Synaptic efficacy of inhibitory synapses in the reinnervating hypoglossal motoneurons.

The synaptic efficacy of inhibitory synapses in tongue protruder motoneurons reinnervating the tongue retractor muscle was studied in cats. We have demonstrated that the percentage magnitude of a short- and a long-lasting inhibitory postsynaptic potential in the inhibitory postsynaptic potentials produced in the tongue protruder motoneurons, whose axons had been cut but allowed to regenerate to make functional contact with the tongue retractor muscles, by lingual nerve or inferior alveolar nerve stimulation, was rearranged to appear like that exhibited by the tongue retractor motoneurons that normally supply that muscle. In addition, the peak amplitude of the summated afterhyperpolarization in a tongue protruder motoneuron on operated cats at nine months axon-union was in the normal range.     

Cortically induced postsynaptic potentials in hypoglossal motoneurons after axotomy

Cortically induced postsynaptic potentials were studied in normal and axotomized cat hypoglossal motoneurons. In normal protruder motoneurons innervating tongue protruder muscles, we have demonstrated that stimulation of the orbital gyrus, at the point optimum for inducing lapping movements of the tongue by repetitive stimuli, produced inhibitory postsynaptic potentials or excitatory postsynaptic potentials followed by predominant inhibitory postsynaptic potentials. The cortically induced excitatory postsynaptic potential in normal protruder motoneurons was composed of only the short-latency component. In protruder motoneurons 30, 40, 60 and 80 days after axotomy, we have demonstrated that the number of protruder motoneurons responding with two components of excitatory postsynaptic potentials (the short- and the long-latency component) to cortical stimulation increased in correspondence with the lapse of days after axotomy and that the amplitude of cortically induced inhibitory postsynaptic potentials in axotomized protruder motoneurons was reduced in size as compared with normal protruder motoneurons.     

Synaptic efficacy of inhibitory synapses and repetitive firing in the reinnervating trigeminal and hypoglossal motoneurons

The synaptic efficacy and repetitive firing in masseteric motoneurons after the self-union operation and in tongue protruder motoneurons after their cut axons were reunited to tongue retractor muscles, the styloglossus muscle, were studied in cats. To ensure the correct identification of reinnervating motoneurons, the muscle response produce by an induced spike in a motoneuron by intracellularly injected depolarizing current was recorded. In both masseteric and tongue protruder motoneurons there were no differences on the patterns of postsynaptic potentials produced in reinnervating and non-reinnervating motoneurons by peripheral nerve stimulation, suggesting that the recovery of the synaptic efficacy of inhibitory synapses is time-dependent rather than muscle reinnervation. However, the present study demonstrated that the recovery of processes that control rhythmical firing of motoneurons is probably dependent on muscle reinnervation.     

Cortically and lingually induced postsynaptic potentials in trigeminal motoneurons after axotomy

Summary The membrane properties and the efficacy of excitatory and inhibitory synapses were studied in cat masseteric motoneurons (Mass Mns) after axotomy. In axotomized Mass Mns the slope of the primary range in the frequency-current relationship showed a higher gain than that of normal Mass Mns. The safety of antidromic invasion was increased and the initial segment component of antidromic action potentials could not be separated from the somadendritic component. In normal Mass Mns a single shock delivered to the orbital gyrus or the lingual nerve induced long-lasting inhibitory postsynaptic potentials (IPSPs). In two-thirds of Mass Mns explored 30 days after axotomy, a single shock delivered to the orbital gyrus or the lingual nerve evoked a mixture of inhibitory and excitatory synaptic potentials. In Mass Mns 50 days after axotomy, we have demonstrated that the major fraction of the total sample of explored Mass Mns showed long-lasting excitatory postsynaptic potentials followed by IPSPs. The results suggest that in Mass Mns, axotomy is followed by the decline of synaptic efficacy of inhibitory rather than of excitatory synapses.     

Corticofugal inhibitory effects on lingually induced postsynaptic potentials in cat hypoglossal motoneurons

The suppression of lingually or cortically induced postsynaptic potentials produced by conditioning stimulation of the cerebral cortex or the lingual nerve was studied in cat hypoglossal motoneurons. We have demonstrated that lingually or cortically induced inhibitory postsynaptic potentials were effectively suppressed by a conditioning stimulus of the cerebral cortex or the lingual nerve. In hypoglossal motoneurons after blocking inhibitory postsynaptic potentials by the administration of strychnine, lingually induced excitatory postsynaptic potentials and spikes were effectively suppressed by cortical stimulation. Whereas, a conditioning stimulus of the lingual nerve suppressed only a long-latency excitatory postsynaptic potential evoked by a test stimulus of the cerebral cortex, while a short-latency excitatory postsynaptic potential was unaffected. Picrotoxin and bicuculline appeared to act by reducing the suppression of lingually induced excitatory postsynaptic potentials produced by cortical conditioning stimulation.     

The excitability of hypoglossal motoneurons undergoing chromatolysis

In chromatolysed hypoglossal motoneurons impulse transmission from the initial segment to the soma-dendritic membrane, the relationship of firing frequency to stimulating current, and the trajectory of antidromic responses were explored. In some axotomized motoneurons by the 7th post-operative day the initial segment component could not be separated from the soma-dendritic component. No significant changes were observed on inhibitory postsynaptic potentials produced by lingual nerve stimulation in comparison with normal motoneurons. The slope of the primary range showed a high gain in relation to stimulating current in axotomized motoneurons 14 days after axotomy. On the 28th post-operative day most axotomized motoneurons produced a large delayed depolarization following an antidromic spike.From these findings it is suggested that hypoglossal motoneurons undergoing chromatolysis have a high safety factor for impulse transmission from the initial segment component to the soma-dendritic component and a low threshold for the generation of a spike in the soma-dendritic membrane.     

Excitatory and inhibitory postsynaptic potentials in cat hypoglossal motoneurons during swallowing

Summary The postsynaptic potentials produced in cat genioglossus and styloglossus motoneurons (GG- and SG-Mns) during swallowing were studied. During swallowing elicited by placing water on the dorsum of the tongue, the GG-muscle discharged for 80–210 ms (mean±S. D. 123±31 ms, N=59) and was abruptly suppressed, and the SG-muscle began discharging in synchrony with the GG-muscle and discharged for 200–360 ms (mean+ S. D. 247±36 ms, N=59). The GG and the SG-Mns were identified if unitary muscle activity followed the induced spike of the motoneuron one-for-one. During swallowing, excitatory postsynaptic potentials (EPSPs) were evoked in the SG-Mns regardless of the respiratory drive on the SG-Mns, and inhibitory postsynaptic potential (IPSP) or EPSP-IPSP was evoked on the GG-Mns regardless of the respiratory drive on the GG-Mns. By increasing the intracellular concentration of chloride ions, the IPSP elicited in the GG-Mn during swallowing was turned into a depolarizing potential. In immobilized cats, a depolarizing potential and a depolarizing-hyperpolarizing potential sequence was evoked successively on a tongue retractor motoneuron and a tongue protruder motoneuron by repetitive electrical stimulation of the superior laryngeal nerve.     

Postsynaptic potentials in the hypoglossal motoneurons set up by hypoglossal nerve stimulation.

In nembutalized cats intracellular potentials were recorded from hypoglossal motoneurons innervating either protruder or retractor muscles of the tonge (protruder and retractor motoneurons: P-Mns and R-Mns). Responses to stimulation of the hypoglossal nerve were explored and found to consist of an antidromic spike followed by an afterhyperpolarization (AHP) and a postsynaptic potential (PSP). When hypoglossal nerve stimulation was made with an intensity three times as large as the threshold for the hypoglossal motor fibers, the PSPs became evident under blockage of soma-dendritic invasion of the antidromic spike. In most of P-Mns or R-Mns, the PSPs were IPSPs, independent of the side of peripheral stimulation. The latencies were about 12 msec. Even when the cell membrane was hyperpolarized by injecting a hyperpolarizing current of up to 16 nA, the reversal point of the IPSP was difficult to find. In a small fraction of hypoglossal motoneurons the PSPs to hypoglossal nerve stimulation were EPSPs with latencies of 10 to 12 msec.     

Early and transient increase in spontaneous synaptic inputs to the rat facial motoneurons after axotomy in isolated brainstem slices of rats

Section of motor nerve fibers (axotomy) elicits a variety of morphofunctional responses in the motoneurons in the motor nuclei. Later than the fifth post-operational day after section of the facial nerve, synapse elimination occurs in the facial motoneuron pool, leading to gradual abolishment of synaptic input-driven activities of the axotomized motoneurons. However, it remains unknown how the amount of synaptic input changes during this period between the axotomy and the synaptic elimination. Here we examined a hypothesis that axotomy of the motoneurons itself modifies the synaptic inputs to the motoneurons. One day after axotomy, the postsynaptic currents, mostly mediated by non-N-methyl-D-aspartic acid (non-NMDA) receptors, recorded from the axotomized facial motoneurons in the acute slice preparations of the rats were of higher frequency and larger amplitude than those in the intact motoneurons. This difference was not observed after the third post-operational day and appeared earlier than the changes in the electrophysiological properties and increase in the number of dead neurons in the axotomized motor nucleus. The larger postsynaptic current frequency of the axotomized motoneurons was observed both in the absence and in the presence of tetrodotoxin citrate, suggesting that increased excitability and facilitated release underlie the postsynaptic current frequency increase. These results suggest that synaptic re-organization occurs in the synapses of motoneurons at an early stage following axotomy.     

Inhibition of hypoglossal motoneurons by stimulation of the jaw-opening muscle afferents.

The synaptic linkage of jaw-opening muscle afferents with the retractive and the protrusive motoneurons (R-Mns and P-Mns) in the hypoglossal motor nucleus was explored in anesthetized cats. It was found that stimulation of low-threshold afferents arising in the jaw-opening muscles (m. mylohyoideus and m. digastricus) evoked IPSPs in both R-Mns and P-Mns with about 10 to 15 msec latencies. By injecting Cl ions into R-Mns or P-Mns, the hyperpolarizing postsynaptic potentials evoked by jaw-opening muscle afferent impulses were reversed to depolarizing potentials. The lingual-IPSPs of hypoglossal motoneurons were concluded to be dependent on increase of Cl conductance. Stimulation of low threshold lingual afferents evoked a reflex discharge in the retractive nerve fibers with a 6.0 msec latency and in the protrusive nerve fibers with a 5.5 msec latency. Inhibition of the linguohypoglossal reflex by stimulation of the jaw-opening muscle afferents was completely removed by an intravenous injection of strychnine (0.1 mg/kg) or picrotoxin (6 mg/kg). It is concluded that the low threshold afferents arising in the jaw-opening muscles are connected to both R-Mns and P-Mns and P-Mns through inhibitory synapses via a polysynaptic pathway.     

Genioglossal hypoglossal motoneurons contact substance P-like immunoreactive nerve terminals in the cat: a dual labeling electron microscopic study

This study investigated the synaptic interactions between hypoglossal motoneurons that project to the genioglossus muscle and substance P (SP) containing immunoreactive nerve terminals. Cholera toxin B conjugated to horseradish peroxidase (CTB-HRP) was injected into the right half of the genioglossus muscle in four anesthetized cats. Two days later, the animals were perfused with acrolein fixative. Tetramethylbenzidine (TMB) was the chromogen used to detect retrogradely labeled cells containing CTB-HRP. The tissues were then processed for immunocytochemisty using an antiserum raised against SP with diaminobenzidine (DAB) as the chromogen. At the light microscopic level, labeled cells were observed primarily ipsilaterally in ventral and ventrolateral subdivisions of the hypoglossal nucleus. The majority of these labeled cells were observed at the level of the area postrema. At the electron microscopic level, SP-like immunoreactive nerve terminals formed synaptic contacts with retrogradely labeled dendrites and perikarya. Nineteen percent of the terminals that contacted retrogradely labeled cells contained SP. These are the first ultrastructural studies demonstrating synaptic interactions between protruder hypoglossal motoneurons and SP terminals. These studies demonstrate that hypoglossal motoneurons which innervate the major protruder muscle of the tongue, the genioglossus muscle, may be modulated by SP. Thus, SP may play a role in the control of protrusive movements of the tongue acting via neurokinin receptors.     

Inhibition of styloglossus motoneurons during the palatally induced jaw-closing reflex.

The inhibition of hypoglossal motoneurons innervating the styloglossus muscle during transient jaw closing, the so-called jaw-closing reflex, was studied in cats. The application of diffuse pressure stimulation to the posterior palatal surface produced the jaw-closing reflex and inhibitory postsynaptic potentials in the styloglossus motoneurons, indicating that mechanosensory inputs from the posterior palatal mucosa sent inhibitory synaptic inputs to styloglossus motoneurons. We also demonstrated that, during the palatally induced jaw-closing reflex, the tongue extended at jaw closure and was still extended forward in the initial part of the opening phase. In all of 22 styloglossus motoneurons studied, the depression of firing was elicited after the onset of jaw closure. In 14 of 22 styloglossus motoneurons, the depression of firing was elicited in the closing phase, and in the remaining cells it was elicited in the occlusal phase. By increasing the intracellular concentration of chloride ions, the inhibitory postsynaptic potential elicited in the styloglossus motoneuron converted to a depolarizing potential. It is concluded that the inhibition of styloglossus motoneurons may be involved in the maintenance of tongue protrusions during the palatally induced jaw-closing reflex, and that inhibitory postsynaptic potentials evoked in the styloglossus motoneurons are partly due to a chloride-dependent inhibitory postsynaptic potential.     

Ultrastructural demonstration of adenylate cyclase activity in the rat neostriatum.

The ultrastructural histochemical localization of adenylate cyclase activity in the rat neostriatum was studied using cobalt as a precipitating agent. Basal adenylate cyclase activity was found intracellularly in some dendrites, whereas the neuronal cell bodies and glial cells were negative. In vitro stimulation of the tissue slices with dopamine before the histochemical procedure increased the adenylate cyclase activity which was also found associated with the postsynaptic membranes of axodendritic and axo-spinous synapses mainly containing small empty vesicles. Activity was also seen intracellularly in some nerve terminals containing synaptic vesicles.The significance of the cytochemical localization of dopamine-stimulated adenylate cyclase and the possible morphology of the dopaminergic synapses, including their possible interconnections, are discussed.     

Enhancement of Ia synaptic transmission following muscle nerve section: dependence upon protein synthesis

Monosynaptic excitatory postsynaptic potentials (EPSPs) were recorded from the triceps surae motoneurons in the rat. Two to 3 weeks after section of the medial gastrocnemius (MG) nerve, Ia EPSPs evoked by stimulation of the MG nerve were significantly depressed, as reported previously. However, the MG EPSP amplitude significantly increased within 24 h, reaching a maximum on the 3rd day after axotomy. This increase was prevented by actinomycin-D treatment, indicating that the synaptic enhancement is dependent upon protein synthesis. When disuse of sensory fibers was induced without injuring the muscle nerve, the degree of synaptic enhancement was similar to that after axotomy. Therefore, the enhancement of central synaptic transmission shortly after axotomy is due to the loss of electrical activity, but not due to the axon reaction of the Ia sensory neurons to injury. It is postulated that the presence of some factor in Ia sensory fibers enhances synaptic transmission, while electrical activity of the neurons antagonizes the action of this factor.     

Ultrastructural data,with special reference to bouton/glial relationships,from the hypoglossal nucleus after a second axotomy of the hypoglossal nerve

Summary The left hypoglossal nerve of adult male albino rats was prevented from regenerating to the tongue after a distal axotomy by implanting the proximal stump into normally innervated left sternomastoid muscle. Eighty-four days after implantation, the hypoglossal nerve was transected again and its regeneration to the tongue unimpeded. From 8 to 70 days after this second axotomy the left hypoglossal nuclei were processed for quantitative ultrastructural analysis. The first aim of this study was to compare regeneration success in the hypoglossal nucleus after second axotomy with that accompanying outgrowth of the hypoglossal nerve into denervated sternomastoid muscle. During quantitative analysis a second aim developed, of elucidating bouton/glial relationships.The second axotomy induced loss and return of subsurface cisterns, dispersal and reassembly of Nissl substance, increase and decrease of microglial numbers, slight further loss and partial return of boutons with clear spherical vesicles and symmetrical synapses, slight increase and decrease of boutons with clear flat vesicles and symmetrical synapses, regrowth of retracted dendrites and restoration of their synapses, and gradual diminution of numbers of electron-dense neurones and dendrites. Astrocytes remained hypertrophied throughout.When compared with events in the hypoglossal nucleus accompanying innervation of denervated sternomastoid muscle by the hypoglossal nerve, the results suggest (1) that regeneration of the hypoglossal nerve to its own tongue muscle instead of to a foreign muscle caused no acceleration of recovery in the hypoglossal nucleus, and (2) that the microglial response is dependent on nerve integrity and not on bouton behaviour.     

Behavior of neurons in the abducens nucleus of the alert cat--III. Axotomized motoneurons

The effects of peripheral and central VIth nerve axotomy on abducens nucleus synaptic potentials of vestibular origin and the ultrastructure of intracellularly labeled abducens motoneurons were examined in the anesthetized cat. Subsequent experiments explored the activity of identified abducens motoneurons during spontaneous and vestibular induced eye movements in alert cats prepared for chronic recordings of eye movements, single units and field potentials. Following axotomy the typical disynaptic inhibition of abducens motoneurons induced by electrical stimulation of the ipsilateral vestibular nerve either disappeared or was reduced for 5-30 days. Disynaptic activation produced by contralateral VIIIth nerve stimulation was apparently not affected. These changes were accompanied at the ultrastructural level by a decrease of axosomatic pleiomorphic synaptic endings. No changes were observed in either the number or distribution of synaptic endings on proximal and distal dendrites. Although not expected by results obtained in acute experiments, axotomized motoneurons showed a decreased excitability in the behavioral paradigm. Amplitude of the abducens antidromic field potential was significantly reduced 4-6 days following axotomy and frequent failures were observed in the antidromic somadendritic invasion of single motoneurons. Somatic invasion was obtained by the simultaneous presentation of appropriate visual and/or vestibular synaptic activity. Chronic recordings of field potentials showed their amplitude to recover in 30-40 days. The spontaneous and vestibular induced activity of identified axotomized motoneurons during this period of time differed in several aspects from controls. Motoneurons could not maintain tonic activity during eye fixations and they showed short, low frequency, bursts of activity that followed, rather than preceded, on-directed saccades. In some cases axotomized motoneurons fired during horizontal off-directed and vertical saccades. Position and velocity gains of axotomized motoneurons were lower than control values. The effects of central axotomy were always larger and of longer duration than those following peripheral axotomy. Structural and functional properties influenced by axotomy seemed to recover in 2-3 months, but with independent time courses. The present results differ in many aspects from those described after axotomy in spinal and hypoglossal motoneurons. In addition, they point out that behavior or axotomized neurons in chronic preparations are not predictable on the basis of those described in acute experiments.     

Effects of axotomy on synaptic transmission and structure in frog sympathetic ganglia

Summary Axotomy was carried out on frog sympathetic neurons of the two last lumbar chain ganglia. At different times thereafter, synaptic transmission was analysed electrophysiologically by intracellular microelectrodes and compared with synaptic density, measured by electron microscopy in the same ganglia. For this purpose, modifications in synaptic transmission were estimated first, by the numbers of B and C sympathetic neurons exhibiting subthreshold excitatory postsynaptic potentials in response to 10 Hz orthodromic stimulation of preganglionic fibres, and second, by the amplitude and number of excitatory postsynaptic potentials occurring over 5–10 s periods of 10 Hz stimulation. By distinguishing two types of morphological relationships between the pre- and postsynaptic elements, two contact indices were defined: a synaptic index (ratio of the number of synapses encountered to the number of perikarya explored) and a simple contact index corresponding to the same type of contacts, but without any membrane differentiation.Both the electrophysiological and morphological results showed that the first effects were detectable 4 days after axotomy, and that the main alterations in synaptic transmission and density occurred at 2 weeks. In addition, while in normal ganglia the excitatory postsynaptic potentials of B and C neurons reached the threshold for action potential generation in response to 10 Hz stimulation, about 29% of the axotomized neurons had subthreshold excitatory postsynaptic potentials 1 week after section. At 2 weeks, this proportion reached 65%, and the synaptic and simple contact indices, at 90% and 60% respectively, were significantly lower than the control ganglion indices.At longer times after axotomy, there was a discrepancy between the morphological and electrophysiological results: at 1 month, the synaptic index seemed to rise as the decline in the efficacy of synaptic transmission became more marked. The amplitude of the subthreshold excitatory postsynaptic potentials recorded in B neurons was 5.5 ± 2.8 mV (mean ± SD,n=18); this value was significantly lower by about 50% than that measured 1 week after axotomy. In addition, the number of excitatory postsynaptic potentials in B neurons reached an average maximum of 83 ± 29 for 100 stimuli applied at 10 Hz. Similar results were obtained for C neurons. Two months after axotomy, the physiological and morphological parameters of synaptic efficacy began to recover and return to normal values, but had not reached them by 4 months.These observations show that some synaptic transmission remains possible, even with a much reduced number of synaptic complexes. It is suggested that after axotomy, simple contacts also might be involved in synaptic transmission.     

The effects of dibutyryl cyclic adenosine monophosphate on the degeneration and regeneration of crush-lesioned rat sciatic nerves

The ability of N⁶,O²-dibutyryl adenosine 3′,5′-monophosphate [(But)₂cAMP to stimulate nerve developmentin vitro prompted us to study the effects of the nucleotide on thein vivo degeneration and regeneration of crushed rat sciatic nerves. The animals received daily intramuscular injections of either (But)₂cAMP (50 mg/kg) or 0.9% saline following surgery and were tested daily for the return of sensorimotor function. An index of sensorimotor function was obtained by placing the foot of the lesioned limb over the aperture of a shutter-controlled high intensity light ?. The time required for foot withdrawal was recorded to the nearest second. (But)₂cAMP and saline-treated rats showed little difference in the rate of return of sensorimotor function for 10 days, but by day 12, the response times for the nucleotide-treated animals diverged from those in the saline-treated group. Nucleotide-treated animals showed complete recovery of the withdrawal reflex by day 16, while saline treated rats did not exhibit full recovery until day 26.To investigate the morphological changes that accompanied this functional recovery, rats were killed 3, 10, 18 and 32 days following crush and their nerves prepared for transmission and scanning electron microscopy. These observations, fibre counts and measurements of fibre size indicated that (But)₂cAMP accelerated the initial processes of Wallerian degeneration and enhanced the rate of increase in myelinated fibre numbers and diameters. The crushed nerves of nucleotide-treated animals generally appeared 7–8 days more advanced in their degenerative and regenerative processes than the saline controls.     

Dopamine regulates synaptic transmission mediated by cholinergic neurons of the rat retina

The purpose of this study was to investigate the effect of dopamine on the function of synapses formed by cholinergic neurons derived from the rat retina. We used an experimental culture system in which rat striated muscle cells served as postsynaptic targets for cholinergic neurons of the retina. This culture system permitted the physiological monitoring of acetylcholine release at synapses formed by retinal neurons. We found that dopamine could facilitate evoked transmission at retina-muscle synapses. This facilitation by dopamine was reversible and could be blocked by haloperidol, a dopamine receptor antagonist. The adenosine 3':5'-phosphate analogue, 8-bromoadenosine 3':5'-phosphate, mimicked the facilitating effect of dopamine. In addition, dopamine elevated markedly the levels of adenosine 3':5'-phosphate in cultures of rat retinal cells. The results suggest that dopamine can regulate transmission through retinal neurons. Our findings support the hypothesis that a dopamine-induced facilitation of stimulus-evoked transmission involves the activation of dopamine receptors and the intracellular accumulation of adenosine 3':5'-phosphate.     

Synaptic interactions of retrogradely labeled hypoglossal motoneurons with substance P-like immunoreactive nerve terminals in the cat: a dual-labeling electron microscopic study

This study has investigated the synaptic interactions between hypoglossal motoneurons and substance P (SP)-immunoreactive terminals. Cholera toxin B conjugated to horseradish peroxidase was injected into the tip of the tongue on the right side of six ketamine-anesthetized cats. Two to five days later, the animals were killed. Cells containing HRP were labeled with a histochemical reaction utilizing tetramethylbenzidine (TMB) as the chromogen. TMB forms crystalline reaction products that are very distinct at the electron microscopic level. The tissues were then processed for immunocytochemisty using an antiserum against SP. The chromogen used in this case, di-aminobenzidine, yields amorphous reaction products. At the light microscopic level, labeled cells were observed primarily ipsilaterally in both intermediate and ventrolateral subdivisions of the hypoglossal nucleus. The majority of these labeled cells were seen at the level of obex. At the electron microscopic level, both asymmetric and symmetric synapses were observed. SP-immunoreactive nerve terminals formed asymmetric synapses with labeled dendrites and symmetric synapses with labeled perikarya. SP-labeled terminals also synapsed on unlabeled dendrites and somata. These are the first ultrastructural studies demonstrating synaptic interactions between hypoglossal motoneurons and SP terminals. These studies demonstrate that hypoglossal motoneurons that innervate intrinsic tongue muscles are modulated by SP and that SP may play a role in the control of fine movements of the tongue.