Ventrobasal Thalamus Research Articles

Ultrastructural study of external cuneothalamic neurons and their synaptic relationships with primary afferents in the gerbil.

The present study examined the synaptic organization of external cuneothalamic neurons and their relationships with primary afferents in the gerbil external cuneate nucleus (ECN) following an injection of horseradish peroxidase (HRP) into the anterodorsal cap of the ventrobasal thalamus in conjunction with a simultaneous injection of HRP into the contralateral brachial and cervical nerve plexuses. The thalamus-projecting neurons have been shown to be confined to the intermediate portion of the caudal half of the ECN at the light microscopic level (Lan et al., 1994c). In this study, HRP-labelled external cuneothalamic neurons were ultrastructurally characterized by their relatively small-sized soma bearing a variable number of somal spines. Their nucleus had a slightly indented contour with an eccentric nucleolus. The HRP-labelled somata were postsynaptic to many axon terminals, which were classified into round (Rs type; 53.0%), pleomorphic (Ps type; 32.7%), and flattened (Fs type; 14.3%) vesicle-containing boutons. The HRP-labelled dendritic elements were postsynaptic to a greater number of axon terminals, which were also classified into the round (Rd; 64.7%), pleomorphic (Pd; 25.2%), and flattened (Fd; 10.1%) type boutons. These presynaptic axonal boutons tended to synapse on distal and secondary dendrites of external cuneothalamic neurons. In the present simultaneous HRP labelling study, some of the primary afferent terminals made direct synaptic contacts with the dendrites of the external cuneothalamic neurons. In view of the multiple inputs onto the external cuneothalamic neurons, impinging particularly on their somata and secondary dendrites, it is suggested that the proprioceptive information reaching these neurons is intensively modulated and integrated before transmission ultimately to the cerebral sensorimotor cortex.

Capsaicin-induced rapid receptive field reorganization in cuneate neurons.

1. To determine whether activity in unmyelinated or thinly myelinated primary afferents affects the organization of cutaneous receptive fields (RFs) in the cuneate nucleus, subcutaneous injections of capsaicin were made into the RFs of cuneate neurons in anesthetized cats. The effects of capsaicin injection on RF size and position, response properties, and spontaneous firing rates were determined during single-unit recordings. 2. Subcutaneous injection of capsaicin (10% dissolved in 70% ethanol) into peripheral RFs produced rapid RF reorganization in all neurons tested (n = 20), even when the original RF remained responsive to tactile stimulation. RF reorganization was marked by the appearance of newly responsive RFs. These RFs appeared as either contiguous expansions of the original RF or as new, noncontiguous fields. Control injections of the vehicle alone never produced RF reorganization (n = 9). RF reorganization was not related to changes in spontaneous activity. 3. Following capsaicin-induced RF reorganization, subcutaneous injections of lidocaine were made into the original RFs (n = 8). These injections produced no additional RF reorganization in seven of the eight neurons, even though in each case the lidocaine injections produced at least partial blocks of responsiveness from within the original RF. 4. In approximately one-half of the neurons (9 of 20), the reorganized RFs had response properties that were different from those of the original RF. This result suggests that, for neurons in the dorsal column nuclei (DCN), physiological mechanisms that normally mask inputs and restrict RF size can give rise to response specificity. 5. The results of these experiments demonstrate that capsaicin-induced RF reorganization, which has been reported previously in ventrobasal thalamus and primary somatosensory cortex, can arise within the dorsal column-medial lemniscal system, at the level of the DCN. The present results also provide evidence that rapid RF reorganization in cuneate neurons can be produced by blockade of a subset of peripheral afferents that are sensitive to capsaicin.

Antagonism of the presumed presynaptic action of l-AP4 on GABAergic transmission in the ventrobasal thalamus by the novel mGluR antagonist MPPG

The metabotropic glutamate receptor (mGluR) agonists CCG-I and l-AP4, acting at Group II and Group III mGluRs respectively, can reduce GABAergic synaptic inhibition on single neurones in the rat thalamus in vivo via a presumed presynaptic mechanism. The actions of l-AP4 were antagonized by (±)-α-methyl-4-phosphonophenylglycine (MPPG), whereas CCG-I was significantly less affected. Thus MPPG may be a useful tool for detecting physiological roles for Group III mGluRs.

GABA B-activated gK + in thalamic neurons in the lethargic ( [formula omitted]) mouse model of generalized absence seizures

Whole-cell voltage-clamp recordings were made from thalamic ventrobasal (V13) neurons of age-matched lethargic ( lh lh ) and wildtype (+/+) mice. Hyperpolarizing voltage commands (40 mV) from a holding potential of −60 mV were delivered to the cell and the resulting K + conductance ( gK +) activated by the GABA B receptor agonist baclofen was measured and compared between the two groups. VB cells from +/+ and lh lh displayed no significant differences in resting conductance ( gIN) or gK + activated by baclofen. In addition to this, isolated, evoked GABA B-mediated currents were recorded in VB cells. There was no significant difference in peak amplitude or latency to peak noted between the two groups. These data suggest that postsynaptic GABA B receptor-mediated function is not altered in VB thalamic neurones in this model of absence seizures.

Development of firing patterns and electrical properties in neurons of the rat ventrobasal thalamus

The electrophysiological properties of thalamic neurons of the rat ventrobasal complex (VB) in vitro were studied during early postnatal development. Current clamp recordings using the whole cell patch clamp method revealed that immature thalamic neurons had less negative membrane potential and higher input resistance than mature neurons. One of the most remarkable differences was the absence of spike bursts riding on the low threshold calcium spike (LTS) in VB neurons before postnatal day 12 (P12). Action potentials recorded from immature neurons had longer duration than those of mature cells and were followed by a longer afterhyperpolarization (spike-ahp). The spike-ahp became shorter as maturation progressed, reaching mature characteristics around P12, coinciding with the appearance of spike bursting on the LTS. The calcium activated potassium conductance, I C, played a prominent role in the spike-ahp in immature neurons. In conclusion, the major differences in intrinsic membrane properties of VB neurons occur during the first 12 postnatal days. The appearance of spike bursting riding on the LTS at P12 is consistent with the emergence of synchronized thalamocortical oscillations in rats around that age.

Localization of alpha 7 nicotinic receptor subunit mRNA and alpha-bungarotoxin binding sites in developing mouse somatosensory thalamocortical system.

Previous studies in rat, showing a transient pattern of expression of the alpha 7 nicotinic acetylcholine receptor in the ventrobasal thalamus and barrel cortex during the first 2 postnatal weeks, suggest that these receptors may play a role in development of the thalamocortical system. In the present study, in situ hybridization and radiolabeled ligand binding were employed to examine the spatiotemporal distribution of alpha 7 mRNA and alpha-bungarotoxin binding sites in the thalamocortical pathway of mouse during early postnatal development. As in the rat, high levels of alpha 7 mRNA and alpha-bungarotoxin binding sites are present in the barrel cortex of mouse during the first postnatal week. Both alpha 7 mRNA and its receptor protein are observed in all cortical laminae, with the highest levels seen in the compact cortical plate, layer IV, and layer VI. When viewed in a tangential plane, alpha 7 mRNA and alpha-bungarotoxin binding sites delineate a whisker-related barrel pattern in layer IV by P3-5. Quantitative analysis reveals a dramatic decrease in the levels of expression of alpha 7 mRNA and alpha-bungarotoxin binding sites in the cortex by the end of the second postnatal week. Unlike in the rat, only low levels of alpha 7 mRNA or alpha-bungarotoxin binding sites are present in the ventrobasal complex of the mouse thalamus. The broad similarities between the thalamocortical development of rat and mouse taken together with the present results suggest that alpha 7 receptors located on cortical neurons, rather than on thalamic neurons, play a role in mediating aspects of thalamocortical development.

Calcium influx in rat thalamic relay neurons through voltage-dependent calcium channels is inhibited by enkephalin

High and low voltage-activated, transient (HVA and LVA,T) Ca 2+ currents are crucial in determining the characteristic thalamic firing pattern, during the oscillatory mode. The modulatory effects induced by d-ala 2- d-leu 5-enkephalin (DADLE) on voltage-dependent Ca 2+ channels have been investigated on acutely dissociated neurons from rat ventro-basal (VB) thalamus, by means of whole cell patch-clamp technique. DADLE (400 nM) reduced HVA Cat+ channel currents in 37 out of 44 cells tested (−53 ± 5.3% to 0 mV test potential, n = 24,). In 50% of the cases DADLE induced an effect which was persistent at all the potentials tested, i.e. a voltage-independent one. In the remaining neurons, the inhibition partially or totally disappeared on the currents evoked at the highest potentials. DADLE was also able to inhibit LVA Ca 2+ channels (−40% in five out of 12 cells). In conclusion, thalamic relay neurons present opioid receptors negatively coupled to both HVA and LVA Ca 2+ channels. The presence of two inhibitory effects of DADLE on the total HVA Ca 2+ channels has been observed, and they are distinguishable on the basis of their sensitivity to voltage. It is suggested that Ca 2+ current modulation may play a role in the production and tuning of the rhythmic burst discharge in these neurons.

Cholecystokinin depolarizes rat thalamic reticular neurons by suppressing a K+ conductance.

1. The thalamic reticular nucleus (nRt) is innervated by cholecystokinin (CCK)-containing neurons and contains CCK binding sites. We used tight-seal, whole cell recording techniques with in vitro rat thalamic slices to investigate the action of CCK on neurons in nRt and ventrobasal thalamus (VB). 2. Brief applications of the CCK agonist cholecystokinin octapeptide (26-33) sulfated (CCK8S) evoked prolonged spike discharges in nRt neurons but had no direct effects on VB neuron activity. This selective excitatory action of CCK8S in nRt resulted from a long-lasting membrane depolarization (2-10 min) associated with an increased input resistance. Voltage-clamp recordings revealed that CCK8S reduced membrane conductance by 0.6-3.8 nS, which amounted to 5-54% of the resting conductance of these neurons. 3. The conductance blocked by CCK8S was linear over the range of -50 to -100 mV and reversed near the potassium equilibrium potential. Modifications of extracellular K+ concentration altered the reversal potential of the conductance as predicted by the Nernst equation. The K+ channel blocker Cs+, applied either intracellularly or combined intra- and extracellularly, blocked the response to CCK8S. 4. The CCK8S-induced depolarization persisted after suppression of synaptic transmission by either tetrodotoxin or a low-Ca2+, high-Mg2+ extracellular solution, indicating that the depolarization was primarily due to activation of postsynaptic CCK receptors and not mediated through the release of other neurotransmitters. 5. The selective CCKA antagonists L364,718 and Cam-1481 attenuated the CCK8S-induced depolarization, whereas the CCKB antagonist L365,260 had little or no effect on the depolarization. 6. Our findings indicate that CCK8S, acting via CCKA-type receptors, reduces a K+ leak current, resulting in a long-lasting membrane depolarization that can presumably modify the firing mode of nRt neurons. Through this effect, CCK actions in nRt may strongly influence thalamocortical function.

Modulation of sensory neurone excitatory and inhibitory responses in the ventrobasal thalamus by activation of metabotropic excitatory amino acid receptors

Several different types of metabotropic excitatory amino acid receptors (mGluRs) are present in the thalamus. We have previously shown that the agonists L-AP4 and CCG-I can have apparently presynaptic effects on GABAergic inhibitory transmission in the thalamus. In this study we attempted to characterize the different receptor types which may mediate these effects and the known post-synaptic excitatory actions of 1 S,3 R-ACPD in the ventrobasal thalamus, by using a number of agonists with different spectra of activity at the various mGluRs. Inhibitory responses in ventrobasal thalamic neurones of urethane-anaesthetized rats were evoked by air-jet stimuli to the vibrissae and extracellular recording methods were used to reveal inhibitory responses as an inhibition of excitatory responses in a condition-test paradigm. The Group II and Group III mGluR agonists L-AP4, CCG-I, DCG-IV, 1 S,3 R-ACPD and S-4C3HPG, applied in the vicinity of the recording site by iontophoresis, were found to reduce inhibitions revealed by the condition-test paradigm (by 67, 75, 50, 43 and 77% from control inhibitions, respectively). The endogenous mGluR agonist l-serine- O-phosphate (L-SOP) was found to have similar, although weaker, actions (31% reduction of inhibition), while the Group I agonist 3,5-DHPG had little effect in this test (9% reduction of inhibition). In contrast, both 3,5-DHPG and 1 S,3 R-ACPD had direct excitatory actions on VB neurones, and these could be antagonized by 4CPG. The effects of CCG-I in the condition-test paradigm could be antagonized by the antagonists MCCG, MCPG, but not MAP4. In contrast, we have previously shown that MAP4 was able to block the effects of L-AP4. These data suggest that there may be at least two types of receptor mediating the disinhibitory effects, which may belong to the Group II and Group III type of mGluR, whereas the postsynaptic excitatory responses to mGluR agonists are probably mediated via Group I receptors (possibly mGluR1).

Effect of serotonin depletion on vibrissa-related patterns of thalamic afferents in the rat's somatosensory cortex

To investigate the role of 5-HT in the development of the somatosensory cortex, this amine was depleted in newborn (P-0) rats with a single subcutaneous injection of the toxin 5,7-dihydroxytryptamine (5,7-DHT) and thalamocortical organization was assayed by application of the carbocyanine dye Di-I to the thalamocortical radiations or ventrobasal thalamus, or by staining cortical sections for AChE or cytochrome oxidase (CO). High-performance liquid chromatographic analysis of cortices from animals killed on P-6 or P > 60 demonstrated that 5,7-DHT treatment resulted in 85.04 +/- 12.6% and 72.5 +/- 1.5% reductions in cortical 5-HT, respectively. Alternate cortices from the brains of animals killed on P-6 processed for 5-HT immunoreactivity demonstrated a complete absence of the vibrissa-related pattern of immunoreactivity and only a small number of coarse immunoreactive axons. The 85% depletion of 5-HT did not alter the somatotopic organization of thalamocortical afferents in animals killed on P-6 or P > 60, but it did cause 30.5 +/- 7.3% and 19.1 +/- 3.7% reductions in the cross-sectional areas of the patches of thalamocortical afferents corresponding to the long mystacial vibrissae (p < 0.05). These reductions were not associated with significant reductions in either brain or cortical weight or with decreases in the dimensions of the thalamic representation of the vibrissa follicles. These results indicate that 5-HT plays a significant role in the development of the thalamic innervation of the primary somatosensory cortex.

Thalamic ventrobasal stimulation for pain relief. Probable mechanisms, pathways and neurotransmitters.

Thalamic ventrobasal (VB) stimulation, first performed by Mazars, in 1961, is a valuable means for treating central and deafferentation pain. The way it acts to achieve pain relief, however, is still a matter of controversy. In this paper, the author examines previously proposed hypotheses and suggests that VB stimulation induces pain relief by activation of a multisynaptic inhibitory pathway to the medial thalamus, in which the dopaminergic nigrostriatal system exerts an important role and by modulation of abnormal activity in VB itself. The multisynaptic pathway involved, as well as the neurotransmitters, are suggested: VB stimulation excites somatosensory cortex through the glutaminergic thalamocortical pathway, which in turn, sends excitatory glutaminergic axons to the motor cortex. The sensorymotor cortex originates the excitatory glutaminergic corticostriatal pathway to the anterior putamen. The anterior putamen sends excitatory peptidergic (substance P) pathways to the globus pallidus internus (striatopallidal pathway) and to the substantia nigra reticulata (striatonigral pathway). The globus pallidus internus inhibits the medial thalamus through the pallidothalamic GABAergic pathway. The substantia nigra reticulata sends inhibitory GABAergic projections to the medial thalamus (nigrothalamic pathway) and excites the substantia nigra compacta. The substantia nigra compacta projects excitatory dopaminergic axons to the striatal neurons (nigrostriatal pathway) with output to the globus pallidus internus and substantia nigra reticulata and so on. Data to support this hypothesis are provided by an extensive review of the literature.

Widespread Metabolic Depression and Reduced Somatosensory Circuit Activation Following Traumatic Brain Injury in Rats

The effects of fluid percussion brain injury on the basal metabolic state and responsiveness of a somatosensory circuit to physiologic activation were investigated with [14C]2-deoxyglucose autoradiography. Under controlled physiologic conditions and normothermic brain temperature (37 degrees C), rats were injured with a moderate fluid percussion pulse ranging from 1.7 to 2.1 atm. At 4 or 24 h after traumatic brain injury (TBI), unilateral vibrissae stimulation was carried out, resulting in the metabolic activation of the whisker-barrel circuit. In sham-operated control animals, whisker stimulation resulted in the metabolic activation of the ipsilateral trigeminal medullary complex (177% of control), contralateral ventrobasal thalamus (143% control), and primary somatosensory cortex (153% control). At 4 h after injury, local cerebral metabolic rates of glucose (ICMRglu) were significantly depressed throughout the traumatized hemisphere. Although depressed ICMRglu was most pronounced in cortical regions adjacent to the evolving contusion (53% of control), significant decreases were also seen in more remote areas, including the frontal cortex (75% of control), hippocampus (79% control), and lateral thalamus (68% of control). At 24 h following TBI, ICMRglu remained significantly reduced at the impact site, within the ipsilateral somatosensory cortex and lateral thalamus. Stimulus-evoked increases in ICMRglu were depressed within all three relay stations of the vibrissae-barrel-field circuit at 4 and 24 h after TBI. These results demonstrate both focal and diffuse metabolic depression after moderate TBI. Although the most severe and longer lasting metabolic consequences occurred in cortical and thalamic regions destined to exhibit histopathologic damage, milder abnormalities, most prominent in the early posttraumatic period, were also seen in noninjured areas. The inability to activate the somatosensory circuit metabolically indicates that circuit dysfunction is an acute consequence of TBI. Widespread circuit or synaptic dysfunction would be expected to participate in the functional and behavioral consequences of TBI.

Visual and somatosensory evoked potentials are mediated by excitatory amino acid receptors in the thalamus

In pentobarbital-anaesthetized rats early somatosensory evoked potentials (SEPs) were recorded from the sensory cortex in response to electrical stimulation of the contralateral forepaw and visual evoked potentials (VEPs) from the primary visual cortex in response to single light flashes. Microapplication of the specific non-NMDA antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) into the ventro-basal thalamus (VB) resulted in a pronounced decrease in amplitude and an increase in latency of SEPs, whereas injection of DNQX into the dorsal lateral geniculate nucleus (DGL) induced a pronounced decrease in amplitude and an increase in latency of VEPs. These changes were: (1) dose-dependent (DNQX 0.01–1.0 nmol), (2) receptor-specific, and (3) site-specific. In contrast, the specific NMDA antagonist 2-amino-7-phosphonoheptanoate (AP7; 0.5–5 nmol) did not affect SEPs after microapplication into the VB and less potently reduced the amplitude and increased the latency of VEPs after microapplication into the DGL. The present findings are consistent with the assumption that an excitatory amino acid serves as transmitter at synapses in the rat thalamus mediating the nervous impulses responsible for the generation of SEPs and of VEPs. In addition the results suggest that this transmitter preferentially interacts with non-NMDA receptors.

Pathways involved in thalamic ventrobasal stimulation for pain relief: evidence against the hypothesis VB stimulation -&gt; rostroventral medulla excitation -&gt; dorsal horn inhibition

Despite its use for a long time, the way thalamic ventrobasal (VB) stimulation acts to produce pain relief is still unknown. One of the most accepted hypotheses, sponsored by Tsubokawa among others, proposes that VB stimulation excites raphespinal and reticulospinal neurons of the rostroventral medulla which in turn send respectively inhibitory serotonergic and noradrenergic axons through both dorsolateral funiculi (DLF) to the dorsal horn (DHA) nociceptive neurons; this pathway would be the same as is involved in periventricular-periaqueductal gray (PVG-PAG) stimulation induced inhibition of DH nociceptive neurons. This hypothesis implicates the necessity of DLF intactness; in fact, it was showed that section of bilateral DLF inhibits the response of DH nociceptive neurons to VB stimulation. If the above mentioned hypothesis is correct, one could expect that unilateral VB stimulation would produce bilateral pain relief, VB and PVG stimulation would be useful for treating the same modalities of pain and that in patients with central cord-based pain harboring complete cord transection, VB stimulation would not work at all. In order to check these possibilities, the patients with central cord-based pain admitted to the Division of Neurosurgery, Toronto Hospital between June 1978 and July 1991 to undergo deep brain stimulation (DBS) were reviewed. Sixteen patients were operated on. Based on clinical criteria, four out of these sixteen patients were thought to present complete cord transection (all four were men, with an average age of 48 years and pain secondary to cord injury).(ABSTRACT TRUNCATED AT 250 WORDS)

OFF response transformations in the whisker/barrel system.

1. Previous studies have demonstrated marked differences in the relative sizes of ON and OFF responses of neurons in the whisker/barrel system. In particular, OFF responses are unexpectedly large in thalamic neurons. Extracellular unit recordings were used to examine whether varying the time between stimulus onset and offset differently affects OFF responses of neurons in the trigeminal ganglion, ventrobasal thalamus, and somatosensory cortical layer IV. Controlled whisker stimuli were used to deflect individual vibrissal hairs in different directions. We hypothesized that, in part because of the gradual waning of central inhibition evoked by stimulus onset, OFF responses of thalamic and cortical neurons but not trigeminal ganglion cells would increase in size with longer duration stimuli, with relative changes being greatest in the cortex. 2. OFF response magnitudes for thalamic and cortical neuronal populations increased as the stimulus duration was increased from 200 to 1,400 ms. Increases were greater at nonoptimal deflection angles. Similarly, individual cells having smaller OFF responses for the short-duration stimulus tended to display proportionately greater increases when the stimulus was lengthened. OFF responses of trigeminal ganglion cells were largely unaffected by stimulus duration. 3. Barrel neurons were subclassified as regular-spike units (RSUs) or fast-spike units (FSUs) on the basis of the time course of their action potentials. ON and OFF responses were smaller in the former and, when the stimulus was lengthened, percentage increases in their OFF responses were greater than those in FSUs. Results illustrate nonlinear transformations of the thalamic input signal by RSUs, which are presumed to be excitatory barrel neurons, and extend previous findings of response similarities between thalamocortical units (TCUs) and FSUs, the latter of which are thought to be inhibitory. 4. The time course of OFF response suppression in cortical neurons suggests that stimulus onset evokes central inhibition having two components, a potent one lasting several tens of milliseconds and a weaker one lasting many hundreds of milliseconds. Background activity levels in cortex and thalamus were diminished for > or = 1,800 ms after whisker movement. 5. For TCUs, 200-ms stimuli were less likely than 1,400-ms stimuli to elicit an OFF response, but when responses occurred they consisted of a greater number of spikes timed closer together. By contrast, the 200-ms stimulus OFF responses of the RSUs and FSUs displayed longer interspike intervals than did their 1400-ms responses, with no change in the number of spikes per response.(ABSTRACT TRUNCATED AT 400 WORDS)

Distribution of the postsynaptic dorsal column projection in the cuneate nucleus of monkeys

Cells in the spinal cord that are postsynaptic to primary afferent fibers project to the dorsal column nuclei in the postsynaptic dorsal column pathway. The projection of cells in the cervical spinal cord of monkeys to the cuneate nucleus has been reported to avoid pars rotunda of that nucleus, the part that contains the somatotopic representation of the ipsilateral hand. We used the sensitive anterograde tracer Phaseolus vulgaris leucoagglutinin to reexamine this projection. We made multiple iontophoretic injections into the cervical enlargements of three monkeys (two Macaca fascicularis and one Macaca mulatta). Control injections were made in the contralateral dorsal columns of one of these and in the dorsal roots of a fourth animal (M. fascicularis) to test for transport by fibers of passage. After 28-39 days, the animals were deeply anesthetized and perfused, and the tissue was processed for immunohistochemical detection of the label. In all cases (excluding control injections), labeled fibers and varicosities were distributed widely in the ipsilateral cuneate and external cuneate nuclei, including pars rotunda. The dorsal column nuclei ipsilateral to control injections contained no label or only very few poorly labeled fibers, indicating that labeling through fibers of passage did not contribute importantly to the results. This study indicates that the postsynaptic projection to the cuneate nucleus is widespread and includes pars rotunda. Such projections may contribute to transmission of information originating in nociceptors through the dorsal column-medial lemniscal system to the ventrobasal thalamus.

Release of the nitric oxide precursor, arginine, from the thalamus upon sensory afferent stimulation, and its effect on thalamic neurons in vivo

The nenrophysiology and neuroanatomy of the thalamus have been extensively studied in a variety of species and sensory systems. 9 The identity of the neurotransmitter(s) which mediate the excitation from ascending sensory afferents on to thalamic relay neurons is, however, still unclear, although it appears to be a substance which is a ligand for excitatory amino acid receptors, 16,18 as the responses of ventrobasal thalamus neurons to natural stimulation of somatosensory afferents arising from the mustachial vibrissae of the rat are mediated by ionotropic excitatory amino acid receptors, when stimulation is performed using an air-jet directed at the vibrissa receptor field. 16,18 In an effort to determine the transmitter of these sensory afferents, we have attempted to detect the release of amino acids in the ventrobasal thalamus in vivo upon such stimuli. We have thus used a similar natural stimulation protocol, together with push-pull perfusion and recording in the ventrobasal thalamus, and we describe the release of the amino acid, arginine, in this brain area following physiological stimulation of afferents. Furthermore, we show that application of l-arginine on to thalamic relay neurons can facilitate sensory synaptic transmission, possibily via the synthesis of the diffusable messenger, free radical gas, nitric oxide. This may represent a novel, local positivefeedback, modulatory system which could enhance the responsiveness of thalamic neurons to sensory input.

The function of metabotropic excitatory amino acid receptors in synaptic transmission in the thalamus: Studies with novel phenylglycine antagonists

The phenylglycines 3-hydroxyphenylglycine, 4-carboxy-3-hydroxy-phenylglycine (4C3HPG), 4-carboxyphenylglycine (4CPG) and α-methyl-4-carboxyphenylglycine (MCPG) were evaluated as putative selective antagonists of metabotropic glutamate receptors on single neurones of the ventrobasal thalamus of rats, with a view to using these compounds as tools to elucidate synaptic mechanisms in this brain area. The S-isomers of the latter three compounds were found to reduce excitations evoked by iontophoretically applied 1S,3R-ACPD, but not those evoked by ionotropic excitatory amino receptor agonists. When the antagonists were tested against sensory synaptic responses of ventrobasal neurones, it was found that responses evoked by noxious thermal stimulation of the peripheral receptive field were reduced in parallel with responses to 1S,3R-ACPD. In contrast, responses of neurones evoked by non-noxious (air-jet) stimuli were not reduced by the phenylglycine antagonists and 4C3HPG was found to enhance such responses, possibly by a presynaptic action mediated via mGluR 2 receptors. The reductions of nociceptive responses are discussed in the context of antagonism of mGluR 1 receptors, which are known to be numerous in the thalamus and located on post-synaptic dendrites. The involvement of such receptors in the nociceptive responses of thalamic neurones may be of considerable functional significance.

Neurotransmitters in subcortical somatosensory pathways.

Investigations during recent years indicate that many different neuroactive substances are involved in the transmission and modulation of somesthetic information in the central nervous system. This review surveys recent developments within the field of somatosensory neurotransmission, emphasizing immunocytochemical findings. Increasing evidence indicates a widespread role for glutamate as a fast-acting excitatory neurotransmitter at different levels in somatosensory pathways. Several studies have substantiated a role for glutamate as a neurotransmitter in primary afferent neurons and in corticofugal projections, and also indicate a neurotransmitter role for glutamate in ascending somatosensory pathways. Other substances likely to be involved in somatosensory neurotransmission include the neuropeptides. Many different peptides have been detected in primary afferent neurons with unmyelinated or thinly myelinated axons, and are thus likely to be directly involved in primary afferent neurotransmission. Some neurons giving rise to ascending somatosensory pathways, primarily those with cell bodies in the dorsal horn, are also immunoreactive for peptides. Recent investigations have shown that the expression of neuropeptides, both in primary afferent and ascending tract neurons, may change as a result of various kinds of peripheral manipulation. The occurrence of neurotransmitters in intrinsic neurons and neurons providing modulating inputs to somatosensory relay nuclei (the dorsal horn, the lateral cervical nucleus, the dorsal column nuclei and the ventrobasal thalamus) is also reviewed. Neurotransmitters and modulators in such neurons include acetylcholine, monoamines, GABA, glycine, glutamate, and various neuropeptides.

Spontaneous activity and evoked potentials in the caudal trigeminal nucleus, ventrobasal thalamus, and cerebral cortex of rats with neuropathic trigeminal neuralgia

Incomplete compression of the infraorbital nerve in rats leads to spontaneous neuronal activity in the form of bursts in the caudal trigeminal nucleus and to epileptiform activity in the ventrobasal thalamus and cerebral cortex. From the latter, afterdischarges are also recorded.