Collateral branching in axonal projections to spinal cord from paramedian reticular nucleus neurons

Experiments were done in cats to identify neurons in the paramedian reticular nucleus (PRN) sending collateral axons to the region of the intermediolateral nucleus (IML) at different levels of the thoracic cord by using lectin-conjugated horseradish peroxidase (HRP) and double-labeling fluorochrome histochemistry to retrogradely label PRN neurons. Injections of Fast blue (FB) into the spinal cord at the T2 level centered in the region of the IML were coupled with injections of Nuclear yellow (NY) into the ipsilateral cord at either the T4 or T7 levels centered in the region of the IML. Neurons in the PRN retrogradely labeled after diffusion of HRP into the region of the IML at the T2 level were observed throughout the rostrocaudal extent of the ventral PRN. In addition, a few labeled neurons were noted in the ventral portion of the dorsal PRN. About 40% of the neurons in the PRN which were labeled with FB after an injection at the T2 level were also labeled with NY injected into the cord in further caudal segments. These data suggest that the PRN may exert its influence on the cardiovascular system partly through collateral axonal branches to widely separated populations of sympathetic preganglionic neurons in different spinal segmental levels.     

Cerebellar, medullary and spinal afferent connections of the paramedian reticular nucleus in the cat

The topographic organization of afferent projections from the deep cerebellar nuclei, medulla oblongata and spinal cord to the paramedian reticular nucleus (PRN) of the cat was studied using the horseradish peroxidase (HRP) method of retrograde labelling. Discrete placements of HRP within each of the dorsal (dPRN) and ventral (vPRN) regions of the PRN showed some segregation of input. The deep cerebellar nuclei project in a predominantly contralateral fashion upon the PRN. A small but significant ipsilateral fastigial afferent component is also present. The fastigial and dentate nuclei contribute the majority of fibers to the dPRN whereas the interposed nucleus provides very little. The vPRN receives a relatively uniform input from all 3 cerebellar nuclei. Both lateral vestibular nuclei contribute the majority of fibers from the vestibular nuclear complex largely from their dorsal division. Additional input arises from bilateral medial and inferior vestibular nuclei. The vPRN receives relatively more fibers from the inferior vestibular nuclei than does the dPRN while inputs from the medial vestibular nuclei are comparably sparse. The PRN receives bilateral projections from the nucleus intercalatus (of Staderini). A significant projection to the contralateral PRN occurs from the ventrolateral subnucleus of the solitary complex and its immediate vicinity. Additional sources of medullary afferent input include the lateral, gigantocellular and magnocellular tegmental fields, the contralateral PRN and the raphe nuclei. Sites of origin of spinal afferents to the dPRN are bilaterally distributed mainly within Rexed's laminae VII and VIII of the cervical cord whereas those to the vPRN are confined largely to the medial portion of the contralateral lamina VI in the C1 segment. A few labelled cells are found in the thoracolumbar cord with those to the vPRN being more caudal. These data provide the neuroanatomical substrate for a better understanding of the functional role of the PRN in mediating cardiovascular responses appropriate to postural changes.     

Modulatory actions of the gigantocellular reticular nucleus on baroreceptor reflexes in the cat

Threshold visual acuity for three cats which were reared from birth to 4–12 months of age with bilateral lid closure was measured and compared to visual acuity in three cats which had the use of a non-deprived eye. The results indicate that binocular deprivation (BD) results in significant deficits in visual acuity which are proportional to the duration of deprivation. Threshold visual acuities were 3.7 cycles/deg. following 4 months of BD, 3.25 cycles/deg. following 7 months of BD and 2.55 cycles/deg. following 12 months of BD compared to acuities of 6.0, 6.5 and 6.8 cyclesdeg. for cats using a non-deprived eye. All BD cats had recovered from the initial visuomotor deficits, seen in these cats and reported in the literature, following lid-parting. The implication of such deficits in visual acuity on visual discrimination learning in BD cats is discussed.     

Paresis of lateral gaze alternating with so-called posterior internuclear ophthalmoplegia. A partial paramedian pontine reticular formation-abducens nucleus syndrome

Summary A patient with multiple myeloma developed gaze paresis to the left with slowed saccades and gaze-paretic nystagmus, which alternated with abduction palsy in the left eye (with preserved oculocephalic deviation) and dissociated adducting nystagmus in the right eye, suggesting so-called posterior internuclear ophthalmoplegia. At autopsy multiple small infarcts were found with partial destruction of the left paramedian pontine reticula formation (PPRF) extending towards the abducens nucleus, which was involved only in its inferior pole. The medial longitudinal fasciculus and other oculomotor structures were spared. It is suggested that slowing of all ipsilateral saccades with gaze-paretic nystagmus corresponded to partial destruction of the PPRF, and that intermitted abduction palsy in the ipsilateral eye with adduction nystagmus in the fellow eye was due to intermittant dysfunction of the abducens nucleus. Involvement of voluntary saccades, pursuit movements and vestibulo-ocular responses may be dissociated in partial lesions of the abducens nucleus.     

Inhibition of thalamic ventrobasal complex neurons by glutamate infusion into the thalamic reticular nucleus in rats

In urethane-anesthetized rats a 0.36-mm metallic cannula for infusion was positioned in the somatosensory component of the thalamic reticular nucleus (sTR), where movement of the vibrissae evoked neuronal discharge. Infusion there of 0.125-0.5 microliter of a 50 mM solution of glutamate over a 1-min period suppressed both spontaneous and evoked discharge of neurons in the ventrobasal complex (VB), but only for those which also responded to vibrissal stimulation. VB neurons activated by somatosensory stimuli at other locations were unaffected. Thus, excitation of neurons in sTR inhibits those in VB, but the effect appears to be highly coordinated somatotopically.     

Descending projections from the dorsolateral pontine tegmentum to the paramedian reticular nucleus of the caudal medulla in the cat.

We examined whether the dorsolateral pontine cholinergic cells project to the paramedian reticular nucleus (PRN) of the caudal medulla. In 3 cats, wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) was injected into the PRN and we noted cells in the dorsolateral pons that contained the HRP reaction product, cells that were immunolabeled for choline acetyltransferase (ChAT), and cells that contained the HRP reaction product and were ChAT positive. We found cholinergic projections from the pedunculopontine tegmental and laterodorsal tegmental nuclei to the PRN. This finding is consistent with studies indicating a cholinoceptive region in the medial medulla mediating suppression of muscle tone. Our results demonstrate that this medullary region has monosynaptic input from pontine neurons implicated in generating the atonia of rapid eye movement sleep.     

Reduction of blood PO2 decrease and PCO2 increase during asphyxia by paramedian reticular nucleus in cats

Effects of activation of paramedian reticular nucleus (PRN) on the systemic arterial blood pressure (SAP), heart rate, renal nerve activity (RNA), and changes of the partial pressure of the arterial blood oxygen (PO2) and carbon dioxide (PCO2) during asphyxia were studied in cats anesthetized with chloralose (40 mg/kg) and urethane (400 mg/kg). During a 35-s period of asphyxial anoxia, SAP and RNA increased while heart rate decreased significantly. The arterial blood PO2 decreased by 64.6 +/- 4.7% while the PCO2 increased by 54.6 +/- 6.3%. Electrical stimulation of PRN produced a mild to moderate decrease of the SAP, heart rate, and RNA, but arterial PO2 and PCO2 did not change significantly. When PRN was stimulated simultaneously with asphyxia, increases of SAP and RNA and changes of blood gases subsequent to asphyxia reduced significantly. Arterial PO2 decreased only 54.0 +/- 4.9% while the PCO2 increased 39.4 +/- 10.5% (p < 0.01). Similar effects were observed in the venous blood from inferior vena cava. In addition, when the arteriovenous difference of PO2 and PCO2 was compared, simultaneous PRN stimulation during asphyxia produced a higher PO2 reserve (66.3%) and less PCO2 production (-7%) than without PRN stimulation; PO2 54.2%, PCO2 (-2.9%). The results suggest that PRN is a structure that can exert inhibition over a wide spectrum of body functions; not only autonomic system but probably also metabolism.     

The topographic organization of spinal afferents to the lateral reticular nucleus of the cat

The topographic organization of spinal afferents to the lateral reticular nucleus (LRN) has been reexamined in 34 adult cats. Two modifications of the Nauta technique were used to show secondary terminal degeneration resulting from circumscribed lesions at various levels of the spinal cord. The results demonstrate that the “inner segment” of LRN corresponding roughly to Brodal's magnocellular portion, receives fibers from spinal segments C₁–D₃, while the “outer segment” corresponding approximately to Brodal's parvocellular protion receives fibers from spinal levels below L₃. The “middle segment” — a transitional zone between the two former portions — represents the spinal segments D₄–L₃. The ascending fibers terminate predominantly on the ipsilateral side; only few degenerated elements are noted within the contralateral nucleus. The subtrigeminal portion does not seem to receive afferent fibers from the spinal cord. This finding raises the question of nomenclature, which is briefly discussed in the light of the classical “nucleus funiculi lateralis” concept. Finally, the present data are consistent with electrophysiological data of Oscarsson, Rosén and collaborators according to which LRN represents spinal levels of convergent inputs from large as well as bilateral receptive fields rather than somatotopically arranged projections from peripheral sense organs.     

The thalamic reticular nucleus and schizophrenia

Background: The thalamic reticular nucleus (TRN) is a shell-shaped gamma amino butyric acid (GABA)ergic nucleus, which is uniquely placed between the thalamus and the cortex, because it receives excitatory afferents from both cortical and thalamic neurons and sends inhibitory projections to all nuclei of the dorsal thalamus. Method: A review of the evidence suggesting that the TRN is implicated in the neurobiology of schizophrenia. Results: TRN-thalamus circuits are implicated in bottom-up as well as top-down processing. TRN projections to nonspecific nuclei of the dorsal thalamus mediate top-down processes, including attentional modulation, which are initiated by cortical afferents to the TRN. TRN-thalamus circuits are also involved in bottom-up activities, including sensory gating and the transfer to the cortex of sleep spindles. Intriguingly, deficits in attention and sensory gating have been consistently found in schizophrenics, including first-break and chronic patients. Furthermore, high-density electroencephalographic studies have revealed a marked reduction in sleep spindles in schizophrenics. Conclusion: On the basis of our current knowledge on the molecular and anatomo-functional properties of the TRN, we suggest that this thalamic GABAergic nucleus may be involved in the neurobiology of schizophrenia.     

The origin of brainstem afferents of the paramedian pontine reticular formation in the cat

Transcannular microinjections of horseradish peroxidase (HRP) were made into the paramedian pontine reticular formation (PPRF) in adult cats to determine the origin of the principal sources of inputs to this important preoculomotor center for the production of saccadic eye movements. Retrogradely labeled cells were observed in numerous oculomotor-related structures, including the prerubral field (rostral interstitial nucleus of the medial longitudinal fasciculus), nucleus of Darkschewitsch, nucleus of the posterior commissure, deep superior colliculus, supraoculomotor ventral periaqueductal gray, contralateral paramedian pontine reticular formation, pontine raphe and dorsal medial pontine tegmentum medial to the abducens nucleus (purported to contain omnipause neurons), cell group Y, and the perihypoglossal complex (nucleus prepositus hypoglossi). Other sources of afferents to the region included the zona incerta, lateral and medial habenular nuclei, medial hypothalamus, medial mammillary nucleus, nucleus cuneiformis, medial medullary reticular formation, and the medial and lateral cerebellar nuclei. The results are discussed in terms of the potential influence of these nuclei on the control of eye movement.     

Brainstem and spinal pathways mediating descending inhibition from the medullary lateral reticular nucleus in the rat

The lateral reticular nucleus (LRN) in the caudal ventrolateral medulla has been implicated in descending monoaminergic modulation of spinal nociceptive transmission. Experiments were undertaken to examine the organization of pontine and spinal pathways mediating inhibition of the tail-flick (TF) reflex from the LRN in rats lightly anesthetized with pentobarbital. Microinjections of the local anesthetic lidocaine ipsilaterally or bilaterally into the dorsolateral pons blocked stimulation-produced inhibition of the TF reflex from the nucleus locus coeruleus/subcoeruleus (LC/SC), but had no effect on descending inhibition produced by microinjection of glutamate into the LRN. Thus, adrenergic modulation of the TF reflex from the LRN is not mediated by activation of spinopetal noradrenergic neurons in the LC/SC. The funicular course of descending inhibition produced by focal electrical stimulation in the LRN was studied in separate groups of rats by reversibly (local anesthetic blocks) or irreversibly (surgical transection) compromising conduction in the dorsolateral funiculi (DLFs) at the level of the cervical spinal cord. Bilateral lidocaine blocks in the DLFs significantly shortened control TF latencies and more than doubled the intensity of electrical stimulation in the LRN necessary to inhibit the TF reflex (153 +/- 29% increase from control); changes in these parameters produced by unilateral blocks of the DLFs were not statistically significant. Ipsilateral or bilateral transections of the DLFs significantly increased the intensity of electrical stimulation in the LRN to inhibit the TF reflex (110 +/- 24% and 265 +/- 46% from control, respectively). Neither lidocaine blocks nor transections of the DLFs completely blocked the descending inhibitory effects of electrical stimulation in the LRN. The DLFs appear to carry fibers mediating LRN stimulation-produced inhibition of the TF reflex as well as tonic descending inhibition of spinal reflexes. The results of the present study indicate that (1) adrenergic modulation of the nociceptive TF reflex from the LRN does not depend on a rostral loop through the pontine LC/SC, and (2) descending inhibitory influences from the LRN are contained in, but not confined to, the dorsal quadrants of the spinal cord.     

Ocular flutter associated with a localized lesion in the paramedian pontine reticular formation

Ocular flutter is a rare horizontal eye movement disorder characterized by rapid saccadic oscillations. It has been hypothesized that it is caused by loss of "pause" neuronal inhibition of "burst" neuron function in the paramedian pontine reticular formation (PPRF); however, there have been no imaging studies confirming such anatomical localization. We report the case of a woman with an acute attack of multiple sclerosis associated both with ocular flutter and a circumscribed pontine lesion, mainly involving the PPRF on magnetic resonance imaging. As she recovered from the attack, both the midline pontine lesion and the ocular flutter dramatically improved. This case is the first clear evidence that at least some cases of ocular flutter are due to lesions involving the PPRF.     

Suppression of limbic motor seizures by electrical stimulation in thalamic reticular nucleus

Kindling is a model of temporal lobe epilepsy in which repeated electrical stimulations in limbic areas lead to progressive increase of seizure susceptibility, culminating in generalized convulsions and the establishment of a permanent epileptic syndrome. We studied here the effect of stimulations in the thalamic reticular nucleus (TRN) on the development of seizures and hippocampal hyperexcitability in kindling elicited from the ventral hippocampus in rats. Animals given 12 kindling stimulations per day with 30-min intervals for 4 consecutive days developed generalized convulsions on day 4. Stimulations in TRN delivered simultaneously with those in the hippocampus induced marked suppression of seizure generalization. Similarly, the number of generalized seizures and the duration of behavioral convulsions were reduced when rats subjected to 40 kindling stimulations with 5-min intervals during about 3 h were costimulated in the TRN. The anticonvulsant effect of TRN costimulation was detected also when rats were test-stimulated in the hippocampus at 24 h and 2 and 4 weeks after the initial 40 hippocampal stimulations. Our data provide the first evidence that TRN stimulations can act to suppress limbic motor seizures in hippocampal kindling and suggest a new approach for seizure control in temporal lobe epilepsy.     

Cardiovascular afferent and fastigial nucleus inputs to paramedian reticulospinal neurons

In chloralose anesthetized, paralyzed and artificially ventilated cats, the region of the paramedian reticular nucleus (PRN) was systematically explored for single units antidromically activated by electrical stimulation of histologically verified sites in the intermediate gray region of the upper thoracic cord (T2). These antidromically identified units were then tested for their orthodromic responses to electrical stimulation of ipsilateral carotid sinus nerve (CSN) and of pressor sites in the contralateral fastigial nucleus (FN). Sixty-two histologically verified single units, located predominantly in the caudal half of the ventral PRN, were antidromically activated with latencies corresponding to a mean conduction velocity of 36.4 +/- 2.1 m/s. Of these units 25 (40%) were excited orthodromically by stimulation of the CSN and/or FN: 5 to stimulation of the CSN only (mean latency, 18.3 +/- 9.9 ms), 6 to stimulation of the FN only (mean latency, 7 +/- 1.7 ms), and 14 to stimulation of both the CSN and FN (mean latencies, 12.3 +/- 2.9 ms and 8.4 +/- 1 ms, respectively). These data provide electrophysiological evidence for the existence of PRN reticulo-spinal neurons that integrate and relay cardiovascular afferent information from the CSN and FN to spinal autonomic neurons.     

Projections of the lateral reticular nucleus to the cochlear nucleus in rats

The lateral reticular nucleus (LRN) resides in the rostral medulla and caudal pons, is implicated in cardiovascular regulation and cranial nerve reflexes, and gives rise to mossy fibers in the cerebellum. Retrograde tracing data revealed that medium-sized multipolar cells from the magnocellular part of the LRN project to the cochlear nucleus (CN). We sought to characterize the LRN projection to the CN using BDA injections. Anterogradely labeled terminals in the ipsilateral CN appeared as boutons and mossy fibers, and were examined with light and electron microscopy. The terminal field in the CN was restricted to the granule cell domain (GCD), specifically in the superficial layer along the anteroventral CN and in the granule cell lamina. Electron microscopy showed that the smallest LRN boutons formed 1-3 synapses, and as boutons increased in size, they formed correspondingly more synapses. The largest boutons were indistinguishable from the smallest mossy fibers, and the largest mossy fiber exhibited 15 synapses. Synapses were asymmetric with round vesicles and formed against thin dendritic profiles characterized by plentiful microtubules and the presence of fine filopodial extensions that penetrated the ending. These structural features of the postsynaptic target are characteristic of the terminal dendritic claw of granule cells. LRN projections are consistent with known organizational principles of non-auditory inputs to the GCD.