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Synaptic plasticity of the interpositorubral pathway functionally related to forelimb flexion movements.

1. Some connections from the afferents to the magnocellular red nucleus (RNm), like the corticorubral synapses, have plastic properties that are thought to contribute to long-term changes such as functional readaptation, motor learning, and the establishment of conditioned responses. Because previous studies have focused on corticorubral synaptic reorganization after these events, we attempted to investigate cerebellorubral connections in intact adult cats during associative conditioning by pairing electrical stimulation of interpositus nucleus [the conditional stimulus (CS)] with electrical simulation of the forelimb [the unconditional stimulus (UCS)]. A large increase in the amplitude of the forelimb flexion (conditioned response) induced by the CS was observed after several days of paired CS-UCS presentations. 2. For this purpose, both behavioral and electrophysiological methods were used to correlate synaptic plasticity with changes in the motor responses. The somatotopically organized sensorimotor network functionally related to the control of the elbow joint movements was studied in awake adult cats. This circuit was defined on the basis of sites at which elbow flexions could be evoked both as a CS and a UCS. The CS was applied in the cerebellar interpositus nucleus (IN) site and the UCS was given to the skin on the dorsum of the distal part of the forepaw. Daily classical conditioning consisted of repetitive pairings of CS and UCS with an interstimulus interval (ISI) of 100 ms. 3. The transmission efficacy resulting from the conditioning was tested in various targets of the cerebellar efferent pathway, including the RNm. Electrophysiological responses evoked in these relay structures by the CS and the forelimb angular deviations were simultaneously recorded throughout each daily conditioning session. The surface areas of the rubral responses to CS and the percentage response rate, the angular deviation (amplitude), and the latency of the motor responses were systematically measured throughout the conditioning procedure. Test sessions were also performed before and after each period of conditioning. Quantification and statistical analysis were carried out to determine whether changes observed in interpositorubral synaptic transmission and in the motor responses evoked by the CS were correlated. 4. Daily repetition of paired CS and UCS according to a predefined and fixed temporal schedule led to an increase in the response rate and amplitude of the forelimb flexions. A procedure with repeated presentation of CS preceded by UCS was used to produce extinction of the enhanced motor responses. The associative nature of these changes was confirmed by the fact that the CS given alone for 11 days in a control condition failed to produce any modification of the motor response. 5. The changes in the flexion movements were accompanied by a nearly parallel increase of the amplitude of the "postsynaptic field potentials" evoked in the RNm by the CS (IN stimulation). Changes in the transmission efficacy of the interpositorubral synapses stayed stable even after several days of interruption and remained constant up the extinction period. Changes affecting both the motor and the central responses were significantly correlated, suggesting that modifications in the interpositorubral transmission efficacy might be one of the plastic correlates of forelimb flexion conditioning. 6. Examination of the neuronal excitability within either the IN or the RNm or in the spinal cord failed to show any evidence of facilitation suggesting that the increases in the postsynaptic rubral field potential were attributable to a plasticity of the interpositorubral connections. The long-lasting duration of the increase of cerebellorubral synaptic transmission suggests that structural changes were induced by conditioning in the intact animal. (ABSTRACT TRUNCATED)

Animals↗

Excitatory effects of motilin in the hippocampus on gastric motility in rats.

Intestinal motilin is known to stimulate gastrointestinal motility. Recently, it was shown that the motilin gene and the motilin receptor are expressed in various regions of the brain. We studied whether motilin can activate pathways in the rat hippocampus to stimulate gastric motility. Gastric motility was monitored in conscious rats, whereas extracellular electrical activity recordings of the hippocampus were performed on anaesthetized rats to measure the influence of microinjection of motilin and CCK-8 into the hippocampus and into the cerebral ventricles. We found that neurons in the CA3 region of the hippocampus are sensitive to gastric distension, and that injection of motilin into the hippocampus increased the amplitude of gastric contractions by 35.3+/-6.8%, while CCK-8 injection inhibited motility by -27.3+/-6.8%. The hippocampal motilin-induced stimulation of gastric motility (30.6+/-5.5%) was completely abolished by subdiaphragmal vagotomy (-2.8+/-4.4%) but unaffected by the intravenously applied receptor blockers atropine, phentolamine and propranolol. In vivo extracellular recordings of gastric distension-responsive CA3 neurons revealed that intracerebroventricular administration of motilin increased firing while CCK-8 inhibited firing. These opposite effects of motilin and CCK-8 fit with the nature of the actions of these gut-brain peptides on gastric motility. Our findings suggest that the stimulation of gastric motility by motilin administered in the hippocampus reflects the existence of a functional interaction between the hippocampus and a vago-vagus reflex running via a noncholinergic and nonadrenergic efferent pathway.

Action Potentials↗

Characterization of vagal pathways mediating gastric accommodation reflex in rats.

1. We investigated the vagal pathways mediating the gastric accommodation reflex in the rat stomach. 2. Gastric distension (6 ml) evoked an increase of 9.0 +/- 1.0 cmH2O of intragastric pressure in vivo. Pretreatment with tetrodotoxin (TTX) caused a significant pressure increase by gastric distension, reaching 17.0 +/- 1.7 cmH2O, suggesting mediation by neural pathways. 3. The pressure increase evoked by gastric distension was significantly enhanced in vivo by acute truncal vagotomy (TV), hexamethonium (C6), and NG-nitro-L-arginine methyl ester (L-NAME), but not by vasoactive intestinal polypeptide (VIP) antiserum, guanethidine, or splanchnicotomy. 4. Gastric distension (6 ml) evoked a much larger intragastric pressure in the denervated, vascularly isolated, perfused rat stomach in vitro. Intra-arterial application of TTX and L-NAME did not cause further pressure increases evoked by gastric distension. 5. The pressure increase evoked by gastric distension remained high 2 weeks after TV in vivo. However, the accommodation reflex was fully restored 4 weeks after TV in vivo. This reflex was antagonized by TTX, C6 and L-NAME, but not by VIP antiserum, guanethidine and splanchnicotomy. 6. Similar to in vivo studies, gastric distension caused a smaller increase in intragastric pressure in response to gastric distension in the denervated, vascularly isolated, perfused stomach obtained from rats 4 weeks after vagotomies in vitro. The pressure increase evoked by gastric distension was significantly enhanced by L-NAME, hexamethonium and TTX. 7. It is suggested that the vago-vagal reflex plays an important role in mediating the accommodation reflex. This involves a vagal efferent pathway that uses nitric oxide as a final neurotransmitter mediating gastric relaxation in intact rats. It is also suggested that the adaptive mechanism mediating the accommodation reflex following vagotomy occurs in the gastric myenteric plexus.

Adaptation, Physiological↗

Expression of glutamate receptor subunit/subtype messenger RNAS for NMDAR1, GLuR1, GLuR2 and mGLuR5 by accumbal projection neurons.

Nucleus accumbens neurons are the targets of glutamatergic inputs. By coupling in situ hybridization for glutamate receptor mRNAs with retrograde transport of Fluoro-Gold, the present study examined the relationship between the distribution patterns of glutamate receptor subtypes/subunits and the output pathways of the nucleus accumbens to the ventral pallidum and ventral tegmental area. Following iontophoretic deposits of Fluoro-Gold into the ventral pallidum, neurons in both the nucleus accumbens shell and core were retrogradely labeled. A high percentage of accumbens neurons retrogradely labeled from the ventral pallidum were double-labeled for mRNAs encoding for mGluR5 (82+/-4.1%), NMDAR1 (71+/-3.5%), GluR1 (70+/-6.1%) and GluR2 (76+/-3.6%). No significant difference in the proportion of double-labeled neurons between the core and shell was observed. Following the deposit of Fluoro-Gold into the ventral tegmental area, only the accumbens shell neurons were retrogradely labeled. The proportion of neurons expressing NMDAR1, GluR1 and GluR2 were somewhat less in the projection to the ventral tegmental area compared to the ventral pallidum since approximately 60% of the neurons retrogradely-labeled from the ventral tegmental area expressed these transcripts. In contrast to the high proportion of mGluR5-containing neurons in the nucleus accumbens innervating the ventral pallidum, only half of the neurons projecting to the ventral tegmental area expressed mGluR5. These data show that accumbens neurons innervating the ventral pallidum and ventral tegmental area differ in the relative proportion of expressed mRNA encoding mGluR5, implying differential postsynaptic impact by glutamate transmission on neurons contributing to the two major efferent pathways of the nucleus accumbens.

Animals↗

Sensorimotor integration in the primate superior colliculus. I. Motor convergence.

Orienting movements of the eyes and head are made to both auditory and visual stimuli even though in the primary sensory pathways the locations of auditory and visual stimuli are encoded in different coordinates. This study was designed to differentiate between two possible mechanisms for sensory-to-motor transformation. Auditory and visual signals could be translated into common coordinates in order to share a single motor pathway or they could maintain anatomically separate sensory and motor routes for the initiation and guidance of orienting eye movements. The primary purpose of the study was to determine whether neurons in the superior colliculus (SC) that discharge before saccades to visual targets also discharge before saccades directed toward auditory targets. If they do, this would indicate that auditory and visual signals, originally encoded in different coordinates, have been converted into a single coordinate system and are sharing a motor circuit. Trained monkeys made saccadic eye movements to auditory or visual targets while the activity of visual-motor (V-M) cells and saccade-related burst (SRB) cells was monitored. The pattern of spike activity observed during trials in which saccades were made to visual targets was compared with that observed when comparable saccades were made to auditory targets. For most (57 of 59) V-M cells, sensory responses were observed only on visual trials. Auditory stimuli originating from the same region of space did not activate these cells. Yet, of the 72 V-M and SRB cells studied, 79% showed motor bursts prior to saccades to either auditory or visual targets. This finding indicates that visual and auditory signals, originally encoded in retinal and head-centered coordinates, respectively, have undergone a transformation that allows them to share a common efferent pathway for the generation of saccadic eye movements. Saccades to auditory targets usually have lower velocities than saccades of the same amplitude and direction made to acquire visual targets. Since fewer collicular cells are active prior to saccades to auditory targets, one determinant of saccadic velocity may be the number of collicular neurons discharging before a particular saccade.

Acoustic Stimulation↗

Electroacupuncture at ST-36 accelerates colonic motility and transit in freely moving conscious rats.

Acupuncture is useful for functional bowel diseases, such as constipation and diarrhea. However, the mechanisms of beneficial effects of acupuncture on colonic function have scarcely ever been investigated. We tested the hypothesis that electroacupuncture (EA) at ST-36 stimulates colonic motility and transit via a parasympathetic pathway in conscious rats. Hook-shaped needles were inserted at bilateral ST-36 (lower limb) or BL-21 (back) and electrically stimulated at 10 Hz for 20 min. We also studied c-Fos expression in response to EA at ST-36 in Barrington's nucleus of the pons. EA at ST-36, but not BL-21, significantly increased the amplitude of motility at the distal colon. The calculated motility index of the distal colon increased to 132 +/- 9.9% of basal levels (n = 14, P < 0.05). In contrast, EA at ST-36 had no stimulatory effects in the proximal colon. EA at ST-36 significantly accelerated colonic transit [geometric center (GC) = 6.76 +/- 0.42, n = 9, P < 0.001] compared with EA at BL-21 (GC = 5.23 +/- 0.39, n = 7). The stimulatory effect of EA at ST-36 on colonic motility and transit was abolished by pretreatment with atropine. EA-induced acceleration of colonic transit was also abolished by extrinsic nerve denervation of the distal colon (GC = 4.69 +/- 0.33, n = 6). The number of c-Fos-immunopositive cells at Barrington's nucleus significantly increased in response to EA at ST-36 to 8.1 +/- 1.1 cells/section compared with that of controls (2.4 +/- 0.5 cells/section, n = 3, P < 0.01). It is concluded that EA at ST-36 stimulates distal colonic motility and accelerates colonic transit via a sacral parasympathetic efferent pathway (pelvic nerve). Barrington's nucleus plays an important role in mediating EA-induced distal colonic motility in conscious rats.

Acupuncture Points↗

Induction of dopamine D3 receptor expression as a mechanism of behavioral sensitization to levodopa.

In rats with unilateral lesions of the nigrostriatal dopamine pathway with 6-hydroxydopamine, the motor stimulating effects of levodopa, an indirect dopamine receptor agonist, evidenced by contraversive rotations, become enhanced upon repeated intermittent administration. However, the mechanisms of this behavioral sensitization are essentially unknown. We show that development of sensitization is accompanied by a progressive appearance of D3 receptor mRNA and binding sites, visualized by in situ hybridization and 7-[3H] hydroxy-N,N-di-n-propyl-2-aminotetralin autoradiography, respectively, occurring in the denervated caudate putamen, a brain area from which this receptor subtype is normally absent. Development and decay of these two processes occur with closely parallel time courses, whereas there were no marked changes in D1 or D2 receptor mRNAs. D3 receptor induction by levodopa is mediated by repeated D1 receptor stimulation, since it is prevented by the antagonist SCH 33390 and mimicked by the agonist SKF 38393, but not by two D2 receptor agonists. The enhanced behavioral response to levodopa is mediated by the newly synthesized D3 receptor, since it is antagonized by nafadotride, a preferential D3 receptor antagonist, in low dosage, which has no such effect before D3 receptor induction. D3 receptor induction and behavioral sensitization are also accompanied by a sustained enhancement of prodynorphin mRNA level and a progressively decreasing expression of the preprotachykinin gene. We propose that imbalance between dynorphin and substance P release from the same striatonigral motor efferent pathway, related to D3 receptor induction, is responsible for behavioral sensitization.

Animals↗

Physiological assessment of aspects of autonomic function in patients with secondary progressive multiple sclerosis.

A detailed non-invasive study of systemic and regional haemodynamic responses to a range of autonomic tests which assess sympathetic and parasympathetic pathways (mental arithmetic, cutaneous cold, isometric exercise, deep breathing, Valsalva manoeuvre and head-up tilt) were performed in ten patients with secondary progressive multiple sclerosis and ten age- and sex-matched healthy normal subjects (controls). Blood pressure rose in controls during the pressor tests and was maintained during tilt. In six out of ten patients with multiple sclerosis blood pressure was unchanged during one or more of the three pressor tests, but was maintained in all during tilt. In the controls, superior mesenteric artery blood flow fell during pressor tests and head-up tilt. In multiple sclerosis patients, superior mesenteric artery blood flow did not change during pressor tests but fell during tilt. Cardiac index rose during isometric exercise and fell during head-up tilt in controls. Forearm blood flow rose during mental arithmetic in the controls only, but fell during tilt in both groups. Individual analysis indicated that of the ten multiple sclerosis patients, four had responses during the pressor tests similar to controls. Responses to deep breathing and to the Valsalva manoeuvre in controls and multiple sclerosis patients were similar. We conclude that some patients with an aggressive and disabling form of multiple sclerosis have selective autonomic dysfunction, in particular involving pressor responses, despite the lack of postural hypotension. The autonomic abnormality is likely to involve central autonomic interconnections rather than afferent or sympathetic efferent pathways. Further clarification of the nature, site and progression of these lesions is needed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Localization of NADPH diaphorase in the lumbosacral spinal cord and dorsal root ganglia of the cat.

The distribution of NADPH-d activity in the spinal cord and dorsal root ganglia of the cat was studied to evaluate the role of nitric oxide in lumbosacral afferent and spinal autonomic pathways. At all levels of the spinal cord NADPH-d staining was present in neurons and fibers in the superficial dorsal horn and in neurons around the central canal and in the dorsal commissure. In addition, the sympathetic autonomic nucleus in the rostral lumbar segments exhibited prominent NADPH-d cellular staining whereas the parasympathetic nucleus in the sacral segments was not well stained. The most prominent NADPH-d activity in the sacral segments occurred in fibers extending from Lissauer's tract through laminae I along the lateral edge of the dorsal horn to lamina V and the region of the sacral parasympathetic nucleus. These fibers were very similar to VIP-containing and pelvic nerve afferent projections in the same region. They were prominent in the S1-S3 segments but not in adjacent segments (L6-L7 and Cx1) or in thoracolumbar and cervical segments. NADPH-d activity and VIP immunoreactivity in Lissauer's tract and the lateral dorsal horn were eliminated or greatly reduced after dorsal-ventral rhizotomy (S1-S3), indicating the fibers represent primary afferent projections. A population of small diameter afferent neurons in the L7-S2 dorsal root ganglia were intensely stained for NADPH-d. The functional significance of the NADPH-d histochemical stain remains to be determined; however, if NADPH-d is nitric oxide synthase then this would suggest that nitric oxide may function as a transmitter in thoracolumbar sympathetic preganglionic efferent pathways and in sacral parasympathetic afferent pathways in the cat.

Afferent Pathways↗

Dysautonomia with acute sensory motor neuropathy. A new classification of acute autonomic neuropathy.

OBJECTIVES: To characterize the dysautonomia associated with acute sensory motor neuropathy and to discuss the classification of acute autonomic neuropathy. DESIGN: Case series. METHODS: Sympathetic skin response. Local sweat response to acetylcholine. Norepinephrine infusion test and acetylcholinesterase histochemistry of sural nerve biopsy specimens in addition to making conventional analyses of myelinated and unmyelinated fibers. RESULTS: In 12 patients with chronic neuropathy, acetylcholinesterase-positive fiber density and plantar sympathetic skin response size were well correlated, but in the two patients with acute autonomic sensory and motor neuropathy, there were discrepancies, acetylcholinesterase-positive fiber density being well preserved and sympathetic skin responses being absent. Histologic and electrophysiologic results indicated primary demyelination of the myelinated fibers. In contrast, previous studies of acute autonomic sensory and motor neuropathy reported dysfunction of the sympathetic postganglionic fibers and axonopathic change in myelinated fibers, poor recovery from dysautonomia. CONCLUSIONS: Dysautonomia with acute idiopathic neuropathy can be divided into two categories--postganglionic axonopathic and preganglionic demyelinating types of the sympathetic efferent pathways. The recovery from dysautonomia produced by the former lesion is poor, but recovery is better for that produced by the latter lesion.

Acetylcholine↗

Morphological subclasses of lateral olivocochlear terminals? Ultrastructural analysis of inner spiral bundle in cat and guinea pig.

The lateral olivocochlear efferent pathway terminates in vesicle-filled swellings in the inner spiral bundles under inner hair cells (IHCs) and has been suggested to include at least two chemically distinct subclasses (see, e.g., Vetter et al. [1991] Synapse 7:21-43). In the present study, the ultrastructure and peripheral targets of vesicle-filled swellings in the IHC area of the cat and guinea pig cochleas were quantitatively analyzed to determine 1) whether morphological subclasses could be defined based on swelling size or on the density, size or shape of clear and dense-cored vesicles and 2) whether swellings with different postsynaptic targets differed morphologically. In both cat and guinea pig, all swellings contained large, round, clear vesicles and a variable number of dense-core vesicles. Although evidence of clear-cut subclasses was not compelling, the smallest swellings tended to be rich in dense-core and poor in clear vesicles and rarely formed synaptic contacts. Most of the larger swellings, which tended to contain few dense-core vesicles and a rich complement of clear round vesicles, formed synapses with radial afferent fibers. However, there were no morphological differences between swellings contacting afferents originating on the modiolar vs. pillar sides of the IHC (the source of afferents with low and high spontaneous discharge rates, respectively). We conclude that 1) if distinct gamma-amino butyric acid (GABA)ergic and cholinergic subclasses of lateral olivocochlear (LOC) fibers exist, then the vesicle morphology of their terminals does not differ as it does in the central nervous system and that 2) if peptide neurotransmitters, such as calcitonin gene-related peptide and enkephalins, are packaged in dense-core vesicles, then the LOC terminals synapsing with IHC afferent fibers are not particularly rich in these peptides.

Animals↗

Differential distribution of (GABA)A receptor subunits on bulbospinal serotonergic and nonserotonergic neurons of the ventromedial medulla of the rat.

Spinally projecting neurons of the ventromedial medulla (VMM) compose an important efferent pathway for the modulation of nociception. These neurons receive a substantial gamma-aminobutyric acid (GABA)-ergic input, but the GABA receptor that mediates this input is unknown. This study examined the distribution of GABA(A) receptor alpha1 and alpha3 subunits in serotonergic and nonserotonergic neurons of the VMM that project to the dorsal horn in the rat. A pledget of Gelfoam soaked in Fluoro-Gold was placed at the thoracolumbar junction of the spinal cord to label spinally projecting neurons. Alternate sections of the medulla were then incubated with a mixture of antisera to either serotonin and the alpha1 subunit, or to serotonin and the alpha3 subunit of the GABA(A) receptor. Nearly 30% of spinally projecting neurons in the VMM were immunoreactive for the alpha1 subunit. A similar percentage of spinally projecting neurons in the VMM were immunoreactive for the alpha3 subunit, although diffuse cellular labeling combined with intense staining of processes in the neuropil precluded a rigorous semi-quantitative estimation of this population. No alpha1-subunit-immunoreactive neurons colocalized serotonin. In contrast, serotonergic neurons were immunoreactive for the alpha3 subunit. However, these double-labeled neurons were a modest percentage of the serotonergic population. A small percentage of spinally projecting serotonergic neurons was immunoreactive for the alpha3 subunit. These results suggest that significant numbers of spinally projecting serotonergic and nonserotonergic neurons of the VMM possess GABA(A) receptors that differ in their respective subunit compositions and that both classes of neurons may mediate the antinociception produced by the microinjection of GABA(A) receptor antagonists in the VMM.

Animals↗

Nicotinic acetylcholine receptors in rat cochlear nucleus: [125I]-alpha-bungarotoxin receptor autoradiography and in situ hybridization of alpha 7 nAChR subunit mRNA.

The cochlear nucleus (CN) is the first site in the central nervous system (CNS) for processing auditory information. Acetylcholine in the CN is primarily extrinsic and is an important neurotransmitter in efferent pathways thought to provide CNS modulation of afferent signal processing. Although muscarinic acetylcholine receptors have been studied in the CN, the role of nicotinic receptors has not. We examined the distribution of one nicotinic acetylcholine receptor subtype, the alpha-bungarotoxin receptor (alpha Bgt), in the CN. Quantitative autoradiography was used to localize receptors and in situ hybridization was used to localize alpha 7 mRNA in CN neurons that express the alpha Bgt receptor. Binding sites for alpha Bgt are abundant in the anterior ventral, posterior ventral, and dorsal divisions of the CN, and receptor density is low in the granule cell layer and interstitial nucleus. Heterogeneity in CN subregions is described. Four distinct patterns of alpha Bgt binding were observed: (1) binding over and around neuronal cell bodies, (2) receptors locally surrounding neurons, (3) dense punctate binding in the dorsal CN (DCN) not associated with neuronal cell bodies, and (4) diffuse fields of alpha Bgt receptors prominent in the DCN molecular layer, a field underlying the granule cell layer and in the medial sheet. The perikaryial receptors are abundant in the ventral CN (VCN) and are always associated with neurons expressing mRNA for the receptor. Other neurons in the VCN also express alpha 7 mRNA, but without alpha Bgt receptor expression associated with the cell body. In general, alpha Bgt receptor distribution parallels cholinergic terminal distribution, except in granule cell regions rich in cholinergic markers but low in alpha Bgt receptors. The findings indicate that alpha Bgt receptors are widespread in the CN but are selectively localized on somata, proximal dendrites, or distal dendrites depending on the specific CN subregion. The data are consistent with the hypothesis that descending cholinergic fibers modulate afferent auditory signals by regulating intracellular Ca2+ through alpha Bgt receptors.

Animals↗

Role of the Bötzinger complex in fastigial nucleus-mediated respiratory responses.

We have reported that the phrenic neurogram (PN) is modulated by stimulation of the fastigial nucleus (FN) of the cerebellum. The present study was undertaken to search for brainstem site(s) involved in the FN efferent pathway to modulate phrenic nerve activities. Experiments were performed on 35 anesthetized, paralyzed, and ventilated cats, using the PN as the index of the respiratory motor output. Results showed that bilateral electrolytic lesions of the red nucleus (RN), the paramedian reticular nucleus (PRN), or the pontine respiratory group (PRG) had little effect on the ability of FN stimulation to modulate the respiratory output. However, the modulation was abolished by bilateral electrolytic lesions of the Bötzinger complex (BötC). Further studies showed that bilateral chemical inactivation of BötC neurons produced by topical microinjection of kainic acid or cobalt chloride failed to abolish the modulation. We concluded that fibers of passage, not synapses or cell bodies in the BötC, were involved in the modulatory effect of FN stimulation on the PN. The RN, PRN, and PRG appear not to be important in the neural circuitry responsible for the FN modulation of the phrenic activity.

Animals↗

Substantia nigra glutamate antagonists produce contralateral turning and basal ganglia Fos expression: interactions with D1 and D2 dopamine receptor agonists.

Experiments measuring behavior and immediate-early gene expression in the basal ganglia can reveal interactions between dopamine (DA) and glutamate neurotransmission. Nigrostriatal DA projections influence two striatal efferent pathways that, in turn, directly and indirectly influence the activity of the substantia nigra pars reticulata (SNr). This report tests the interactions between striatal DA receptors and nigral glutamate receptors on basal ganglia function by examining both contralateral turning and Fos immunoreactivity in striatum and pallidum following unilateral intranigral microinfusions of glutamate antagonists given to intact and 6-OHDA-lesioned rats. The NMDA antagonist AP5 (1 microg), or the AMPA/kainate antagonist DNQX (0.015-1.5 microg), injected into the SNr (0.5 microl) elicited contralateral turning as well as both striatal and pallidal Fos expression. Moreover, intranigral DNQX elicited more turning and greater numbers of Fos-positive striatal neurons in 6-OHDA-lesioned animals than in unlesioned controls, suggesting that the 6-OHDA injection induces functional changes in nigral glutamate transmission. In 6-OHDA-lesioned rats, systemic injections of the DA D1 receptor agonist SKF38393 (0.5 mg/kg, i.p.) increased striatal Fos expression due to intranigral DNQX. In contrast, the D2 agonist quinpirole (0.1 mg/kg, i.p.) decreased striatal Fos expression but increased the pallidal Fos arising from intranigral AP5. In additional experiments, both intact and 6-OHDA-lesioned rats were given simultaneous intranigral and intrastriatal infusions and turning and pallidal Fos expression were measured. 6-OHDA-lesioned rats given 5 microg of intrastriatal quinpirole exhibited both turning and pallidal Fos that was significantly increased by intranigral AP5. These results indicate that the opposing influences of D2 agonists and endogenous nigral glutamate transmission are mediated by striatal D2 receptors. Finally, the behavioral effects of intranigral glutamate antagonism can be dissociated from the effects on striatal or pallidal immediate-early gene expression.

Animals↗

Monosynaptic projections from the nucleus retroambiguus to motoneurons supplying the abdominal wall, axial, hindlimb, and pelvic floor muscles in the female rhesus monkey.

The nucleus retroambiguus (NRA) consists of premotor neurons in the caudal medulla. It is involved in expiration, vomiting, vocalization, and probably reproductive behavior by means of projections to distinct motoneuronal cell groups. Because no information is available about the NRA and its efferent pathways in primates, the present study examines NRA projections to the lumbosacral spinal cord in female rhesus monkeys. To identify the NRA, wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was injected into the lumbosacral cord in three monkeys. To study the distribution of NRA axons in the lumbosacral cord, WGA-HRP injections were made into the NRA in seven monkeys. To identify motoneuronal cell groups receiving input from the NRA, the same seven monkeys also received cholera toxin subunit b (CTb) injections into different hindlimb, axial, and pelvic floor muscles. The results show that NRA neurons projecting to the lumbosacral cord are mainly located between 1 to 4 mm caudal to the obex. They send numerous axons to external oblique and pelvic floor motoneurons, whereas projections to iliopsoas and axial motoneurons are less numerous. The projections are bilateral, but show a clear contralateral predominance in the iliopsoas, axial, and pelvic floor motoneuronal cell groups. At the ultrastructural level, NRA-terminal profiles make asymmetrical contacts with labeled and unlabeled dendrites in these motoneuronal cell groups and contain large amounts of spherical and a few dense core vesicles. It is concluded that the NRA is well developed in the monkey and that there exists a direct pathway from the NRA to lumbosacral motoneurons in this species. The finding that the NRA projects to a somewhat different set of motoneuronal cell groups compared with other species fits the concept that it is not only involved in expiration-related activities but also in species specific receptive and submissive behavior.

Abdominal Muscles↗

Outer submucous plexus: an intrinsic nerve network involved in both secretory and motility processes in the intestine of large mammals and humans.

The architecture of the enteric nerve networks in the gastrointestinal tract appears to be more complex in large mammals, including humans, than in small laboratory animals. At least two distinct ganglionic nerve plexuses could be identified in the submucous layer in the digestive tract of large mammals. While functionally and morphologically similar neuron populations are found in the intestinal wall of both small and large mammals, significant differences in their topographical organization and neurochemical features may be present. This short review clearly illustrates that the close and exclusive association, which has been assumed so far between the efferent pathways of the submucous plexus and regulation of intestinal secretion/absorption on the one hand and between the myenteric plexus and regulation of intestinal motility on the other hand, cannot be interpreted that strictly. An attempt has been made to give a briefoverview of the current status of the identification of distinct functional enteric neuronal classes in the gastrointestinal tract of large mammals using the pig and human intestine as references, and to compare these data with the more extensive information gathered from the guinea-pig intestine.

Animals↗

Hypometric saccades and low-gain pursuit resulting from a thalamic hemorrhage.

Saccadic and pursuit eye movements were measured in a patient with a right thalamic hemorrhage using an infrared reflection technique. Saccades were hypometric when directed away from the side of the lesion, and pursuit was low in gain, with many interposed saccades, when directed toward the side of the lesion. This eye movement pattern is similar to that observed in hemidecorticate patients. We postulate that the ocular abnormalities observed in our patients were secondary to an interruption of the efferent pathways from the right cerebral areas mediating saccadic and smooth-pursuit eye movements.

Eye Movements↗