Effects of neonatal axoplasmic transport attenuation on the response properties of vibrissae-sensitive neurons in the trigeminal principal sensory nucleus of the rat

We have previously shown that attenuation of axoplasmic transport by application of vinblastine to the developing infraorbital nerve (ION) results in a loss of central vibrissae-related patterns that is not accompanied by changes in the receptive field sizes for the V primary afferents innervating the whisker follicles. The present study examines the relationship between the loss of central vibrissae-related patterns and alterations in the response properties of neurons in the V principal sensory nucleus (PrV) of adult rats that sustained application of vinblastine to the ION at birth. Absence of histochemically demonstrable vibrissae-related patterns in PrV resulted in only modest changes in the receptive fields and response properties of vibrissae-sensitive neurons in this nucleus that projected to the contralateral thalamus. Response latencies to electrical activation of the V ganglion were similar in treated and untreated animals. The mean receptive field size was significantly increased from 1.3 &#45 0.7 vibrissae in controls to 1.7 &#45 0.9 vibrissae in vinblastine-treated animals, and the percentage of cells yielding a tonic response to vibrissae deflection was markedly reduced (p < 0.01 for both measures). Phasically responding cells recorded in vinblastine-treated animals showed a significant reduction in the mean number of spikes per stimulus following deflection of the vibrissae in either the preferred or non-preferred direction relative to cells recorded in normal animals (p < 0.05). The present results indicate that disruption of the normal vibrissae-related aggregates of neurons in PrV by application of vinblastine to the ION has limited effects on the functional representation of the vibrissae in this nucleus.     

Corticofugal influences on neurons of the main trigeminal sensory nucleus

The effects of stimulation of the ipsilateral sensomotor cortex were studied on 88 neurons in the region of the main trigeminal sensory nucleus of a cat. The cortex was stimulated via a coaxial electrode by single impulses. Stimulation of the cortex caused the appearance of EPSPs and action potentials in these neurons; a small number of these responses were monosynaptic. The polarity of the impulse applied to the cortex had a significant effect on the magnitude of the latent period of the response and the postsynaptic reaction, which is apparently caused by the stimulation of different types of cortex neurons. Apparently, corticofugal pulsation regulates the level of sensitivity of the trigeminal sensory neurons.A. A. Bogomolets' Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 1, No. 1, pp. 47–53, July–August, 1969.     

Mechanism of inhibitory action of capsaicin on particulate axoplasmic transport in sensory neurons in culture

The inhibitory effect of capsaicin on axoplasmic transport in cultured dorsal root ganglion cells was analyzed by video-enhanced contrast microscopy. Capsaicin inhibited particle transports in a dose-dependent manner, irrespective of the diameter of axons. The effect of capsaicin was reversible at low concentrations. Capsaicin affected both the anterograde and retrograde transport. Large organelles were more sensitive to capsaicin than small ones in the retrograde transport. An experiment using calcium-sensitive dye, Fura 2, indicated that capsaicin raised the intraneuronal free calcium concentration preceding the inhibition of the transport. Electron microscopy revealed that microtubules and neurofilaments are disorganized and disoriented by capsaicin. We reached a conclusion that capsaicin inhibits fast axoplasmic transport of both anterograde and retrograde directions in all types of somatosensory neurons in culture by disorganizing intraaxonal cytoskeletal structures, through the elevated intracellular Ca²⁺ concentration. © 1993 John Wiley & Sons, Inc.     

The contribution of the principal and spinal trigeminal nuclei to the receptive field properties of thalamic VPM neurons in the rat

Primary sensory information from neurons innervating whisker follicles on one side of a rat's face is relayed primarily through two subnuclei of the brainstem trigeminal complex to the contralateral thalamus. The present experiments were undertaken to separate the contribution of the principal trigeminal nucleus (PrV) from that of the spinal trigeminal nucleus (SpV) to whisker evoked responses in the ventral posterior medial (VPM) nucleus in the adult rat thalamus. Extracellular single-unit responses of VPM neurons to controlled stimulation of the contralateral whiskers under urethane anesthesia were quantified in terms of receptive field size, modal latency, response probability and response magnitude. The SpV contribution to VPM cell responses was isolated by making kainic acid lesions of the PrV. The PrV contribution was ascertained by cutting the trigeminothalamic axons arising from SpV just before they cross the midline. After destruction of the PrV, the SpV pathway alone produced large receptive fields (mean: 9.04 whiskers) and long latency (mean: 11.07 ms) responses from VPM neurons. In contrast, PrV input alone (SpV disconnected) generated small receptive fields (mean: 1.06 whiskers) and shorter latency (mean: 6.74 ms) responses. With both pathways intact the average receptive field size was 2.4 whiskers and peak (modal) response latency was 7.33 ms. The responses with both pathways intact were significantly different from either pathway operating in isolation. Response probability and magnitude followed the same trend. We conclude that normal responses of individual VPM neurons represent the integration of input activity transmitted through both PrV and SpV pathways.     

Temperature-sensitive properties of rat suprachiasmatic nucleus neurons

The hypothalamic suprachiasmatic nucleus (SCN) contains a heterogeneous population of neurons, some of which are temperature sensitive in their firing rate activity. Neuronal thermosensitivity may provide cues that synchronize the circadian clock. In addition, through synaptic inhibition on nearby cells, thermosensitive neurons may provide temperature compensation to other SCN neurons, enabling postsynaptic neurons to maintain a constant firing rate despite changes in temperature. To identify mechanisms of neuronal thermosensitivity, whole cell patch recordings monitored resting and transient potentials of SCN neurons in rat hypothalamic tissue slices during changes in temperature. Firing rate temperature sensitivity is not due to thermally dependent changes in the resting membrane potential, action potential threshold, or amplitude of the fast afterhyperpolarizing potential (AHP). The primary mechanism of neuronal thermosensitivity resides in the depolarizing prepotential, which is the slow depolarization that occurs prior to the membrane potential reaching threshold. In thermosensitive neurons, warming increases the prepotential's rate of depolarization, such that threshold is reached sooner. This shortens the interspike interval and increases the firing rate. In some SCN neurons, the slow component of the AHP provides an additional mechanism for thermosensitivity. In these neurons, warming causes the slow AHP to begin at a more depolarized level, and this, in turn, shortens the interspike interval to increase firing rate.     

Effects of estrogens on cholinergic neurons in the rat basal nucleus

Estrogen replacement in postmenopausal women may help prevent or delay development of Alzheimer's disease. Because loss of basal forebrain cholinergic neurons with reductions in choline acetyltransferase (ChAT) concentration are associated with Alzheimer's disease, we investigated the effect of estradiol (E(2)) and J 861, a non-feminizing estrogen, on cholinergic neurons in the basal forebrain. Ovariectomized rats received E(2), J 861 or vehicle, and basal forebrain sections through the substantia innominata, medial septum, and nucleus of the diagonal band were immunostained for ChAT. ChAT-immunoreactive cells in the basal forebrain were significantly reduced in the ovariectomized rats compared to intact rats, but those ovariectomized rats receiving estrogen replacement with E(2) and J 861 had near normal levels of ChAT-positive neurons. While retrograde tracing experiments with fluorogold injected into the prefrontal cortex showed no significant differences in the number of fluorogold-labeled cells among the groups, ChAT-immunoreactive cells and double-labeled cells were significantly lower in OVX rats than in intact and E(2) rats. Some substantia innominata cells in the J 861 rats were ChAT/estrogen receptor alpha-positive. These results suggest that E(2) and J 861 have positive effects on cholinergic neurons that project from the basal nucleus to the forebrain cortex.     

Effects of low concentrations of tetradotoxin on rat trigeminal ganglion neurons

Voltage clamping and intracellular perfusion methods were used to investigate ionic currents produced by depolarizing shifts of –120 mV from holding potential during experiments on neurons isolated from the trigeminial ganglion of one-month-old rats. It was found that tetradotoxin at low (external) concentrations of 10^–12–10¹⁰ M produced an increase in the amplitude and alternations in the kinetics of inward ionic currents. Similar effects were observed in 8 test cells out of 29. The extent to which the increase in the amplitude of inward ionic currents depended on concentration level could be described by Langmuir's isotherm, with a dissociation constant of the order of 5·10^–12 M. No such tetrodotoxin effects were observed when chloride ions were replaced by a non-penetrating anion in the intracellular solution. It is suggested that tetrodotoxin-sensitive channels exist in the neuronal membrane of the rat trigeminal ganglion, letting through chloride ions during depolarization of the membrane.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 18, No. 6, pp. 723–729, November–December, 1986.     

Response properties of periodontal mechanosensitive neurons in the trigeminal spinal tract nucleus of the cat.

Periodontal mechanosensitive (PM) units were recorded from the trigeminal spinal tract nucleus (Vst) of the cat. The Vst is divided into three subnuclei: oralis (Vo), interpolaris (Vi), and caudalis (Vc). The receptive fields of PM units in Vo and Vi were arranged in a dorsoventral sequence in the mandibular to maxillary divisions, and those in Vc were arranged in a mediolateral sequence. The majority of Vo units were single-tooth ones, whereas more than half the Vi units and all the Vc ones were multitooth units. The PM units in each subnucleus were predominantly responsive to canine tooth stimulation. Most of the PM units in Vo and Vi gave sustained responses to pressure applied to the tooth, were directionally selective, and were most actively excited by canine tooth stimulation in the caudomedial or rostrolateral direction. Vc units, however, were transient. The threshold intensity for firings by canine tooth stimulation was less than 0.05 N. These findings indicate that only the response properties of PM units in the rostral part of Vst resemble those of the trigeminal main sensory nucleus neurons and primary afferent nerves.     

Response of the spinal trigeminal nucleus neurons to electric stimulation of the rat dura mater

Aseptic inflammation of tissues surrounding large meningeal blood vessels, e.g. the superior sagittal sinus, underlies pathogenesis of migraine. This inflammation develops due to antidromic activation of sensory trigeminal nerve endings and is followed by changes in responses of the spinal nucleus of the trigeminal nerve neurons to electrical stimulation of the superior sagittal sinus. However, characteristics of these reactions are still unclear. In experiments ou urethane-anesthetized rats, responses of 387 neurons of the spinal nucleus of the trigeminal nerve to electrical stimulation of the superior sagittal sinus, were recorded. It was tial discharge with the latency 7 to 19 ms (11.4 +/- 0.17 ms) and a subsequent long-lasting discharge with the latency 20 to 50 ms (34.2 +/- 0.8 ms). It is presumed that the first phase reflects orthodromic activation of prevascular A delta and C-fibers of the trigeminal nerve while the second phase is connected with activation of meningeal C-fibers which have low conduction velocity, and/or with a secondary activation of perivascular sensory endings of trigeminal nerve by releasing algogenic and vasoactive substances. These changes could be used as an indicator of efficacy of some antimigraine substances in animal experiments.     

Electrophysiological properties of neurons of the red nucleus in rat brain slices

In experiments on rat brain slices, we carried out intracellular recording from neurons of the red nucleus (RN). Passive electrical properties of these neurons (input resistance, membrane time constant) were evaluated. We detected voltage-dependent rebound depolarization and time dependent inward rectification when passing hyperpolarizing pulses of current through the cell. Injections of depolarizing currents caused rhythmical firing of the neurons; the frequency of these firings depends upon the strength of injected current. Rhythmical firings were also characterized by rapid frequency adaptation when currents of different frequency were injected. Stimulation of regions of slices presumably corresponding to the decussion of the brachium conjunctivum mainly evoked EPSPs with a "fast" rise time in RN neurons. This suggests activation of synaptic input from the cerebellar nucleus interpositus. Stimulation of this same region sometimes evoked EPSP-IPSP mixtures and "pure" IPSPs in RN neurons.L. A. Orbeli Institute of Physiology, Armenian Academy of Sciences, Erevan. Translated from Neirofiziologiya, Vol. 23, No. 5, pp. 607–616, September–October, 1991.     

Preproenkephalin-like immunoreactive and calcium-binding proteins-like immunoreactive double-labelled neurons in the spinal trigeminal nucleus caudalis of the rat

Immunofluorescence histochemical double-staining for preproenkephalin (PPE) and calbindin-D28k (CB), calretinin (CR) or parvalbumin (PV) were performed in the spinal trigeminal nucleus caudalis (Vc) of the rat. Neuronal cell bodies exhibiting PPE-like immunoreactivity were present in all laminae of the Vc, with a higher concentration in lamina II. Most of the CB-, CR- and PV-like immunoreactive neurons were located in lamina II, and some of them were also found in laminae I and III of the Vc. Some PPE-like immunoreactive neurons also showed CB-, CR-, or PV-like immunoreactivities. CB/PPE, CR/PPE and PV/PPE double-labelled neurons were mainly observed in lamina II. The percentages of CB/PPE double-labelled neurons in the total numbers of the CB- and PPE-like immunoreactive neurons were 3.5–1.5% and 3.3–15.7%, respectively. Of all CR- and PPE-like immunoreactive neurons, 4.7–13.5% and 3.7–14.2% showed both CR- and PPE-like immunoreactivities. The ratios of PV/PPE double-labelled neurons in all PV- and PPE-like immunoreactive neurons were 9.7–28.1% and 2.1–8.7%, respectively. The present results indicate that some enkephalinergic neurons in the Vc of the rat also contain calcium-binding proteins.     

Fine structural characteristics and synaptic connections of trigeminocerebellar projection neurons in rat trigeminal nucleus oralis

In order to classify the presynaptic terminals contacting trigeminocerebellar projection neurons (TCPNs) in rat trigeminal nucleus oralis (Vo), electron-microscopic examination of sequential thin sections made from TCPNs located in the border zone (BZ) of Vo, labeled by the retrograde transport of horseradish peroxidase, was undertaken. The use of BZ TCPNs, labeled in Golgi-like fashion so that many of their dendrites and axons were visible, allowed for the determination of the distribution of each bouton type along the soma and dendrites, as well as for the characterization of the morphology and synaptic relations of the labeled axon and its terminals. Three types of axon terminals contacting labeled BZ TCPNs have been recognized, depending upon whether they contain primarily spherical-shaped, agranular synaptic vesicles (S endings); predominantly flattened, agranular synaptic vesicles (F endings); or a population of pleomorphic-shaped, agranular synaptic vesicles (P endings). The S endings represent the majority of axon terminals contacting labeled BZ TCPNs and establish asymmetrical axosomatic and axodendritic synaptic contacts. Many S endings are situated in one of two types of synaptic glomeruli. One type of glomerulus has a large S ending at its core, whereas the other contains a small S ending. Large-S-ending glomeruli include only labeled distal dendrites of BZ TCPNs; small-S-ending glomeruli contain either a labeled soma, proximal dendrite, or distal dendritic shaft. The remaining S endings are extraglomerular, synapsing on distal dendrites. P endings are less frequently encountered and establish intermediate axosomatic and axodendritic synapses. These endings exhibit a generalized distribution along the entire somatodendritic tree. F endings make symmetrical axodendritic synapses with distal dendrites, are only found in glomeruli containing small S endings, and are the least frequently observed ending contacting labeled BZ TCPNs. The majority of axonal endings synapsing on labeled BZ TCPNs are located along distal dendrites, with only a relatively few synapsing terminals situated on proximal dendrites and somata. The axons of labeled BZ TCPNs arise from the cell body and generally give rise to a single short collateral near their points of origin. This collateral remains unbranched and generates several boutons within BZ, while the parent axon acquires a myelin sheath and, without branching further, travels dorsolaterally toward the inferior cerebellar peduncle. The collateral boutons resemble extraglomerular S endings. They contain agranular, spherical-shaped synaptic vesicles and make asymmetrical axodendritic synapses with small-diameter unlabeled dendritic shafts in the BZ neuropil.     

The somatotopy of the masticatory neurons in the rat trigeminal motor nucleus as revealed by HRP study

Young adult albino rats of Wistar strain were used for the present study. 0.5 to 15 microliters of 20-50% of horseradish peroxidase (HRP) were injected into each individual muscle of mastication to label neurons in the trigeminal motor nucleus (TMON) for light microscopic study. The results reveal that: (1) Many HRP-labeled, multipolar neurons are observed in the motor nucleus in each jaw-closing muscle (JCM) with less in each the jaw-opening muscle (JOM). (2) The motor neurons innervating each masticatory muscle in the motor nucleus show a somatotopic arrangement: (a) those innervating the temporalis muscle are located in the medial and dorsomedial parts; (b) those innervating the masseter muscle are located in the intermediate and lateral; (c) those innervating the medial and lateral pterygoid muscles are located in the lateral, ventrolateral and ventromedial parts, respectively; and (d) those innervating the mylohyoid and the anterior belly of the digastric muscles are located in the most ventromedial part of the caudal one-third of the nucleus. Axons of most masticatory motor neurons run ventrolaterally in between the motor and the chief sensory nuclei of the trigeminal nerve. However, those of the mylohyoid and anterior belly of the digastric muscles ascend dorsally to the dorsal aspect of the caudal nucleus and then turn ventrolaterally to join the motor root of the trigeminal nerve. Furthermore, the dendrites of the motor neuron of JCM converge dorsocaudally to the supratrigeminal region. The diameters of neurons of each JCM display a bimodal distribution. However, an unimodal distribution is present in the motor neurons from each JCM. It is suggested that the motor nucleus innervating the JCM is comprised of comprised of alpha- and gamma-motor neurons. It, thus, may provide a neural basis for the regulation of the muscle tone and biting force.     

Effects and consequences of nerve injury on the electrical properties of sensory neurons

Nociceptive pain alerts the body to potential or actual tissue damage. By contrast, neuropathic or "noninflammatory" pain, which results from injury to the nervous system, serves no useful purpose. It typically continues for years after the original injury has healed. Sciatic nerve lesions can invoke chronic neuropathic pain that is accompanied by persistent, spontaneous activity in primary afferent fibers. This activity, which reflects changes in the properties and functional expression of Na+, K+, and Ca2+ channels, initiates a further increase in the excitability of second-order sensory neurons in the dorsal horn. This change persists for many weeks. The source of origin of the pain thus moves from the peripheral to the central nervous system. We hypothesize that this centralization of pain involves the inappropriate release of peptidergic neuromodulators from primary afferent fibers. Peptides such as substance P, neuropeptide Y (NPY), calcitonin-gene-related peptide (CGRP), and brain-derived neurotrophic factor (BDNF) may promote enduring changes in excitability as a consequence of neurotrophic actions on ion channel expression in the dorsal horn. Findings that form the basis of this hypothesis are reviewed. Study of the neurotrophic control of ion channel expression by spinal peptides may thus provide new insights into the etiology of neuropathic pain.