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Maturation of postsynaptic nicotinic structures on autonomic neurons requires innervation but not cholinergic transmission.

Postsynaptic development at the neuromuscular junction depends on nicotinic transmission and secreted components from the presynaptic motor nerve terminal. Similarly, secreted components and synaptic activity are both thought to guide development of glutamatergic synapses in the CNS. Nicotinic synapses on chick ciliary neurons are structurally complex: a large presynaptic calyx engulfs the postsynaptic neuron and overlays a series of discrete mats of receptor-rich somatic spines tightly interwoven and folded against the soma. We used fluorescence imaging of alpha 7-containing nicotinic receptors and the spine constituent drebrin to monitor postsynaptic development. The results show that surgical disruption of the preganglionic input or removal of the ganglionic synaptic target tissue after synapses form in the ganglion does not disrupt the receptor-rich spine mats. Similarly, removal of the target tissue even prior to synapse formation in the ganglion does not prevent subsequent formation of the receptor clusters and associated spine constituents. Postsynaptic development is arrested, however, if normal innervation is prevented by ablating the preganglionic neurons prior to synapse formation. In this case the neurons express reduced levels of nicotinic receptors and cytoskeletal components and organize them only into early-stage clusters. Even low levels of residual innervation, however, can restore much of the normal postsynaptic receptor patterns. Chronic pharmacological blockade of cholinergic synaptic activity fails to replicate the effects of ablating the preganglionic nucleus. The results indicate that ciliary neurons are programmed to express postsynaptic components and can initiate clustering of alpha 7-containing receptors but need presynaptic guidance for maturation of the postsynaptic structure.

Acetylcholine↗

Synapses involving auditory nerve fibers in primate cochlea.

The anatomical mechanisms for processing auditory signals are extremely complex and incompletely understood, despite major advances already made with the use of electron microscopy. A major enigma, for example, is the presence in the mammalian cochlea of a double hair cell receptor system. A renewed attempt to discover evidence of synaptic coupling between the two systems in the primate cochlea, postulated from physiological studies, has failed. However, in the outer spiral bundle the narrow and rigid clefts seen between pairs of presumptive afferent fibers suggest the possibility of dendro-dendritic interaction confined to the outer hair cell system. The clustering of afferent processes within folds of supporting cells subjacent to outer hair cells is in contrast to the lack of such close associations in the inner hair cell region. The difference reinforces the suggestion of functional interaction of some sort between the outer hair cell afferent nerve processes.

Afferent Pathways↗

The pattern of monosynaptic Ia-connections to hindlimb motor nuclei in the baboon: a comparison with the cat.

The pattern of Ia-connections to motor nuclei of 17 hindlimb muscles (or groups of muscles) has been investigated in baboons by intracellular recording of Ia-e.ps.p.s evoked in motoneurons from different muscle nerves. The amplitudes are normalized to 70 mV resting potential and compared with similarly normalized Ia-e.ps.p.s in cats. As in the cat, Ia-excitation is drawn from a restricted number of muscles and the homonymous effect is usually dominating. Heteronymous connections to many motor nuclei are different in the two species. For example, hip extensors are generally more Ia-isolated from each other in baboons than in cats, and also knee flexors have fewer Ia-interconnections than in cats. A unidirectional Ia-synergism between some hip extensors and knee flexors in cats has changed to a bidirectional one in baboons, with a tendency to lateralization of the connections. Among ankle extensors, soleus has smaller heteronymous Ia-connections from its synergic ankle extensors than in cats. In baboons, plantaris is heteronymously Ia-excited from gastrocnemius-soleus but not from the intrinsic plantar muscles; whereas in cats there exists a considerable Ia-projection from the intrinsic plantar muscles but not from gastrocnemius-soleus. There is a corresponding difference in the insertion of the plantaris tendon, which shows that this muscle acts as toe extensor in cats but as ankle extensor in baboons. For most of the motor nuclei, the homonymous as well as the total aggregate of Ia-e.ps.p.s is smaller in the baboon than in the cat; but the amplitude range between different motor nuclei is larger in the baboon. Reciprocal Ia-i.ps.p.s are evoked only after spinal transection or when brain function is depressed. It is postulated that baboons, contrary to cats, have descending tonic inhibition of transmission in the reciprocal Ia-inhibitory pathway. The phylogenetic flexibility of Ia-connections is discussed and contrasted with their ontogenetic stability.

Action Potentials↗

The distribution of static gamma-axons in the tenuissimus muscle of the cat.

1. The distribution of static gamma-axons within and among muscle spindles of the tenuissimus muscle has been studied in the anaesthetized cat, on the basis of the effects on the responses of primary endings when bag2 or chain fibres or both are activated by static gamma-stimulation. 2. Locations of spindles were marked for subsequent histological analysis using teased, silver-impregnated preparations. 3. Static effects were classified into: (i) biassing; (ii) driving; or (iii) indeterminate categories. 4. Critical correlations established that the biassing type was produced by bag2 activity, either alone or in combination with chain fibres, whereas the driving type was produced by chain fibres active alone. Indirect evidence suggested that indeterminate effects were produced by bag2 and chain fibres active together. 5. The static gamma-axons showed some differential distribution according to their conduction velocities: faster-conducting axons were likely to be more widely distributed among spindles but less likely to innervate chain fibres alone than were more slowly conducting axons. 6. The results are discussed in terms of their possible functional and developmental significance.

Afferent Pathways↗

Effect of liver denervation on the feeding pattern of rats.

This study was undertaken to assess the role of the hepatic innervation in the short-term regulatory mechanisms of food intake. A liver denervation was performed in male Wistar rats: the liver was entirely freed from the surrounding organs, its vessels (with the exception of the hepatic veins) and the bile ducts were stripped. Controls consisted of two groups of liver-denervated rats in which sympathectomy or vagotomy were carried out. A continuous recording of food intake was performed in a third group. The complete absence of the hyperglycemic response to trauma in adrenalectomized liver-denervated animals was taken as evidence of functional sympathectomy of the liver. The disappearance of a vagovagal reflex--heart rate variation brought about by a glucose injection into the portal vein--was taken as evidence of functional vagotomy. The analysis of the recorded feeding patterns of liver-denervated and sham-operated animals showed that, in rats, this liver denervation did not affect in any way the feeding behavior.

Afferent Pathways↗

Morphology and physiology of the cerebellar vestibulolateral lobe pathways linked to oculomotor function in the goldfish.

Intracellular recording and single-cell labeling were combined to investigate the oculomotor circuitry of the goldfish cerebellar vestibulolateral lobe, consisting of the eminentia granularis (Egr) and caudal lobe. Purkinje cells exhibiting highly conserved vertebrate electrophysiological and morphological properties provide the direct output from the caudal lobe to the vestibular nuclei. Biocytin labeling of the Egr distinguished numerous hindbrain precerebellar sources that could be divided into either putative mechano- or vestibulosensitive nuclei based on cellular location and axon trajectories. Precerebellar neurons in a hindbrain nucleus, called Area II, were electrophysiologically characterized after antidromic activation from the Egr (>50% bilateral) and their morphology analyzed after intracellular biocytin labeling (n = 28). Bipolar spindle-shaped somas ranged widely in size with comparably scaled dendritic arbors exhibiting largely closed field configuration. Area II neurons (85%) projected to the ipsilateral Egr with most (93%) sending a collateral through the cerebellar commissure to the contralateral Egr; however, 15% projected to the contralateral Egr by crossing in the ventral hindbrain. Axon terminals in the vestibular nucleus were the only collaterals within the hindbrain. Every Area II neuron received a disynaptic EPSP after contralateral horizontal canal nerve stimulation and a disynaptic IPSP, preceded by a small EPSP (>50%), after ipsilateral activation. Vestibular synaptic potentials were of varying shape/amplitude, unrelated to neuron location in the nucleus, and thus likely a correlate of somadendritic size. The exceptional separation of eye position and eye velocity signals into two separate hindbrain nuclei represents an ideal model for understanding the precerebellar projection to the vestibulocerebellum.

Afferent Pathways↗

Presynaptic dopamine D1 receptors attenuate excitatory and inhibitory limbic inputs to the shell region of the rat nucleus accumbens studied in vitro.

1. Intracellular recordings were made from the shell region of the nucleus accumbens in an in vitro slice preparation. The mean resting membrane potential, input resistance, and action potential amplitude of these neurons were -76 +/- 1 mV, 87 +/- 5 M omega and 94 +/- 2 mV (N = 108), respectively. A sample of these neurons (N = 18) was identified as medium spiny neurons with the use of the biocytin-avidin labeling technique. 2. Electrical stimulation of the fornix, subcortical fibers, or neuropil within the nucleus accumbens shell itself elicited a depolarizing postsynaptic potential (PSP). Dopamine (10-100 microM) attenuated PSPs elicited by stimulation of all of these sites. In a paired-pulse stimulation protocol, dopamine was observed to enhance the facilitation of the test response with respect to the conditioning response. 3. The suppressive effect of dopamine was mimicked by the D1 receptor agonist SKF 82958 (10-30 microM), whereas the D2 receptor agonist quinpirole (10-30 microM) was ineffective. The action of dopamine was antagonized by the D1 receptor antagonist Sch 23390 (10-30 microM), but not by the D2 receptor antagonist sulpiride (10-50 microM) or various adrenergic receptor antagonists. 4. The PSP was usually composed of an excitatory postsynaptic potential (EPSP)-inhibitory postsynaptic potential (IPSP) sequence. Dopamine equally attenuated the excitatory and inhibitory component of the synaptic response. The attenuation of both EPSP and IPSP did not depend on membrane potential. 5. Dopamine effects on the resting membrane potential and input resistance were variable and did not correlate with changes in the PSP. Two further indications were found in favor of a presynaptic locus of dopaminergic modulation. First, the time course of the PSP was not altered during dopamine application. Second, dopamine did not attenuate depolarizations induced by bath-applied L-glutamate. In extracellular recordings, it was found that dopamine reduced the population spike but not the presynaptic fiber volley. 6. These findings strongly indicate that dopaminergic modulation of synaptic responses in neurons located in the accumbens shell region is mediated by presynaptic D1 receptors. Notably, dopamine does not exert a purely inhibitory effect on synaptic excitability in the nucleus accumbens, because it suppresses both the excitatory and inhibitory component of the synaptic response.

Afferent Pathways↗

Sensorimotor state of the contralateral leg affects ipsilateral muscle coordination of pedaling.

The objective of this study was to determine if independent central pattern generating elements controlling the legs in bipedal and unipedal locomotion is a viable theory for locomotor propulsion in humans. Coordinative coupling of the limbs could then be accomplished through mechanical interactions and ipsilateral feedback control rather than through central interlimb neural pathways. Pedaling was chosen as the locomotor task to study because interlimb mechanics can be significantly altered, as pedaling can be executed with the use of either one leg or two legs (cf. walking) and because the load on the limb can be well-controlled. Subjects pedaled a modified bicycle ergometer in a two-legged (bilateral) and a one-legged (unilateral) pedaling condition. The loading on the leg during unilateral pedaling was designed to be identical to the loading experienced by the leg during bilateral pedaling. This loading was achieved by having a trained human "motor" pedal along with the subject and exert on the opposite crank the torque that the subject's contralateral leg generated in bilateral pedaling. The human "motor" was successful at reproducing each subject's one-leg crank torque. The shape of the motor's torque trajectory was similar to that of subjects, and the amount of work done during extension and flexion was not significantly different. Thus the same muscle coordination pattern would allow subjects to pedal successfully in both the bilateral and unilateral conditions, and the afferent signals from the pedaling leg could be the same for both conditions. Although the overall work done by each leg did not change, an 86% decrease in retarding (negative) crank torque during limb flexion was measured in all 11 subjects during the unilateral condition. This corresponded to an increase in integrated electromyography of tibialis anterior (70%), rectus femoris (43%), and biceps femoris (59%) during flexion. Even given visual torque feedback in the unilateral condition, subjects still showed a 33% decrease in negative torque during flexion. These results are consistent with the existence of an inhibitory pathway from elements controlling extension onto contralateral flexion elements, with the pathway operating during two-legged pedaling but not during one-legged pedaling, in which case flexor activity increases. However, this centrally mediated coupling can be overcome with practice, as the human "motor" was able to effectively match the bilateral crank torque after a longer practice regimen. We conclude that the sensorimotor control of a unipedal task is affected by interlimb neural pathways. Thus a task performed unilaterally is not performed with the same muscle coordination utilized in a bipedal condition, even if such coordination would be equally effective in the execution of the unilateral task.

Adult↗

Bilateral reflex vasodilation in the palatal mucosa evoked by unilateral tooth-pulp stimulation in the cat.

In a previous study in cats, we found that electrical stimulation of the tooth pulp caused blood flow increases at various sites in the ipsilateral oral mucosa (upper and lower gingivae, lower lip, buccal mucosa and tongue, and, notably, bilaterally in the palatal mucosa). Tooth-pulp stimulation is well-known to induce severe pain and to evoke autonomic reflex responses in other organs and tissues. The purpose of this study was: to confirm that tooth-pulp stimulation may indeed induce autonomically mediated vasodilator responses in the feline oral mucosa away from the stimulated tooth, and to test our hypothesis that the reflex pathway involves parasympathetic vasodilator fibers as efferents. Dynamic changes in palatal mucosal blood flow (PMBF), with lower lip blood flow (LBF) as a control, were investigated in anesthetized, cervically sympathectomized cats by means of Laser Doppler Flowmetry. Unilateral electrical stimulation of the maxillary canine tooth pulp produced hexamethonium-sensitive bilateral increases in PMBF in a stimulus-intensity-dependent manner, without an increase in systemic blood pressure; LBF increased only ipsilaterally. Bilateral section of the glossopharyngeal nerve roots had no effect on the vasodilator responses, while unilateral section of the facial nerve root or lesion of the pterygopalatine ganglion (PPG) abolished the response on that side. Intracranial electrical stimulation of the peripheral cut ends of the facial or glossopharyngeal nerve roots caused an increase in ipsilateral PMBF. These results indicate that unilateral tooth-pulp stimulation induces a bilateral reflex vasodilator response in the palatal mucosa mediated via parasympathetic vasodilator fibers that emerge from the brain stem with the facial nerve and reach the blood vessels via PPG. Although there is a dual innervation of the cat palatal mucosa by parasympathetic vasodilator fibers running via the facial and glossopharyngeal nerve roots, the latter are not involved in the bilateral reflex responses.

Animals↗

Lateral olivocochlear neurons contain both enkephalin and dynorphin immunoreactivities: immunocytochemical co-localization studies.

Antibodies to methionine enkephalin and to dynorphin B were used in an immunocytochemical study examining co-containment of enkephalins and dynorphins in olivocochlear neurons in the guinea pig lateral superior olive. Two methods of sequential co-localization were employed: one using primary antibodies from different species, the second using elution of antibodies. Co-localization of enkephalin-like and dynorphin-like immunoreactivities was found in lateral olivocochlear neurons, suggesting co-containment of enkephalins and dynorphins in this projection pathway from the lateral superior olive to the organ of Corti.

Animals↗

Spreading of sudomotor axon reflexes in human skin.

BACKGROUND: Acetylcholine (ACh) activates both sudomotor fibers and primary afferent nociceptors. This leads to sudomotor and vasodilator axon reflexes, which can be diminished, for example, in neuropathies. In some neuropathies, however, there is increased axon reflex sweating, a response pattern that has never been observed for vasodilator flares. OBJECTIVES: To compare both types of axon reflexes and to elucidate possible differences. METHODS: In healthy young male subjects, sweat response and flare reaction in response to ACh were quantified. Constant-current iontophoresis (300 mC) of ACh was performed on the lateral lower legs. The sudomotor axon reflex was visualized with iodine starch staining, and the sweat response was quantified with capacitance hygrometry (quantitative sudomotor axon reflex test [QSART]). The vasodilator flare was visualized and quantified by laser Doppler imaging. All measurements were performed during and for 10 minutes after finishing the iontophoresis. RESULTS: The sudomotor axon reflex area increased from 30.6 cm2 at the end of the iontophoresis to 39.2 cm2 (p < 0.001) 10 minutes later, while QSART response had already decreased. Flare size and flare intensity remained nearly constant during the observation period. CONCLUSION: Despite fast cleavage of acetylcholine by cholinesterases, sudomotor axon reflexes spread in the skin, indicating a possible peripheral amplification of sweating.

Acetylcholine↗

Toward an agreement on terminology of nuclear and subnuclear divisions of the motor thalamus.

The nomenclature most commonly applied to the motor-related nuclei of the human thalamus differs substantially from that applied to the thalamus of other primates, from which most knowledge of input-output connections is derived. Knowledge of these connections in the human is a prerequisite for stereotactic neurosurgical approaches designed to alleviate movement disorders by the placement of lesions in specific nuclei. Transfer to humans of connectional information derived from experimental studies in nonhuman primates requires agreement about the equivalence of nuclei in the different species, and dialogue between experimentalists and neurosurgeons would be facilitated by the use of a common nomenclature. In this review, the authors compare the different nomenclatures and review the cyto- and chemoarchitecture of the nuclei in the anterolateral aspect of the ventral nuclear mass in humans and monkeys, suggest which nuclei are equivalent, and propose a common terminology. On this basis, it is possible to identify the nuclei of the human motor thalamus that transfer information from the substantia nigra, globus pallidus, cerebellum, and proprioceptive components of the medial lemniscus to prefrontal, premotor, motor, and somatosensory areas of the cerebral cortex. It also becomes possible to suggest the principal functional systems involved in stereotactically guided thalamotomies and the functional basis of the symptoms observed following ischemic lesions in different parts of the human thalamus.

Afferent Pathways↗

An inhibitory interface gates impulse traffic between the input and output stations of the amygdala.

The central amygdaloid nucleus projects to brainstem and hypothalamic nuclei mediating fear responses and receives convergent sensory inputs from the basolateral amygdaloid complex. However, interposed between the basolateral complex and central nucleus is a string of interconnected GABAergic cell clusters, the intercalated cell masses. Here, we analyzed how intercalated neurons influence impulse traffic between the basolateral complex and central nucleus using whole-cell recordings, microstimulation, and local application of glutamate receptor antagonists in brain slices. Our results suggest that intercalated neurons receive glutamatergic inputs from the basolateral complex and generate feedforward inhibition in neurons of the central nucleus. As the position of the recording site was shifted medially, intercalated cells projected to gradually more medial sectors of the central nucleus and were maximally responsive to progressively more medial stimulation sites in the basolateral complex. Thus, there is a lateromedial correspondence between the position of intercalated cells, their projection site in the central nucleus, and the source of their excitatory afferents in the basolateral complex. In addition, basolateral stimulation sites eliciting maximal excitatory responses in intercalated neurons were flanked laterally by sites eliciting prevalently inhibitory responses via the activation of intercalated cells located more laterally. As a result, the feedforward inhibition generated by intercalated neurons and, indirectly, the amplitude of the responses of central neurons could be increased or decreased depending on which combination of amygdala nuclei are activated and in what sequence. Thus, the output of the central nucleus depends not only on the nature and intensity of sensory inputs but also on their timing and origin.

Afferent Pathways↗

Input-output relations of Deiters' lateral vestibulospinal neurons with different structures of the brain.

It has been the goal of this review to describe the functional interrelations between Deiters' vestibular nucleus and numerous brain structures. Emphasis is placed on dynamic and integrative properties of linkages between the neurons of Deiters' nucleus and many other brain structures in order to begin considering the capabilities of the loops in the light of motor control and coordination of movement. The problem of somatotopy within the loops is also considered. Putting this information together, the possible roles of Deiters' nucleus in the control of movements are described. It is suggested that Deiters' nucleus in co-operation with cerebral cortex, cerebellum, subcortical and brainstem structures are responsible for the integration and realization of different movements.

Afferent Pathways↗

Comparative aspects of basal forebrain organization in vertebrates.

The present survey shows that basal ganglia organization in the three classes of amniotes has many features in common. Yet, there are several differences that are important to note since they contribute to a better understanding of the evolution of those brain structures. They also underscore once again that it is questionable to generalize the results obtained in a certain species. This question is the more important in view of the general practice in mammalian research. Comparative studies may be of great help to solve this problem. The reported differences in acetylcholine release after pharmacological treatment in the striatum of rats and reptiles have stimulated further research that has led to the conclusion that the nucleus accumbens in the rat is a very heterogeneous structure with respect to the regulation of the release of acetylcholine by D2 dopamine and NMDA receptor activation. In this regard, the striatum of reptiles may offer a model for studying the functioning of the caudomedial part of the rat nucleus accumbens.

Acetylcholine↗