Secondary Neurons Research Articles

前半規管から入力を受ける興奮性前庭神経核細胞の中・間脳への軸索投射

The axonal projections of 34 anterior canal (AC)-activated excitatory secondary vestibular neurons to the mesodiencephalon were studied electrophysiologically in cats. AC-related neurons were identified by monosynaptic activation elicited by electrical stimulation of the vestibular nerve and activation following nose-down rotation of the animal's head. Single excitatory neurons were identified by antidromic activation following electrical stimulation of the contralateral medial longitudinal fasciculus and oculomotor nucleus. The axonal projections of the identified neurons were then studied by systematic, antidromic stimulation of the mesodiencephalon. Ten of the 34 AC-related excitatory neurons were antidromically activated from the superior rectus (SR) subdivision of the oculomotor nucleus, central gray, interstitial nucleus of Cajal, dorsomedial part of Forel's field H and ventrobasal complex of the thalamus. In three other AC neurons, antidromic activation was examined only for the INC, but not for the thalamus. In the remaining 21 AC neurons, antidromic activation was obtained from the SR subdivision, but not from more rostral areas. These results suggest that AC-related excitatory neurons give off axon collaterals to the premotor areas to generate vertical eye movements and the thalamus concerning perception of vestibular sensation.

The pineal organ as a folded retina: Immunocytochemical localization of opsins

The most simple pineal complex (the pineal and parapineal organs of lampreys), consists of saccular evaginations of the diencephalic roof, and has a retina-like structure containing photoreceptor cells and secondary neurons. In more differentiated vertebrates, the successive folding of the pineal wall multiplies the cells and reduces the lumen of the organ, but the pattern of the histological organization remains similar to that of lampreys; therefore, we consider the histological structure of the pineal organ of higher vertebrates as a ‘folded retina’. The cell membrane of several pineal photoreceptor outer-segments of vertebrates immunoreact with anti-retinal opsin antibodies supporting the view of retina-like organization of the pineal. Some other pineal outer segments do not react with retinal anti-opsin antibodies, a result suggesting the presence of special pineal photopigments in different types of pinealocytes that obviously developed during evolution. The chicken pinopsin, detected in the last years, may represent one of these unknown photopigments. Using antibodies against chicken pinopsin, we compared the immunoreactivity of different photoreceptors of the pineal organs from cyclostomes to birds at the light and electron microscopic levels. We found pinopsin immunoreaction on all pinealocytes of birds and on the rhodopsin-negative large reptilian pinealocytes. As the pinopsin has an absorption maximum at 470 nm, these avian and reptilian immunoreactive pinealocytes can be regarded as green-blue light-sensitive photoreceptors. Only a weak immunoreaction was observed on the frog and fish pinealocytes and no reaction was seen in cyclostomes and in the frontal organ of reptiles. Some photoreceptors of the retina of various species also reacted the pinopsin antibodies, therefore, pinopsin must have certain sequential similarity to individual retinal opsins of some vertebrates.

The pineal organ as a folded retina: Immunocytochemical localization of opsins*

The most simple pineal complex (the pineal and parapineal organs of lampreys), consists of saccular evaginations of the diencephalic roof, and has a retina‐like structure containing photoreceptor cells and secondary neurons. In more differentiated vertebrates, the successive folding of the pineal wall multiplies the cells and reduces the lumen of the organ, but the pattern of the histological organization remains similar to that of lampreys; therefore, we consider the histological structure of the pineal organ of higher vertebrates as a ‘folded retina’. The cell membrane of several pineal photoreceptor outer‐segments of vertebrates immunoreact with anti‐retinal opsin antibodies supporting the view of retina‐like organization of the pineal. Some other pineal outer segments do not react with retinal anti‐opsin antibodies, a result suggesting the presence of special pineal photopigments in different types of pinealocytes that obviously developed during evolution. The chicken pinopsin, detected in the last years, may represent one of these unknown photopigments. Using antibodies against chicken pinopsin, we compared the immunoreactivity of different photoreceptors of the pineal organs from cyclostomes to birds at the light and electron microscopic levels. We found pinopsin immunoreaction on all pinealocytes of birds and on the rhodopsin‐negative large reptilian pinealocytes. As the pinopsin has an absorption maximum at 470 nm, these avian and reptilian immunoreactive pinealocytes can be regarded as green‐blue light‐sensitive photoreceptors. Only a weak immunoreaction was observed on the frog and fish pinealocytes and no reaction was seen in cyclostomes and in the frontal organ of reptiles. Some photoreceptors of the retina of various species also reacted the pinopsin antibodies, therefore, pinopsin must have certain sequential similarity to individual retinal opsins of some vertebrates.

In vivo stimulation-induced release of manganese in rat amygdala

The role of manganese ions in neural functions is poorly understood because of the low level of manganese in the brain. An excess of this ion is associated with neurological disorders such as extrapyramidal symptoms. We demonstrated that manganese may be taken up by piriform neurons (tertiary olfactory neurons) after release from the terminals of secondary olfactory neurons, in which 54 Mn taken up by the soma may be anterogradely transported [A. Takeda, Y. Kodama, S. Ishiwatari, S. Okada, Manganese transport in the neural circuit of Rat CNS, Brain Res. Bull. (45) (1998) 149–152]. Here we demonstrate for the first time that 54 Mn previously taken up into the amygdala is released with neurotransmitters into the extracellular space during stimulation with high K +. The results suggest that the role of manganese ions in the amygdala, and probably in the olfactory system, is dynamically linked to neural signalling processes.

Actual problems of the cerebrospinal fluid-contacting neurons.

Cerebrospinal fluid (CSF)-contacting neurons form a part of the circumventricular organs of the central nervous system. Represented by different cytologic types and located in different regions, they constitute a CSF-contacting neuronal system, the most central periventricular ring of neurons in the brain organized concentrically according to our concept. Because the central nervous system of deuterostomian echinoderm starfishes and the prochordate lancelet is composed mainly of CSF-contacting-like neurons, we hypothesize that this cell type represents ancient cells, or protoneurons, in the vertebrate brain. Neurons may contact the ventricular CSF via their dendrites, axons, or perikarya. Most of the CSF-contacting nerve cells send their dendritic processes into the ventricular cavity, where they form ciliated terminals. These ciliated endings resemble those of known sensory cells. By means of axons, the CSF-contacting neurons also may contact the external CSF space, where the axons form terminals of neurohormonal type similar to those known in the neurohemal areas. The most simple CSF-contacting neurons of vertebrates are present in the terminal filum, spinal cord, and oblongate medulla. The dendritic pole of these medullospinal CSF-contacting neurons terminates with an enlargement bearing many stereocilia in the central canal. These cells are also supplied with a 9 x 2 + 2 kinocilium that may contact Reissner's fiber, the condensed secretory material of the subcommissural organ. The Reissner's fiber floating freely in the CSF leaves the central canal at the caudal open end of the terminal filum in lower vertebrates, and open communication is thus established between internal CSF and the surrounding tissue spaces. Resembling mechanoreceptors cytologically, the spinal CSF-contacting neurons send their axons to the outer surface of the spinal cord to form neurosecretory-type terminals. They also send collaterals to local neurons and to higher spinal segments. In the hypothalamic part of the diencephalon, neurons of two circumventricular organs, the paraventricular organ and the vascular sac, of the magnocellular neurosecretory nuclei and several parvocellular nuclei, form CSF-contacting dendritic terminals. A CSF-contacting neuronal area also was found in the telencephalon. The CSF-contacting dendrites of all these areas bear solitary 9 x 2 + 0 cilia and resemble chemoreceptors and developing photoreceptors cytologically. In electrophysiological experiments, the neurons of the paraventricular organ are highly sensitive to the composition of the ventricular CSF. The axons of the CSF-contacting neurons of the paraventricular organ and hypothalamic nuclei terminate in hypothalamic synaptic zones, and those of magno- and parvocellular neurosecretory nuclei also form neurohormonal terminals in the median eminence and neurohypophysis. The axons of the CSF-contacting neurons of the vascular sac run in the nervus and tractus sacci vasculosi to the nucleus (ganglion) sacci vasculosi. Some hypothalamic CSF-contacting neurons contain immunoreactive opsin and are candidates to represent the "deep encephalic photoreceptors." In the newt, cells derived from the subependymal layer develop photoreceptor outer segments protruding to the lumen of the infundibular lobe under experimental conditions. Retinal and pineal photoreceptors and some of their secondary neurons possess common cytologic features with CSF-contacting neurons. They contact the retinal photoreceptor space and pineal recess, respectively, both cavities being derived from the third ventricle. In addition to ciliated dendritic terminals, there are intraventricular axons and neuronal perikarya contacting the CSF. Part of the CSF-contacting axons are serotoninergic; their perikarya are situated in the raphe nuclei. Intraventricular axons innervate the CSF-contacting dendrites, intraventricular nerve cells, and/or the ventricular surface of the ependyma. (ABSTRACT TRUNCATED)

Neural Substrates for Species Recognition in the Time-Coding Electrosensory Pathway of Mormyrid Electric Fish

Mormyrid electric fish have species- and sex-typical electric organ discharges (EODs). One class of tuberous electroreceptors, the knollenorgans, plays a critical role in electric communication; one function is species recognition of EOD waveforms. In this paper, we describe cell types in the knollenorgan central pathway, which appear responsible for analysis of the temporal patterns of spikes encoded by the knollenorgans in response to EOD stimuli. Secondary sensory neurons in the nucleus of the electrosensory lateral line lobe (NELL) act as relays of peripheral responses. They fire a single phase-locked spike to an outside positive-going voltage step. Axons from the NELL project to the toral nucleus exterolateralis pars anterior (ELa). Immediately after they enter the ELa, they send collaterals to terminate on one to three ELa large cells and then continue in a lengthy neuronal pathway that traverses the ELa several times. After a path length of up to 5 mm, the NELL axon terminates on as many as 70 ELa small cells. Thus the large cells appear to be excited first, followed by the small cells, with the intervening length of the axon serving as a delay line. The large cells also respond with phase-locked spikes to voltage steps. Large cell axons extend for approximately 1 mm and terminate on several small cells within the ELa. The terminals are known to be GABAergic inputs and are presumed inhibitory. We propose that small cells receive direct inhibition from large cells and delayed excitation from NELL axons. The small cells may act as anti-co-incidence detectors to analyze the temporal structure of the EOD waveform.

Interdependence of spatial properties and projection patterns of medial vestibulospinal tract neurons in the cat.

Activity of vestibular nucleus neurons with axons in the ipsi- or contralateral medial vestibulospinal tract was studied in decerebrate cats during sinusoidal, whole-body rotations in many planes in three-dimensional space. Antidromic activation of axon collaterals distinguished between neurons projecting only to neck segments from those with collaterals to C6 and/or oculomotor nucleus. Secondary neurons were identified by monosynaptic activation after labyrinth stimulation. A three-dimensional maximum activation direction vector (MAD) summarized the spatial properties of 151 of 169 neurons. The majority of secondary neurons (71%) terminated above the C6 segment. Of these, 43% had ascending collaterals to the oculomotor nucleus (VOC neurons), and 57% did not (VC neurons). The majority of VOC and VC neurons projected contralaterally and ipsilaterally, respectively. Most C6-projecting neurons could not be activated from oculomotor nucleus (V-C6 neurons) and projected primarily ipsilaterally. All VO-C6 neurons projected contralaterally. The distributions of MADs for secondary neurons with different projection patterns were different. Most VOC (84%) and contralaterally projecting VC (91%) neurons had MADs close to the activation vector of a semicircular canal pair, compared with 54% of ipsilaterally projecting VC (i-VC) and 39% of V-C6 neurons. Many i-VC (44%) and V-C6 (48%) neurons had responses suggesting convergent input from horizontal and vertical canal pairs. Horizontal and vertical gains were comparable for some, making it difficult to assign a primary canal input. MADs consistent with vertical-vertical canal pair convergence were less common. Type II yaw or type II roll responses were seen for 22% of the i-VC neurons, 68% of the V-C6 neurons, and no VOC cells. VO-C6 neurons had spatial properties between those of VOC and V-C6 neurons. These results suggest that secondary VOC neurons convey semicircular canal pair signals to both ocular and neck motor centers, perhaps linking eye and head movements. Secondary VC and V-C6 neurons carry more processed signals, possibly to drive neck and forelimb reflexes more selectively. Two groups of secondary i-VC neurons exhibited vertical-horizontal canal convergence similar to that present on neck muscles. The vertical-vertical canal convergence present on many neck muscles, however, was not present on medial vestibulospinal neurons. Spatial transformations achieved by the vestibulocollic reflex may occur in part on secondary neurons but further combination of canal signals must take place to generate compensatory muscle activity.

Timing of secondary vestibular neuron responses to a range of rotational head movements.

Secondary vestibular neurons exhibit a wide variety of responses to a head movement, with the response of each secondary neuron depending upon the particular primary afferents converging onto it. A single head movement is thereby registered in a distributed manner. This paper focuses on implications of afferent convergence to the relative timing of secondary neuron response modulation during rotational movements about a combination of horizontal axes. In particular, the neurons of interest are those that receive input from afferents innervating the vertical semicircular canals, and the movements of interest are those that have a sinusoidal component about one vertical canal axis and a sinusoidal component about another, approximately orthogonal, vertical canal axis. Under these conditions, the present research shows that it is possible for two or more secondary neurons to have a different relative timing of response (i.e., different relative phase of the periodic modulation in firing rate) for different head movements, and for the neurons to switch their order of response for different movements. For particular head movements, those same neurons will respond in phase. From the point of view of the nervous system, the relative timing of neuron responses may tell which movement is taking place, but with certain restrictions as discussed in the present paper. Shown here is that, among those head movements for which the two components of rotation may be at any phase relative to one another and have any relative amplitude, an in-phase response of just two neurons cannot identify a single motion. Two neurons that respond in phase for one motion must respond in phase for an entire range of motions; all motions in that range are thus response-equivalent, in the sense that the pair of neurons cannot distinguish between the two motions. On the other hand, an in-phase response of three neurons can identify a single motion, for certain patterns of primary afferent convergence.

Relation between axon morphology in C1 spinal cord and spatial properties of medial vestibulospinal tract neurons in the cat.

Twenty-one secondary medial vestibulospinal tract neurons were recorded intraaxonally in the ventromedial funiculi of the C1 spinal cord in decerebrate, paralyzed cats. Antidromic stimulation in C6 and the oculomotor nucleus identified the projection pattern of each neuron. Responses to sinusoidal, whole-body rotations in many planes in three-dimensional space were characterized before injection of horseradish peroxidase or Neurobiotin. The spatial response properties of 19 neurons were described by a maximum activation direction vector (MAD), which defines the axis and direction of rotation that maximally excites the neuron. The other two neurons had spatio-temporal convergent behavior and no MAD was calculated. Collateral morphologies were reconstructed from serial frontal sections to reveal terminal fields in the C1 gray matter. Axons gave off multiple collaterals that terminated ipsilaterally to the stem axon. Collaterals of individual axons rarely overlapped longitudinally but projected to similar regions in the ventral horn when viewed in transverse sections. The number of primary collaterals in C1 was different for vestibulo-collic, vestibulo-oculo-collic, and C6-projecting neurons: on average one every 1.34, 1.72, and 4.25 mm, respectively. The heaviest arborization and most terminal boutons were seen in the ventral horn, in laminae VIII and IX. Varicosities on terminal branches in lamina IX were observed adjacent to large cell bodies-putative neck motoneurons-in counterstained tissue. Some collaterals had branches that extended dorsally to lamina VII. Neurons with different spatial properties had terminal fields in different regions of the ventral horn. Axons with type I responses and MADs near those of a semicircular canal pair had widely distributed collateral branches and numerous terminations in the dorsomedial, ventromedial, and spinal accessory nuclei and in lamina VIII. Axons with type I responses that suggested convergent canal pair input, with type II responses, and with spatio-temporal convergent behavior had smaller terminal fields. Some neurons with these more complex spatial properties projected to the dorsomedial and spinal accessory but not to the ventromedial nuclei. Others had focused projections to dorsolateral regions of the ventral horn with few branches in the motor nuclei.

Intradermal 5-HT induces Fos expression in rat dorsal horn neurons not via 5-HT 3 but via 5-HT 2A receptors

We investigated the effects of peripherally administered 5-HT on the secondary neurons in the spinal cord of rats using Fos-like immunoreactivity (FLI) as a marker of neuronal activation. The intradermal administration of 5-HT (30, 60 μg) induced a large number of FLI neurons in the ipsilateral dorsal horn. In animals given 5-HT 2A receptor agonists (DOI: 0.28∼2.8 μmol/kg, α-methyl 5-HT: 0.28∼2.8 μmol/kg) intradermally, immunoreactive neurons were evoked in the same manner as those given 5-HT. Other agonists, including 5-HT 3 receptor agonists ( m-CPG: 16∼32 μmol/kg, 2-methyl 5-HT: 0.0028∼2.8 μmol/kg), did not induce FLI neurons at any dose examined. Furthermore, 5-HT 2A receptor antagonist (ketanserin: 1 mg/kg, i.p.) suppressed the expression of FLI in the dorsal horn caused by peripheral 5-HT, but 5-HT 3 receptor antagonist (tropisetron: 1 mg/kg, i.p.) did not. These findings suggest that the 5-HT-induced nociceptive response is mediated by 5-HT 2A receptors in the periphery.

Projection from trigeminal nuclei to neurons of the mesencephalic trigeminal nucleus in rat

The mesencephalic trigeminal nucleus contains cell bodies of primary somatic sensory neurons that innervate the head region. The neurons resemble dorsal root ganglion cells but a striking difference is the presence of synaptic boutons in the nucleus. The present report demonstrates with anterograde tracers, the existence of a direct trigeminal projection from secondary sensory neurons of the principal and spinal nuclei to the mesencephalic nucleus. Our observations strongly suggest that synaptic contact may be established on the cell bodies as well as on the neurites of the mesencephalic neurons. These pathways could play a modulatory role in the processing of sensory afferent information and in the control of orofacial and/or oculomotor functions.

Recordings from brain stem neurons responding to chemical stimulation of the subarachnoid space.

The subarachnoid space at the base of the skull was perfused continuously with artificial cerebrospinal fluid in anesthetized rats. A combination of inflammatory mediators consisting of histamine, bradykinin, serotonin, and prostaglandin E2 (10(-5) M) at pH of 6.1 was introduced into the flow for defined periods to stimulate meningeal primary afferents. Secondary neurons in the caudal nucleus of the trigeminal brain stem were searched by electrical stimulation of the cornea. Of the units receiving oligosynaptic input from the cornea, 44% were excited by stimulation of the meninges with inflammatory mediators. Most of these units had small receptive fields including cornea and the periorbital region, and their responsiveness was restricted to stimuli of noxious intensity. Three types of responses to stimulation of the meninges with algogenic agents were encountered: responses that did not outlast the stimulus period, responses outlasting the stimulus period for several minutes, and oscillating response patterns containing periods of enhanced and suppressed activity. The response pattern of a unit was reproducible, however, upon repetitive stimulation at 20-min intervals; the response magnitude showed tachyphylaxis upon stimulus repetition. The preparation presented mimics pathophysiolocial states normally accompanied by headache, e.g., subarachnoidal bleeding. Responsiveness of neurons in the caudal nucleus of the trigeminal brain stem to inflammatory mediators may play a role in the generation and maintenance of headache, e.g., migraine.

Contributions of regularly and irregularly discharging vestibular-nerve inputs to the discharge of central vestibular neurons in the alert squirrel monkey.

The discharge of neurons in the vestibular nuclei was recorded in alert squirrel monkeys while they were being sinusoidally rotated at 2 Hz. Type I position-vestibular-pause (PVP I) and vestibular-only (V I) neurons, as well as a smaller number of other type I and type II eye-plus-vestibular neurons were studied. Many of the neurons were monosynaptically related to the ipsilateral vestibular nerve. Eye-position and vestibular components of the rotation response were separated by multiple regression. Anodal currents, simultaneously delivered to both ears, were used to eliminate the head-rotation signals of irregularly discharging (I) vestibular-nerve afferents, presumably without affecting the corresponding signals of regularly discharging (R) afferents. R and I inputs to individual central neurons were determined by comparing rotation responses with and without the anodal currents. The bilateral currents, while reducing the background discharge of all types of neurons, did not affect the mean vestibular gain or phase calculated from a population of PVP I neurons or from a mixed population consisting of all type I units. From this result, it is concluded that I inputs are canceled at the level of secondary neurons. The cancellation may explain why the ablating currents do not affect the gain and phase of the vestibulo-ocular reflex. While cancellation was nearly perfect on a population basis, it was less so in individual neurons. For some neurons, the ablating currents decreased vestibular gain, while for other neurons the vestibular gain was increased. The former neurons are interpreted as receiving a net excitatory (I-EXC) I input, the latter neurons, a net inhibitory (I-INH) input. When compared with the corresponding R inputs, the I inputs were usually small and phase advanced. Phase advances were larger for I-EXC than for I-INH inputs. The sign and magnitude of the I inputs were unrelated to other discharge properties of individual neurons, including discharge regularity and the phase of vestibular responses measured in the absence of the ablating currents. Unilateral currents were used to assess the efficacy of ipsilateral and contralateral pathways. Ipsilateral pathways were responsible for almost all of the effects seen with bilateral currents. The results suggest that the vestibular signals carried by central neurons, even by those neurons receiving a monosynaptic vestibular-nerve input, are modified by polysynaptic pathways.

Uptake of nickel into the brain via olfactory neurons in rats

Intranasal instillation of nickel ( 63Ni 2+ ) in rats resulted in an uptake of the metal in the olfactory epithelium and a migration along primary olfactory neurons to the glomeruli of the olfactory bulb. The metal was then seen to pass to the interior of the bulb and further to the olfactory peduncle, the olfactory tubercle and the rostral parts of the prepiriform, frontal and cingulate corticis. These results indicate that 63Ni 2+ slowly passes to secondary and tertiary olfactory neurons. Intraperitoneal injection of 63Ni 2+ resulted in a low uptake in the brain, without preferential labelling of the olfactory pathways. Inhalation of nickel compounds can impair the olfactory system. An uptake of nickel in the olfactory neurons may underly these lesions.

Immunoreactive excitatory amino acids in the parietal eye of lizards, a comparison with the pineal organ and retina.

The fine structure of the organ and the localization of the excitatory amino acids glutamate and aspartate were studied in the parietal eye of lizards by postembedding immunoelectron microscopy. The parietal eye contains cone photoreceptor cells, secondary neurons, and ependymal and lens cells. The photoreceptors form long inner and outer segments, some of them being paired as "twin-photoreceptors" by zonulae adherentes. Perikarya of neurons bear sensory cilia (containing 9x2+0 pairs of tubules) extending into the intercellular space. No neurohormonal terminals are present in the parietal eye. A higher immunoreactivity to glutamate than to aspartate is found in the photoreceptors and in the secondary neurons of the parietal eye. Glutamate immunogold labeling is more intense in the axonal processes of photoreceptors and neurons and in most of the nerve fibers of the parietal nerve running to the brain stem. Weak aspartate and glutamate immunoreactivity can be detected in the ependymal and lens cells. A similar distribution of immunoreactive amino acids is found in the photoreceptors, secondary neurons, and ependymal glial elements of the pineal organ, and retina of the lateral eye of the same animals. Immunoreactive glutamate accumulates in the axons of photoreceptors and secondary neurons of the parietal eye suggesting that this excitatory amino acid acts as a synaptic mediator in the neural efferentation of the organ. Thus, the efferent light-conducting pathway of the parietal organ is similar to that of the pineal organ and lateral eye retina. As the Mullerian cells of the retina, the ependymal and lens cells of the parietal eye and the ependymal-glial cells of the pineal organ may play a role in the metabolism and/or elimination of excitatory amino acids released by photoreceptors.

Nerve fibre regeneration across the peripheral-central transitional zone.

Neurons cannot negotiate an elongation across the peripheral (PNS)-central nervous system (CNS) transitional zone and grow into or out of the spinal cord in the mature mammal. The astrocytic rich CNS part of the spinal nerve root is most effective in preventing regeneration even of nerve fibres from transplanted embryonic ganglion cells. Regeneration of severed nerve fibres into the spinal cord occurs when the transition zone is absent as in the immature animal. Before the establishment of a transition zone there is also new growth of neuronal processes from dorsal horn neurons distally to the injured dorsal root. Thus the experimental strategy to reestablish spinal cord to peripheral nerve connectivity has been to delete the transitional region and implant severed ventral or dorsal roots into the spinal cord. Dorsal root implantation resulted in reestablished afferent connectivity by new neuronal processes from secondary sensory neurons in the dorsal horn of the spinal cord extending into the PNS. The ability for plasticity in these cells allowed for a concurrent retention of their original rostral projection. Ventral root implantation into the spinal cord corrected deficit motor function. In a long series of experiments performed in different species, the functional restitution was demonstrated to depend on an initial regrowth of motor neuron axons through spinal cord tissue (CNS). These findings have led to the design of a new surgical strategy in cases of traumatic spinal nerve root injuries.

Electrical activity of the sensory afferent pathway in the enteric nervous system.

In this paper we develop a mathematical model for the electrical activity of the afferent pathway, formed from the coupled primary and secondary sensory neurons. The primary sensory neuron possesses the electrical properties of AH neurons and morphological characteristics of Dogiel type II neurons; the secondary sensory neuron displays the tonic type of electrical behavior and has morphological features of Dogiel type III neurons. Free nerve endings of the mechanoreceptor form the receptive field of the pathway. Based on the general principles of the Hodgkin-Huxley description of excitable cells, the model simulates the following sequence of events: stretch of the receptive field initiates the dendritic potential at the mechanoreceptors; the excitation causes soma action potential development at the primary sensory neuron which is followed by soma action potential generation at the secondary sensory neuron. Numerical calculation have shown that the model is capable of reproducing different electrical patterns within the pathway under normal physiological conditions and after treatment with charybdotoxin, iberiotoxin, tetrodotoxin, omega-conotoxin GVIA, A1-A2 purinoceptor agonists, a protein kinase C activator, and a delta-opioid receptor agonist. Comparison of the computational results with the results of experiments conducted on the neurons of the submucous and myenteric plexi of the small bowel demonstrates their good qualitative and quantitative agreement.

Transplanted Glial Scar Impedes Olfactory Bulb Reinnervation

The olfactory system is the only region of the mammalian central nervous system in which degeneration of the primary sensory neurons results in the development of new neurons and reinnervation of the secondary sensory neurons. Axotomy of the olfactory nerve at the cribriform plate does not cause the formation of a glial scar which blocks nerve regeneration. The purpose of this study was to determine whether a glial scar that formed in the optic nerve would suppress axonal regeneration when transplanted to the site of olfactory nerve axotomy. Primary olfactory neurons were axotomized along the cribriform plate in adult rats. A compact glial scar formed by transection of an adult rat optic nerve 50 to 60 days prior to removal was transplanted into the olfactory nerve axotomy site. The rats were allowed to survive for 1, 2, 3, or 4 weeks. Transport of horseradish peroxidase (HRP) from the nasal cavity by the olfactory neurons was used to examine the temporal and spatial pattern of regeneration of the olfactory nerve after axotomy and axotomy followed by glial scar transplantation. Twenty-one days after olfactory nerve axotomy, HRP was found in the glomerular layer where the primary olfactory axons synapse on the apical dendrites of the secondary olfactory neurons. In the presence of the transplanted glial scar, HRP labeling was not found in certain glomeruli even at 4 weeks postaxotomy. Glial scars formed within the optic nerve impede reinnervation of the olfactory bulb by neurons which have an exceptional regenerative capacity due in part to the ensheathing glia.

Temperature-sensitive parainfluenza type 1 vaccine virus directly accesses the central nervous system by infecting olfactory neurons.

Immunohistochemical investigation showed that intranasal inoculation of mice with a temperature-sensitive (ts) mutant of parainfluenza type 1 vaccine virus resulted in infection of some olfactory neurons as well as respiratory epithelial cells. It also disclosed the presence of viral antigens in glomeruli of the olfactory bulb but not in the secondary neurons (mitral and tufted cells). Polymerase chain reaction demonstrated the persistence of virus-specific nucleic acids in the olfactory bulb. These observations lead to the conclusion that parainfluenza virus, even with a ts phenotype, gains access to the central nervous system by infecting olfactory neurons.

Oral inoculation with herpes simplex virus type 1 infects enteric neuron and mucosal nerve fibers within the gastrointestinal tract in mice.

Herpes simplex virus type 1 (HSV-1) is commonly encountered first during childhood as an oral infection. After this initial infection resolves, the virus remains in a latent form within innervating sensory ganglia for the life of the host. We have previously shown, using a murine model, that HSV-1 placed within the lumen of the esophagus gains access to nerves within the gut wall and establishes a latent infection in sensory ganglia (nodose ganglia) of the tenth cranial nerve (R. M. Gesser, T. Valyi-Nagy, S. M. Altschuler, and N. W. Fraser, J. Gen. Virol. 75:2379-2386, 1994). Peripheral processes of neurons in these ganglia travel through the vagus nerve and function as primary sensory receptors in most of the gastrointestinal tract, relaying information from the gut wall and mucosal surface to secondary neurons within the brain stem. In the work described here, we further examined the spread of HSV-1 through the enteric nervous system after oral inoculation. By immunohistochemistry, HSV-1 was found to infect myenteric ganglia in Auerbach's plexus between the inner and outer muscle layers of the gut wall, submucosal ganglia (Meisner's plexus), and periglandular ganglion plexuses surrounding submucosal glands. Virus-infected nerve fibers were also seen projecting through the mucosal layer to interact directly with surface epithelial cells. These intramucosal nerve fibers may be a conduit by which intraluminal virus is able to gain access to the enteric nervous system from the gastrointestinal lumen.