Principal Sensory Nucleus Research Articles

Stable synchronized high-frequency signals from the main sensory and spinal nuclei of the pig activated by Aβ fibers of the maxillary nerve innervating the snout

The primary somatosensory cortex of various species including man, monkey, pig and rat is capable of producing high-frequency signals in the 600 Hz range and above with very little latency jitter. We have recently observed such cortical signals for the trigeminal system of the swine. This study determined the projection of the maxillary nerve innervating the snout to the sensory trigeminal nuclear complex in the brain stem and stability of outputs of each nucleus receiving the projection. The snout stimulation activated large-caliber Aβ fibers in the trigeminal nerve with a mean velocity of 64.4±2.7 m/s (mean±1 S.E.M., six animals) comparable in velocity to the tooth pulp Aβ fibers (57.9±3.4 m/s) obtained from the same animals. These afferents activated the main sensory nucleus, and subnuclei oralis, interpolaris and caudalis of the spinal nucleus, as judged by evoked field potential maps superimposed on the histological maps of the trigeminal nuclei from the same animals. Inputs from these fast afferents arrived at all the four trigeminal nuclei almost simultaneously within a span of 0.7±0.2 ms (mean±1 S.D., seven animals). Evoked high-frequency signals were reproducible with a latency jitter of less than 0.2 ms during the first 4 ms of postsynaptic activity for each of main sensory and spinal nuclei. These results indicate that the snout stimulation activates fast-conducting peripheral afferents which project to all the sensory trigeminal nuclei and produces highly reproducible initial responses nearly simultaneously across the multiple trigeminal nuclei. These outputs from the trigeminal nuclei may play an important role in triggering the stable high-frequency signals in the cortex.

The difference of osteocalcin-immunoreactive neurons in the rat dorsal root and trigeminal ganglia: co-expression with nociceptive transducers and central projection

The co-expression of osteocalcin (OC) with the capsaicin receptor (VR1) and vanilloid receptor 1-like receptor (VRL-1) was examined in the dorsal root (DRG) and trigeminal ganglia (TG). Virtually all OC-immunoreactive (ir) DRG neurons were devoid of VR1- and VRL-1-immunoreactivity (ir). In the TG, 14.1% of OC-ir neurons were also immunoreactive for VR1. Only 1.7% of OC-ir TG neurons co-expressed VRL-1-ir. The distribution of OC-ir was also examined in the spinal cord and trigeminal sensory nuclei. In the spinal cord, the superficial laminae of the dorsal horn were devoid of OC-ir. The neuropil was weakly stained in other regions of the spinal horns. The medullary dorsal horn (MDH) contained numerous OC-ir varicose fibers in laminae I and II. These fibers were occasionally observed originating from the spinal trigeminal tract. The neuropil was weakly stained in deeper laminae of the MDH, and the rostral parts of the trigeminal sensory nuclei. The present study suggests that OC-ir TG nociceptors send their unmyelinated axons to the superficial laminae of the MDH.

Effects of dopamine receptor blockade on cerebral blood flow response to somatosensory stimulation in the unanesthetized rat.

Local cerebral blood flow (CBF) was determined in 30 cerebral structures, including four structures of the whisker-to-barrel cortex sensory pathway, by the quantitative autoradiographic [(14)C]iodoantipyrine method during unilateral vibrissal stimulation in rats administered 0.1 or 1.0 mg/kg haloperidol or its control vehicle intravenously. The low dose of haloperidol had no significant effects on resting CBF or its enhancement by vibrissal stimulation. By standard t tests, the high dose statistically significantly lowered baseline CBF in frontal and visual cortex, hippocampus, dentate gyrus, inferior olive, cerebellar cortex, and the ventral posteromedial (VPM) thalamic nucleus on the unstimulated side, and raised baseline CBF in the lateral habenula; however, these changes lost statistical significance after Bonferroni correction for multiple comparisons. Neither dose had any effects on the increases in CBF evoked by vibrissal stimulation in the principal sensory trigeminal nucleus and barrel cortex, but the higher dose statistically significantly enhanced the percent increases in CBF due to the sensory stimulation in the spinal trigeminal nucleus and VPM thalamic nucleus. These results do not support a role for direct dopaminergic vasoactive mechanisms in the increases in CBF associated with neuronal functional activation.

Pituitary adenylate cyclase-activating peptide in the rat central nervous system: an immunohistochemical and in situ hybridization study.

In the present study the localization of pituitary adenylate cyclase-activating peptide (PACAP)-expressing cell bodies and PACAP projections were mapped in the adult rat brain and spinal cord by using immunohistochemistry and in situ hybridization histochemistry. A widespread occurrence of PACAP-containing cell bodies was found, with the greatest accumulation in several hypothalamic nuclei and in several brainstem nuclei, especially the habenular nuclei, the pontine nucleus, the lateral parabrachial nucleus (LPB), and the vagal complex. PACAP was also present in cell bodies in the olfactory areas, in neocortical areas, in the hippocampus, in the vestibulo- and cochlear nuclei, in cell bodies of the intermediolateral cell column of the spinal cord and in Purkinje cells of the cerebellum, in the subfornical organ, and in the organum vasculosum of the lamina terminalis. An intense accumulation of PACAP-immunoreactive (-IR) nerve fibers was observed throughout the hypothalamus, in the amydaloid and extended amygdaloid complex, in the anterior and paraventricular thalamic nuclei, in the intergeniculate leaflet, in the pretectum, and in several brainstem nuclei, such as the parabrachial nucleus, the sensory trigeminal nucleus, and the nucleus of the solitary tract. PACAP-IR nerve fibers were also found in the area postrema, the posterior pituitary and the choroid plexus, and the dorsal and ventral horn of the spinal cord. The widespread distribution of PACAP in the brain and spinal cord suggests that PACAP is involved in the control of many autonomic and sensory functions as well as higher cortical processes.

Melatonin receptors in human fetal brain: 2-[(125)I]iodomelatonin binding and MT1 gene expression.

The purpose of this study was to identify sites of action of melatonin in the human fetal brain by in vitro autoradiography and in situ hybridization. Specific, guanosine triphosphate (GTP) sensitive, binding of 2-[(125)I]iodomelatonin was localized to the leptomeninges, cerebellum, thalamus, hypothalamus, and brainstem. In the hypothalalmus, specific binding was present in the suprachiasmatic nuclei (SCN) as well as the arcuate, ventromedial and mammillary nuclei. In the brainstem specific binding was present in the cranial nerve nuclei including the oculomotor nuclei, the trochlear nuclei, the motor and sensory trigeminal nuclei, the facial nuclei, and the cochlear nuclei. The localization of MT1 receptor subtype gene expression as determined by in situ hybridization matched the localization of 2-[(125)I]iodomelatonin binding. No MT2 receptor subtype gene expression was detected using this technique. Thus, melatonin may act on the human fetus via the MT1 receptor subtype at a number of discrete brain sites. A major site of action of melatonin in both fetal and adult mammals is the pars tuberalis of the pituitary gland. However, no 2-[(125)I]iodomelatonin binding or melatonin receptor gene expression was detected in the pituitary gland in the present study, indicating that the pituitary, particularly the pars tuberalis, is not a site of action of melatonin in the human fetus.

Convergence of selected inputs from sensory afferents to trigeminal premotor neurons with possible projections to masseter motoneurons in the rabbit

Peripheral input convergence on trigeminal premotor neurons in the vicinity of trigeminal motor nucleus has been investigated. Thirty neurons were identified by their antidromic responses to microstimulation of the masseteric subnucleus of trigeminal motor nucleus (NVmot-mass). Peripheral receptive fields were found in the buccal mucosae, periodontal ligaments, palate, tongue and vibrissae for 16 neurons located in the intertrigeminal area (NVint), supratrigeminal area (NVs), main sensory trigeminal nucleus (NVsnpr) and subnucleus γ of the oral nucleus of the spinal trigeminal tract (NVspo-γ). Eleven neurons in the NVint, NVs and NVspo-γ responded to passive jaw opening: nine neurons were activated and two were inhibited. None of the neurons responded to both the orofacial mechanical stimulation and passive jaw opening. Forty-six percent of neurons (13 out of 28 tested) received inputs from the inferior alveolar nerve (IAN) and 53% of neurons (8 out of 15 tested) received inputs from the infraorbital nerve (ION). Out of 15 neurons tested for inputs from the IAN and ION, 7 neurons in the NVsnpr and NVspo-γ received input from both. Sixteen percent of neurons (4 out of 25) received inputs from the masseteric nerve (MassN). None of the neurons with inputs from IAN and/or ION also received inputs from the MassN. We suggest that trigeminal premotor interneurons with projections to the NVmot-mass fall into two broad categories, those with inputs from the IAN and/or ION and those with inputs from the MassN, possibly muscle spindle afferents, and no neuron receiving inputs from both.

Mechanisms of bicuculline‐induced hypersensitivity of medullary dorsal horn neurons in rats

AbstractThe purpose of the present study was to examine the responses of medullary dorsal horn neurons to microiontophoretic application of the γ‐aminobutyric acid (GABA)A receptor antagonist, bicuculline. The mechanisms of bicuculline‐induced hypersensitivity were also investigated. Extracellular recordings were made with the central barrel of a seven‐barrel micropipette. Microiontophoretic application of bicuculline greatly increased N‐methyl‐D‐aspartic acid (NMDA)‐evoked responses of medullary dorsal horn neurons. Bicuculline also increased the responses to both noxious pinching and brushing of cutaneous receptor fields. Both NMDA and non‐NMDA receptor antagonists blocked the facilitated responses to iontophoretic application of bicuculline. However, the mu and delta receptor agonists did not block the hypersensitivity produced by iontophoretic application of bicuculline. These results suggest that GABA modulates the synaptic transmission of both noxious and non‐noxious information in the trigeminal spinal sensory nuclei. Bicuculline‐induced hypersensitivity seems to be mediated by excitatory amino acid receptors and provides a mechanism for neuropathic pain.

L-type calcium channel-mediated plateau potentials in barrelette cells during structural plasticity.

Development and maintenance of whisker-specific patterns along the rodent trigeminal pathway depends on an intact sensory periphery during the sensitive/critical period in development. Barrelette cells of the brain stem trigeminal nuclei are the first set of neurons to develop whisker-specific patterns. Those in the principal sensory nucleus (PrV) relay these patterns to the ventrobasal thalamus, and consequently, to the somatosensory cortex. Thus PrV barrelette cells are among the first group of central neurons susceptible to the effects of peripheral damage. Previously we showed that membrane properties of barrelette cells are distinct as early as postnatal day 1 (PND 1) and remain unchanged following peripheral denervation in newborn rat pups (Lo and Erzurumlu 2001). In the present study, we investigated the changes in synaptic transmission. In barrelette cells of normal PND 1 rats, weak stimulation of the trigeminal tract (TrV) that was subthreshold for inducing Na(+) spikes evoked an excitatory postsynaptic potential-inhibitory postsynaptic potential (EPSP-IPSP) sequence that was similar to the responses seen in older rats (Lo et al. 1999). Infraorbital nerve transection at birth did not alter excitatory and inhibitory synaptic connections of the barrelette cells. These observations suggested that local neuronal circuits are already established in PrV at birth and remain intact after deafferentation. Strong stimulation of the TrV induced a sustained depolarization (plateau potential) in denervated but not in normal barrelette neurons. The plateau potential was distinct from the EPSP-IPSP sequence by 1) a sustained (>80 ms) depolarization above -40 mV; 2) a slow decline slope (<0.1 mV/ms); 3) partially or totally inactivated Na(+) spikes on the plateau; and 4) a termination by a steep decay (>1 mV/ms) to a hyperpolarizing membrane level. The plateau potential was mediated by L-type Ca(2+) channels and triggered by a N-methyl-D-aspartate (NMDA) receptor-mediated EPSP. gamma-aminobutyric acid-A (GABA(A)) receptor-mediated IPSP dynamically regulated the latency and duration of the plateau potential. These results indicate that after neonatal peripheral damage, central trigeminal inputs cause a large and long-lasting Ca(2+) influx through L-type Ca(2+) channels in barrelette neurons. Increased Ca(2+) entry may play a key role in injury-induced structural remodeling, and/or transsynaptic cell death.

Induction of Heat Shock Protein 70 after Experimental Pulpal Exposure in Rats

Background: Inducible heat shock protein 70s (iHSP70) are expressed by stressful stimuli that result in protein denaturation, and are thought to assist in the maintenance of cellular integrity and viability. In addition, iHSP70 is known to be a sensitive marker of neuronal injury. To my best knowledge, no previous studies have been documented on iHSP70 induction by nociceptive impulse transmission through peripheral nerves not by direct neural damage. The purpose of this study was to examine the hypothesis that iHSP70 can be expressed in the nervous system, which is related to the dental nociceptive pathway, by tooth pulp inflammation. Methods: The pulp of rat mandibular molars was exposed. Animals were sacrificed at 1, 4, and 7 days after pulpal exposure, and the pulps were evaluated histologically. Also, iHSP70 levels were examined in the Gasserian ganglion (GG) and the trigeminal sensory nucleus (TSN). Results: At 4 days after pulpal exposure, iHSP70 was significantly more expressed in the ipsilateral GG than in the contralateral GG. In the histological study, inflammation was found in the entire pulp tissue at 4 days. There were no significant differences in iHSP70 levels between the ipsilateral TSN and the contralateral TSN. Also, there were no significant differences in iHSP70 expression of GG and TSN between both sides at 1 and 7 days after pulpal exposure. Conclusions: These results suggest that iHSP70 can be expressed in the GG at 4 days after pulpal exposure by nociceptive impulses due to pulpal inflammation

Chemoanatomical separation of vibrissal trigeminal primary afferents in the rat: a special central representation of supraorbital vibrissae

A choleratoxin B subunit transganglionic labelling technique and NPY immunohistochemistry were applied in the rat to achieve the chemoanatomical separation of myelinated vibrissal primary afferents, previously considered to be morphologically indistinguishable. Further, a special central representation pattern of supraorbital vibrissae was observed in the trigeminal brainstem nuclear complex: (1) Choleratoxin-labelled supraorbital vibrissal primary afferents terminated densely in their appropriate barrelettes in the trigeminal principal sensory nucleus, in the spinal oral subnucleus, in the caudal part of the spinal interpolar subnucleus, and in lamina IV of the caudal part of the spinal caudal subnucleus. (2) A second population of choleratoxin-labelled vibrissal afferents was also observed, terminating only in lamina III of the caudal subnucleus. (3) After peripheral nerve transection, NPY-immunoreactive supraorbital vibrissal primary afferent fibres appeared in their appropriate barrelettes in the principal sensory nucleus and the caudal part of the interpolar subnucleus, while in the caudal part of the caudal subnucleus NPY-immunoreactive vibrissal primary afferent terminals were found exclusively in the inner part of lamina II, extending over the outer part of lamina III. NPY-immunoreactive supraorbital vibrissal primary afferents were never found in the oral subnucleus. In contrast with the rules of the central representation of the mystacial (infraorbital) vibrissae, the multiple representation of the supraorbital vibrissae in the caudal subnucleus and the dense, barrelette-like terminal arborization of the choleratoxin-labelled supraorbital vibrissal primary afferents in the oral subnucleus apparently indicate an enhanced role of supraorbital vibrissae in reflexes that protect the eyes and the head from damage.

Immunohistochemical study on the distribution of ion channels in rat trigeminal sensory nucleus

삼차신경절의 뉴론이 구강악안면영역에서의 촉각, 압각, 온도각 및 통각 등 다양한 감각을 중추신경계로 전달하는 역 할을 하는 것은 주지의 사실이다. 이러한 신경전달에 있어서 이온통로는 감각정보를 전달하는데 핵심적인 역할을 수행 한다. 이 중 소디움 통로는 활동전위의 발생에 중요하며, 칼슘 통로는 시냅스 전도에 있어서 필수적인 역할을 수행하고, 포타슘 통로는 안정막전압의 유지 및 재분극에 관여한다. 최근에 여러 가지의 이온통로들의 뇌조직내의 분포에 관한 연 구가 시작되고 있는데 삼차신경의 일차구심뉴론이 종지하는 삼차신경핵 즉 삼차신경 척수감각핵, 삼차신경 주감각핵, 삼차신경 중뇌핵 및 삼차신경 운동핵에 존재하는 이온통로에 관한 연구는 매우 희소하여 본 연구에서는 흰쥐의 삼차신 경핵에 존재하는 소디움, 칼슘 및 포타슘 이온통로들을 면역조직화학적 방법으로 조사하여 다음과 같은 결과를 얻었다. (1) 소디움 통로는 삼차신경 척수감각핵, 삼차신경 주감각핵 및 삼차신경 운동핵 모두에서 강하게 염색되었다. (2) 칼슘 통로는 삼차신경 척수감각핵에서는 N-type 통로가 중등도로 염색되었으며, P/Q-type 통로는 약하게 염색 되었으나R-type 통로는거의염색되지않았다. 삼차신경주감각핵에서는P/Q-type 통로가매우약하게염색되었다. (3) 포타슘 통로는 삼차신경 척수감각핵과 삼차신경 주감각핵에서 inwardly rectifying 포타슘 통로(Kir 2.1)가 중등 도로 염색되었고, voltage-gated 포타슘 통로(Kv 4.2)가 약하게 염색되었으며, BKCa는 그 염색 정도가 매우 약 하게 나타났다. 이상의 결과를 종합해 볼 때 삼차신경 감각핵에는 소디움 통로의 분포가 가장 많았으며, 칼슘통로에서는 N-type이, 포타슘 통로 중에는 inwardly rectifying 통로(Kir 2.1)가 가장 많이 분포함을 관찰할 수 있었다.

Topographical localization of glial cell line-derived neurotrophic factor in the human brain stem: an immunohistochemical study of prenatal, neonatal and adult brains

As a step towards the identification of the neuronal populations responsive to glial cell line-derived neurotrophic factor (GDNF) in the human nervous system and their changes with age, this study reports on the immunohistochemical localization of the protein GDNF in the autoptic normal human brain stem of pre- and full-term newborns and adult subjects. Two different anti-GDNF polyclonal antibodies were used. Western blot analysis on homogenates of human and rat brain and recombinant human GDNF resulted in differential detection of monomeric and dimeric forms of the proteins. The ABC immunohistochemical technique on cryostat tissue sections showed an uneven distribution of GDNF-like immunoreactive nerve fibers and terminals and neuronal cell bodies. Immunoreactive elements were mainly localized to the spinal trigeminal, cuneate, solitary, vestibular, and cochlear sensory nuclei, dorsal motor nucleus of the vagus nerve, ventral grey column, hypoglossal nucleus, dorsal and ventrolateral medullary reticular formation, pontine subventricular grey and locus coeruleus, lateral regions of the rostral pontine tegmentum, tectal plate, trochlear nucleus, dorsal and median raphe nuclei, caudal and rostral linear nuclei, cuneiform nucleus, and substantia nigra. Comparison between pre- and full-term newborns and adult subjects revealed changes with age in density of positive innervation and frequency of immunoreactive perikarya. The results obtained provide detailed information on the occurrence of GDNF-like immunoreactive neurons in the human brain stem and suggest that the protein is present in a variety of neuronal systems, which subserve different functional activities, at developmental ages and in adult brains.

Synaptic plasticity in the trigeminal principal nucleus during the period of barrelette formation and consolidation

We examined whether the postsynaptic responses of cells in the principal sensory nucleus of the trigeminal nerve (PrV) are subject to long-term changes in synaptic strength, and if such changes were correlated the whisker-specific patterning during and just after the critical period for pattern formation. We used an in vitro brainstem preparation in which the trigeminal ganglion (TG) and PrV remained attached. By electrically activating TG afferents, we evoked large-amplitude extracellular field potentials. These responses were postsynaptic in origin and blocked by the glutamate antagonist, DNQX. At P1, a time when barrelettes are consolidating, high frequency stimulation of their afferents led to an immediate (<1 min) and long-lasting (≥90 min) reduction (35%) in the amplitude of the evoked response. At P3–7, when the pattern of barrelettes have stabilized, the same form of tetanus led to an immediate and long-lasting increase (40%) in the amplitude of the response. Both forms of synaptic plasticity were mediated by the activation of L-type Ca 2+ channels. Application of the L-type channel blocker, nitrendipine, led to a complete blockade of any the tetanus induced changes. These associative processes may regulate the patterning and maintenance of whisker-specific patterns in the brainstem trigeminal nuclei.

Three-dimensional computerised atlas of the rat brain stem precerebellar system: approaches for mapping, visualization, and comparison of spatial distribution data.

Comparisons of microscopical neuroanatomic data from different experiments and investigators are typically hampered by the use of different section planes and dissimilar techniques for data documentation. We have developed a framework for visualization and comparison of section-based, spatial distribution data, in brain stem nuclei. This framework provides opportunities for harmonized data presentation in neuroinformatics databases. Three-dimensional computerized reconstructions of the rat brain stem and precerebellar nuclei served as a basis for establishing internal coordinate systems for the pontine nuclei and the precerebellar divisions of the sensory trigeminal nuclei. Coordinate based diagrams were used for presentation of experimental data (spatial distribution of labelled neurons and axonal plexuses) from standard angles of view. Each nuclear coordinate system was based on a cuboid bounding box with a defined orientation. The bounding box was size-adjusted to touch cyto- and myeloarchitectonically defined boundaries of the individual nuclei, or easily identifiable nearby landmarks. We exemplify the use of these internal coordinate systems with dual retrograde neural tracing data from pontocerebellar and trigeminocerebellar systems. The new experimental data were combined, in the same coordinate based diagrams, with previously published data made available via a neuroinformatics data repository (www.nesys.uio.no/Database, see also www.cerebellum.org). Three-dimensional atlasing, internal nuclear coordinate systems, and consistent formats for presentation of neuroanatomic data in web-based data repositories, offer new opportunities for efficient analysis and re-analysis of neuroanatomic data.

Osteopontin-immunoreactivity in the rat trigeminal ganglion and trigeminal sensory nuclei

Osteopontin-immunoreactivity (OPN-ir) was examined in the oro-facial tissues and trigeminal sensory nuclei (principal sensory nucleus and spinal trigeminal nucleus) to ascertain the peripheral ending and central projection of OPN-containing primary sensory neurons in the trigeminal ganglion (TG). No staining was observed using mouse monoclonal anti-OPN antibody preabsorbed with recombinant mature OPN. OPN-immunoreactive (ir) peripheral endings were classified into two types: encapsulated and unencapsulated types. Unencapsulated endings were subdivided into two types: simple and complex types. Simple endings were characterized by the thin neurite that was usually devoid of ramification. These endings were seen in the hard plate and gingiva. The complex type was characterized by the thick ramified neurite, and observed in the vibrissa, hard palate, and molar periodontal ligament. Encapsulated endings were found only in the hard palate. The trigeminal sensory nuclei contained OPN-ir cell bodies and neuropil. The neuropil was devoid of ir in laminae I and II of the medullary dorsal horn (MDH), and had various staining intensities in other regions of the trigeminal sensory nuclei. Transection of the infraorbital and inferior alveolar nerves caused an increase of OPN-ir intensity in ipsilateral TG neurons. The staining intensity of the neuropil also increased in the trigeminal sensory nuclei ipsilateral to the neurotomy excepting laminae I and II of the MDH. The present study indicates that OPN-ir primary sensory neurons in the TG innervate encapsulated and unencapsulated corpuscular endings. Such neurons probably project their central terminals to the trigeminal sensory nuclei except for the superficial laminae of the MDH.

Reticular premotor neurons projecting to both facial and hypoglossal nuclei receive trigeminal afferents in rats

The distribution of premotor neurons projecting to motor nuclei of both the VIIth (VII) and XIIth (XII) nerves was examined in the pontomedullary reticular formation (RF) of the rat by using retrograde double labeling. After injection of two different tracers in the VII and the XII, most of the double labeled neurons were found caudally in the dorsal RF whereas rostrally they were located in the ventral RF. In some experiments, additional injections of an anterograde tracer were made in the sensory trigeminal nuclei. Anterogradely labeled trigeminal boutons were found in contact with retrogradely double labeled neurons throughout the pontomedullary RF. These neurons were mainly encountered ventral to the trigeminal motor nucleus and dorsal to the VII. Functionally, this region is known to be involved in eye protection mechanisms.

Response properties of periodontal mechanosensitive neurones in the rat trigeminal sensory complex projecting to the posteromedial ventral nucleus of the thalamus

Unitary discharges from periodontal mechanosensitive (PM) neurones responding to mechanical stimulation of the tooth were recorded from the trigeminal sensory complex in the rat brainstem. Of the PM units recorded, 22% were activated by antidromic stimulation of the contralateral (20%) or ipsilateral (2%) posteromedial ventral nucleus of the thalamus. Although thalamic-projecting neurones were recorded extensively throughout the trigeminal sensory complex, they originated most often in the region from the caudal main sensory nucleus to the rostral subnucleus oralis of the trigeminal spinal tract nucleus. The response latencies of the rostral nucleus units to orthodromic stimulation of peripheral receptive fields and antidromic stimulation of the thalamus were significantly shorter than those of the caudal nucleus units. More than half were single-tooth units originating from incisor teeth. They responded continuously when pressure was applied to the tooth. The magnitude of the response varied with the direction of the stimulus. Maximal responses were obtained when the stimulus was applied labiolingually or vice versa. The threshold for mechanical stimulation of the tooth was less than 0.05 N. The rostrocaudal distribution and response properties of thalamic-projecting PM neurones were very similar to those of non-thalamic-projecting PM units that were not activated by antidromic stimulation of the thalamus.

Effects of anesthesia on functional activation of cerebral blood flow and metabolism.

Functional brain mapping based on changes in local cerebral blood flow (lCBF) or glucose utilization (lCMR(glc)) induced by functional activation is generally carried out in animals under anesthesia, usually alpha-chloralose because of its lesser effects on cardiovascular, respiratory, and reflex functions. Results of studies on the role of nitric oxide (NO) in the mechanism of functional activation of lCBF have differed in unanesthetized and anesthetized animals. NO synthase inhibition markedly attenuates or eliminates the lCBF responses in anesthetized animals but not in unanesthetized animals. The present study examines in conscious rats and rats anesthetized with alpha-chloralose the effects of vibrissal stimulation on lCMR(glc) and lCBF in the whisker-to-barrel cortex pathway and on the effects of NO synthase inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME) on the magnitude of the responses. Anesthesia markedly reduced the lCBF and lCMR(glc) responses in the ventral posteromedial thalamic nucleus and barrel cortex but not in the spinal and principal trigeminal nuclei. L-NAME did not alter the lCBF responses in any of the structures of the pathway in the unanesthetized rats and also not in the trigeminal nuclei of the anesthetized rats. In the thalamus and sensory cortex of the anesthetized rats, where the lCBF responses to stimulation had already been drastically diminished by the anesthesia, L-NAME treatment resulted in loss of statistically significant activation of lCBF by vibrissal stimulation. These results indicate that NO does not mediate functional activation of lCBF under physiological conditions.

Jaw-muscle spindle afferent pathways to the trigeminal motor nucleus in the rat.

Neural pathways conveying proprioceptive feedback from the jaw muscles were studied in rats by combining retrograde and intracellular neuronal labeling. Initially, horseradish peroxidase was iontophoresed unilaterally into the trigeminal motor nucleus (Vmo). Two days later, 1-5 jaw-muscle spindle afferent axons located in the mesencephalic trigeminal nucleus were physiologically identified and intracellularly stained with biotinamide. Stained mesencephalic trigeminal jaw-muscle spindle afferent axon collaterals and boutons were predominantly distributed in the supratrigeminal region (Vsup), Vmo, dorsomedial trigeminal principal sensory nucleus (Vpdm), parvicellular reticular formation (PCRt), alpha division of the parvicellular reticular formation (PCRtA), and dorsomedial portions of the spinal trigeminal subnuclei oralis (Vodm), and interpolaris (Vidm). Numerous neurons retrogradely labeled with horseradish peroxidase from the trigeminal motor nucleus were found bilaterally in the PCRt, PCRtA, Vodm, and Vidm. Retrogradely labeled neurons were also present contralaterally in the Vsup, Vpdm, Vmo, peritrigeminal zone, and bilaterally in the dorsal medullary reticular field. Putative contacts between intracellularly stained mesencephalic trigeminal jaw-muscle spindle afferent boutons and trigeminal premotor neurons retrogradely labeled with horseradish peroxidase were found in the ipsilateral Vodm, PCRtA, and PCRt, as well as the contralateral Vsup, Vmo, Vodm, PCRt, and PCRtA. Thus, multiple disynaptic jaw-muscle spindle afferent-motoneuron circuits exist. These pathways are likely to convey long-latency jaw-muscle stretch reflexes and may contribute to stiffness regulation of the masticatory muscles.

Deep Brain Stimulation for the Control of Pain

The most common sites of deep brain stimulation (DBS) for relief of pain are the periaqueductal gray (PAG) for nociceptive pain and the principal sensory nucleus of the thalamus (Vc) for control of neuropathic pain. The mechanism of action of PAG stimulation seems to involve release of endogenous opiates, whereas the mechanism of Vc stimulation may involve either antidromic activation of the spinothalamic tract or orthodromic activation of thalamocortical relay cells. Success rates are higher for PAG stimulation than for Vc stimulation, but long-term success rates for both are in the range 40 to 60%. The rate of complications with DBS is lower in recent literature of DBS for movement disorders than in earlier literature of DBS for pain, suggesting that hardware modifications have decreased the rate of complications. DBS is an option in patients with chronic pain who are refractory to other modes of medical and surgical therapy.