, with predominant excitatory responses to either stimulation. When the responses to the two stimuli were tested in the same neurons (n = 69), 91% responding to noxious stimuli also responded to Pf stimuli, again with predominant excitatory responses to either stimulation. The PAG and adjacent RF neurons that were verified antidromically to project to the nucleus raphe magnus (NRM), showed a similar pattern of response (n = 20). These results suggest that a sizeable population of neurons in the PAG and adjacent RF receives excitatory effects from the Pf and noxious afferents, and that part of these neurons projects to the NRM, which inhibits the dorsal horn cells of the spinal cord (the descending pain suppression system). Thus, part of the mechanism of the analgesic effects of Pf stimulation is due to activation of the descending pain suppression system by exciting the PAG and adjacent RF neurons. A possible role of noxious afferents on the negative feedback to pain mediation through this descending system also has to be considered.     

Responses of thalamic and hypothalamic neurons to scrotal warming in rats: Non-specific responses?

Activities of thalamic and hypothalamic neurons in response to scrotal temperature change were investigated in urethanized (1.2-1.5 g/kg) rats with special attention to changes in cortical electroencephalogram (EEG). Somatosensory relay neurons were identified electrophysiologically in the ventrobasal complex (VB) of the thalamus. These neurons had tactile receptive fields in areas outside the scrotum. Forty out of 44 of these neurons responded to scrotal warming by increase in firing rate. The responses occurred abruptly at threshold temperatures ranging from 31 to 40 degrees C (switching response) with simultaneous changes in EEG from high to low voltages (desynchronization). In both the thalamus and the hypothalamus, neurons excited or inhibited by scrotal warming were also excited or inhibited, respectively, by noxious stimulation that produced EEG desynchronization. Neurons showing no response to scrotal warming were not affected by noxious stimulation. In deeply anesthetized (2.5 g/kg urethane) rats, VB relay neurons responded to tactile stimulation of their receptive fields, but scrotal warming produced no change in either EEG or activities of thalamic and hypothalamic neurons. These facts suggest that the responses of thalamic and hypothalamic neurons to scrotal warming may be 'non-specific'. Most thalamic and hypothalamic neurons showing switching responses did not appear to mediate specific information concerning scrotal skin temperature.     

Differential modulation of nociceptive neural responses in medial and lateral pain pathways by peripheral electrical stimulation: a multichannel recording study

It is well accepted that peripheral electrical stimulation (PES) can produce an analgesic effect in patients with acute and chronic pain. However, the neural basis underlying stimulation-induced analgesia remains unclear. In the present study, we examined the pain-related neural activity modified by peripheral stimulation in rats. The stimulation frequency of pulses applied to needle electrodes in the hindlimb was 2 Hz alternating with 100 Hz, with 0.6 ms pulse width for 2 Hz and 0.2 ms for 100 Hz. The intensity of the stimulation was increased stepwise from 1 to 3 mA with each 1-mA step lasting for 10 min. The nociceptive neural and behavioral responses were examined immediately after the termination of stimulation. Using a multiple-channel recording technique, we simultaneously recorded the activity of many single neurons located in the primary somatosensory and anterior cingulate cortex (ACC), as well as the ventral posterior and medial dorsal thalamus in behaving rats. Our results showed that peripheral electrical stimulation significantly reduced the nociceptive responses in ventroposterior thalamus and somatosensory cortex, indicating an inhibition of nociceptive processing. In contrast, the analgesic stimulation produced a significant increase in mediodorsal thalamus while a less significant decrease in cingulate cortex, reflecting a complicated effect associated with combined antinociceptive activation and nociceptive suppression. These results support the idea that peripheral electrical stimulation can ultimately alter the pain perception by specifically inhibiting the nociceptive transmission in the sensory pathway while mobilizing the antinociceptive action in the affective pathway, thus to produce pain relief.     

Bulbar influences on the periaqueductal gray. Potential role in nociception

Unit activity was recorded from 96 neurons in the periaqueductal gray (PAG) in response to focal electrical stimulation of the lateral reticular nucleus (LRN) and the nucleus gigantocellularis (NGC), in anesthetized, curarized rats. Consistent with anatomical studies showing direct projections from these nuclei to PAG, short latency excitatory responses (less than 5 ms) were found in 63 neurons and inhibition of the activity in 28 neurons. Peripheral noxious heat stimulation was effective in altering the activity in 36 of these neurons (38%). The LRN and NGC stimuli inhibited the noxious evoked responses in 26 of these neurons. The inhibition could also be induced when the dorsolateral funiculi (DLFs) were cut. These results indicate that LRN and NGC can have a direct influence on PAG neurons, which are probably involved in the processing of noxious information.     

Thalamic components of the ascending vestibular system

A combined anatomical and physiological approach was used to identify the thalamic nuclei that relay vestibular activity to the cerebral cortex at short latency in the cat. For the anatomical experiments, electrical stimulation was applied to the vestibular nerve, the cortical sites showing maximal amplitude responses were defined, and horseradish peroxidase was injected in these sites. Two days later, the animals were killed and brain sections were processed to localize enzyme reaction products in thalamic neurons. After either anterior suprasylvian injection or posterior cruciate region injection, most labeled neurons were in the ventral posterolateral nucleus. A few labeled neurons were found in the intralaminar and posterior groups of nuclei. In separate physiological experiments, responses to vestibular nerve stimulation and cerebral cortical stimulation were recorded from the thalamus. Short-latency (<3.5 ms), large-amplitude evoked potentials from vestibular nerve stimulation and antidromic field potentials from cortical stimulation were recorded within the ventral basal complex and the most rostral portions of the posterior group of thalamic nuclei. These data indicate that neurons in the ventral basal complex and the region between the ventral basal complex and the posterior group relay vestibular activity to both the anterior suprasylvian and posterior cruciate regions of the cerebral cortex.     

Intracellular responses of raphe magnus neurons during the jaw-opening reflex evoked by tooth pulp stimulation

Neurons in the nucleus raphe magnus (RM) may play an important role in the modulation of nociception. To determine how RM neurons are activated during a nociceptive reflex, the intracellular responses of raphe neurons were studied during the jaw-opening reflex (JOR) elicited by tooth pulp shock in lightly anesthetized cats. Tooth pulp stimulation produces reflex EMG activation of the digastric muscle at a latency of 7-11 ms, resulting in jaw opening. Tooth pulp shock that elicits the JOR also produces an EPSP in a subset of raphe neurons. This EPSP consists of an early small depolarization that occurs at a latency of 10-15 ms followed by a larger depolarization at a latency of 20-60 ms. In all cases the latency to EPSP is longer than the latency to digastric EMG onset. Electrical stimulation of the 4 paws elicits oligosynaptic EPSPs in the same cells at a latency of 16-20 ms. Electrical train stimulation of the midbrain periaqueductal gray region (PAG) suppresses the JOR. Single shock stimulation at the same PAG sites that suppress the JOR evokes monosynaptic EPSPs in the large majority of raphe neurons recorded. In all cases, the threshold for EPSP is below the threshold for suppression of the JOR. The EPSP amplitude is a direct function of PAG stimulus intensity and there is temporal summation of EPSPs evoked by paired PAG shocks. At condition-test intervals of 40-90 ms, train stimulation of PAG suppresses the tooth pulp-evoked EPSP in raphe neurons. The threshold for EPSP suppression occurs at a PAG stimulation intensity below that required for suppression of the JOR. The present findings provide evidence that RM neurons may play an important role in the modulation of the tooth pulp-evoked JOR, but only after the initial withdrawal reflex has occurred.     

Reactions of medial geniculate body neurons to stimulation of the auditory cortex]

Extra- and intracellular responses of pars principalis neurons in the medial geniculate body to stimulation of the first (AI), second (AII) and third (AIII) auditory cortex were studied in experiments on cats immobilized with d-tubocurarine. In geniculate neurons both antidromic (45-50%) and orthodromic (50-55%) reactions occurred in response to the auditory cortex stimulation. The latencies for antidromic and orthodromic responses were 0.3-2.5 ms and 2.0-ms, respectively. Late responses appeared with a latency of 30-200 ms. 63% of neurons responded antidromically to both AII and AI stimulation, that confirms the suggestion on the projection of a considerable number of the geniculate neurons to both auditory zones. Orthodromic responses of geniculate neurons consisted either of 1-2 spikes or a burst of 8-12 spikes with a frequency of 300-600/sec. The bursts are supposed to be the responses of inhibitory geniculate neurons. Intracellular recording showed the following responses: antidromic spikes, EPSP, EPSP-spike, EPSP-spike-IPSP, EPSP-IPSP and initial IPSP. Above 50% of initial IPSPs had the latency of 2.0-4.0 ms. They are supposed to be produced with the participation of intermediate inhibitory neurons located in the medial geniculate body.     

Regulation of slow potential shifts in nucleus reticularis thalami by the mesencephalic reticular formation and the frontal granular cortex.

Novel stimuli or electric stimulation of the mesencephalic reticular formation (MRF) produced large positive slow potentials (SPs) in rostral nucleus reticularis thalami (RVA) that accompanied the negative SPs known to occur in frontal cortex. SP durations (20-30 sec) were similar to the periods of unit inhibition that occur in RVA following MRF stimulation. Trains of 8 c/sec medial thalamic stimuli produced phasic negative SPs in RVA similar in duration to the intervals of unit excitation that follow each stimulus pulse. These results suggest that the polarity and duration of the SPs in RVA reflect changes in excitation of the underlying neurons. Direct activation of a specific region of RVA produced complete inhibition of visual cortex responses evoked by optic tract stimuli, a finding which suggests that RVA has an inhibitory action on the thalamus. A tone reinforced by electric shock also elicited SPs in frontal cortex (negative) and RVA (positive). In contrast to the long duration of the MRF- or novelty-elicited SPs, the durations of the conditioned SPs were phasic and were regulated by the tone--shock interval. Bilateral cryogenic blockade of the interconnections between the frontal cortex and medial thalamus abolished SPs of all origins in the frontal cortex. The blockade also abolished conditioned SPs in RVA, but did not affect the MRF-elicited ones. Thus, the subcortical SPs that accompany orienting to novel stimuli are distinct from those which occur during the higher cognitive process of conditioned expectancy and require the integrity of the mediothalamic-frontocortical system.     

Nucleus basalis stimulation facilitates thalamocortical synaptic transmission in the rat auditory cortex

Nucleus basalis (NB) neurons are a primary source of neocortical acetylcholine (ACh) and likely contribute to mechanisms of neocortical activation. However, the functions of neocortical activation and its cholinergic component remain unclear. To identify functional consequences of NB activity, we have studied the effects of NB stimulation on thalamocortical transmission. Here we report that tetanic NB stimulation facilitated field potentials, single neuron discharges, and monosynaptic excitatory postsynaptic potentials (EPSPs) elicited in middle to deep cortical layers of the rat auditory cortex following stimulation of the auditory thalamus (medial geniculate, MG). NB stimulation produced a twofold increase in the slope and amplitude of the evoked short-latency (onset 3.0 ± 0.13 ms, peak 6.3 ± 0.21 ms), negative-polarity cortical field potential and increased the probability and synchrony of MG-evoked unit discharges, without altering the preceding fiber volley. Intracortical application of atropine blocked the NB-mediated facilitation of field potentials, indicating action of ACh at cortical muscarinic receptors. Intracellular recordings revealed that the short-latency cortical field potential coincided with a short-latency EPSP (onset 3.3 ± 0.20 ms, peak 5.6 ± 0.47 ms). NB stimulation decreased the onset and peak latencies of the EPSP by about 20% and increased its amplitude by 26%. NB stimulation also produced slow membrane depolarization and sometimes reduced a long-lasting IPSP that followed the EPSP. The combined effects of NB stimulation served to increase cortical excitability and facilitate the ability of the EPSP to elicit action potentials. Taken together, these data indicate that NB cholinergic neurons can modify neocortical functions by facilitating thalamocortical synaptic transmission. © 1993 Wiley-Liss, Inc.     

Electrophysiology and Pharmacology of the Corticothalamic Input to Lateral Thalamic Nuclei: an Intracellular Study in the Cat

Though most experimental evidence indicates that the corticothalamic (CT) pathway would exert a direct excitatory action on thalamic relay neurons, the electrophysiological features of this excitation have never been clearly described. A methodological problem in previous electrophysiological studies was that direct corticofugal effects on relay cells could not be separated from those mediated by collateral activation of reticular thalamic neurons. In the present study, the reticular complex was lesioned by kainic acid and the CT response of relay neurons of the ventral lateral nucleus was recorded intracellularly in cats under pentobarbital or urethane anaesthesia. Following reticular thalamic lesions, a prominent depolarization was triggered in thalamic relay cells by stimulation of the CT pathway. This depolarization strongly drove spike discharges, and its amplitude augmented when the stimulation rate exceeded 2 Hz. Tetanizing the CT input with short trains (100 - 200 Hz for 200 - 300 ms) produced a similar augmentation to test volleys for 15 - 30 s after the tetanos. The CT excitation and its frequency-dependent augmentation were depressed by ketamine injection or by local application of N-methyl-D-aspartate (NMDA) antagonists. The augmenting phenomenon appeared strictly homosynaptic. For instance, it did not appear during repetitive stimulation of the cerebellar input, nor did the CT input potentiate subthreshold synaptic potentials of cerebellar origin during a conditioning procedure. Conversely, the cerebellar excitation was depressed when it occurred during the CT depolarization. It is concluded that the direct synaptic responses induced by CT fibres in relay neurons are mediated at least partly by the activation of NMDA receptors. Moreover, the marked non-linear additivity of cerebellar and CT synaptic potentials raises questions concerning the presumed improvement of thalamic transmission of peripheral informations ensured by the CT input. Instead, both inputs could compete for control of the firing of thalamic neurons. The numerical importance of CT fibres and the strong augmenting mechanism operating at synaptic sites in the thalamus suggest that the role of the thalamus is not only to transfer peripheral informations toward the cortex, but also and mainly to feed back to the cortex a modified copy of its own neuronal constructs.     

Noxious and non-noxious responses in the medial thalamus of the rat

Single-cell experiments were undertaken to localize and characterize the medial thalamic (MT) neurons which respond to noxious and non-noxious input in the rat. The observations demonstrated that: (1) 61 and 42% of MT neurons respond to noxious (Nox) and non-noxious (NN) stimulation, respectively; (2) MT neurons exhibit 4 cell types according to their pattern of response; Type A units were excited exclusively by Nox stimulation; Type B units were excited exclusively by NN stimulation; Type C units were excited by both (Nox and NN) stimulation, and Type D units exhibited decreases in firing rate following both stimulation modalities; (3) neurons of the parafascicularis nucleus exhibit more noxious responses (Type A units) than other medial thalamic areas.     

Thalamic modulation of visceral nociceptive processing in adult rats with neonatal colon irritation

Visceral pain originates from visceral organs in response to a noxious stimulus which, if prolonged, may lead to chronic changes in the neural network mediating visceral nociception. For instance, colon inflammation enhances the responses of neurons in the thalamus to colorectal distension (CRD), whereas lesion in the dorsal column (DC) reverses this neuronal sensitization, suggesting that the thalamus and the DC play major roles in chronic visceral pain. In this study, we used adult rats sensitized with neonatal painful colon irritation to reveal the contribution of the thalamus and the DC to neuronal hyperexcitability in a model of chronic visceral pain. We recorded the responses of lumbosacral neurons to CRD in control rats and in rats with colon irritation following stimulation or inactivation of the thalamus, and after DC lesion. Our results show that, first, neuronal responses to CRD decreased following thalamic stimulation in control rats, whereas, in rats with colon irritation, responses either decreased or increased; second, DC lesion attenuated or enhanced these effects in the positively or in the negatively modulated group of neurons, respectively; third, lidocaine injection in the thalamus reduced the responses to CRD in some of the neurons recorded in rats with colon irritation, but had no effect on those in control rats. Therefore, it is reasonable to speculate that plasticity in rats with colon irritation that may underlie chronic pain is sustained by feedback loops ascending in the DC and engaging the thalamus.     

Inhibitory influence of the mesocortical dopaminergic system on spontaneous activity or excitatory response induced from the thalamic mediodorsal nucleus in the rat medial prefrontal cortex

Since the medial prefrontal cortex receives converging projections from the mediodorsal nucleus of the thalamus (MD) and the dopaminergic neurons located in the ventromedial mesencephalic tegmentum (VMT) the responses of cortical neurons to ipsilateral VMT and MD stimulation (50–150 μA; 0.2–0.5 ms duration) were analyzed in ketamine anaesthetized rats. MD stimulation at 1 Hz blocked the firing of 90% of the spontaneously active cortical units tested (mean latency, 15 ms; mean duration, 182 ms). MD stimulation at 5–10Hz evoked single spike responses (mean latency, 16 ms) in 80% of the units tested. Ten to 15 days after kainic acid injection into the MD the number of cortical neurons inhibited (1 Hz) or excitated (5–10 Hz) was reduced to 57 and 18%, respectively. Following stimulation of the VMT (at a frequency of 1–5 Hz), 85% of cortical neurons showed an arrest of spontaneous firing occurring after a mean latency of 17 ms and lasting 109 ms on the average. Most of the cells displaying the VMT inhibitory effect were excitated by MD stimulation. Moreover VMT stimulation, applied 3–45 ms before that of MD, blocked the excitation induced by MD in 75% of the units tested. After injection of 6-hydroxydopamine into the medial forebrain bundle or intraperitoneal administration of α-methyl-paratyrosine (α-MpT), the number of units tested responding to VMT stimulation was of 19 and 35%, respectively. Moreover in these treated rats, the proportion of excitatory responses to MD blocked by VMT stimulation was reduced to 5 and 6%. On the other hand, the effects induced by VMT stimulation were not affected after specific destruction of the noradrenergic ascending system. These results suggest that the mesocortical dopaminergic neurons modulate the influence of the main thalamic afferent on the prefrontal cortical cells.     

Systemically administered cocaine alters stimulus-evoked responses of thalamic somatosensory neurons to perithreshold vibrissae stimulation

Previous studies have shown that systemically administered cocaine can transiently alter responses of primary somatosensory cortical neurons to threshold level stimulation of peripheral receptive fields. The goal of the present investigation was 2-fold: (1) characterize the effects of systemic cocaine on stimulus-evoked responses of the ventral posterior medial (VPM) thalamic neurons which relay somatosensory information to the cortex and (2) determine the time course and magnitude of changes in monoamine levels within the somatosensory thalamus following systemic administration of cocaine. Extracellularly recorded responses of single VPM thalamic neurons to whisker stimulation were monitored before and after cocaine administration in halothane anaesthetized rats. Each cell was first characterized by assessing its response profile to a range of perithreshold level deflections of the optimal whisker on the contralateral face. Drug effects on stimulus-response curves, response magnitude and latency were determined from quantitative analysis of spike train data. The results indicate that cocaine elicits a predictable augmentation or attenuation of the sensory response magnitude, with the direction of the change inversely related to the initial magnitude of the stimulus-evoked discharge. In addition, cocaine consistently reduced the response time of somatosensory thalamic neurons to peripheral receptive field stimulation. At the same dose and over the same time period, cocaine also produced marked elevation of norepinephrine and serotonin levels within the ventrobasal thalamus, as determined by in vivo microdialysis. These results suggest that cocaine-induced increases in norepinephrine and serotonin are responsible for drug-related modulation of the transfer of sensory signals through primary thalamocortical relay circuits.     

Excitatory projection of the rat subicular complex to the cingulate cortex and synaptic integration with thalamic afferents

We studied the responses of rat cingulate cortex neurons to electrical stimulation of the subicular complex. Intracellular and 'quasi-intracellular' recordings from layer V posterior cingulate neurons showed that stimulation of the presubiculum or postsubiculum evoked EPSPs and action potentials. These were usually followed by shallow IPSPs averaging 122 ms in duration. Frequency potentiation of an EPSP was demonstrated in one case. Laminar analysis of field potentials provided evidence for a source of excitatory synaptic drive in layer II-III of the posterior cingulate cortex, where the subicular projections terminate, presumably on apical dendrites of layer V pyramids. Intracellular HRP injection of neurons showing EPSPs after subicular complex stimulation established that these responsive neurons were layer V pyramids. One cell with physiological properties characteristic of inhibitory interneurons was recorded in layer V. Stimulation of the thalamic nuclei lateralis and anterior ventralis also evoked EPSPs and action potentials in layer V cingulate neurons. In one cell it was possible to show that EPSPs evoked by presubicular stimulation and by nucleus anterior ventralis summed. These results indicate that subicular and thalamic afferents make excitatory synaptic contact onto dendrites of the same layer V cingulate neurons; that spatial summation can integrate the input from these two sources; and that inhibition from local interneurons limits the duration of this excitatory influence.