Functional properties of brainstem motoneurons following their reinnervation of native or foreign muscles.
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Animals↗
Biomedical subjects
J M Delgado-García
Publications and source records attributed to J M Delgado-García.
Motoneuron adaptability to new motor tasks following two types of facial-facial anastomosis in cats.
The ability of the facial motor system to adapt to a new motor function was studied in alert cats after unilateral transection, 180 degrees rotation and suture of the zygomatic nerve, or transection and cross-anastomosis of the proximal stump of the buccal nerve to the distal stump of the zygomatic nerve. These procedures induced reinnervation of the orbicularis oculi (OO) muscle by different OO- or mouth-related facial motoneurons. Eyelid movements and the electromyographic activity of the OO muscle were recorded up to 1 year following the two types of anastomosis. Animals with a zygomatic nerve rotation recovered spontaneous and reflex responses, but with evident deficits in eyelid kinematics, i.e. the proper regional distribution of OO motor units was disorganized by zygomatic nerve rotation and resuture, producing a permanent defect in eyelid motor performance. Following buccal-zygomatic anastomosis, the electrical activity of the OO muscle was recovered after 6-7 weeks, but air puff-, flash- and tone-evoked reflex blinks never reached the control values on the operated side. Electromyographic OO activities and lid movements corresponding to licking and deglutition activities were observed on the operated side in buccal-zygomatic anastomosed animals up to 1 year following surgery. Mouth-related facial motoneurons did not readapt their discharges to the kinetic, timing and oscillatory properties of OO muscle fibres. A significant hyper-reflexia was observed following both types of nerve repair in response to air puffs, but not to light flashes or tones. In conclusion, adult mammal facial premotor circuits maintain their motor programmes when motoneurons are induced to reinnervate a foreign muscle, or even a new set of muscle fibres.
Adaptation, Physiological↗
The role of interpositus nucleus in eyelid conditioned responses.
One of the most widely used experimental models for the study of learning processes in mammals has been the classical conditioning of nictitating membrane/eyelid responses, using both trace and delay paradigms. Mainly on the basis of permanent or transitory lesions of putatively-involved structures, and using other stimulation and recording techniques, it has been proposed that cerebellar cortex and/or nuclei could be the place/s where this elemental form of associative learning is acquired and stored. We have used here an output-to-input approach to review recent evidence regarding the involvement of the cerebellar interpositus nucleus in the acquisition of these conditioned responses (CRs). Eyelid CRs appear to be different in profile, duration, and peak velocity from reflexively-evoked blinks. In addition, CRs are generated in a quantum manner across conditioning sessions, suggesting a gradual neural process for their proper acquisition. Accessory abducens and orbicularis oculi motoneurons have different membrane properties and contribute differently to the generation of CRs, with significant species differences. In particular, facial motoneurons seem to encode eyelid velocity during reflexively-evoked blinks and eyelid position during CRs, two facts suggestive of a differential somatic versus dendritic arrival of specific motor commands for each type of movement. Identified interpositus neurons recorded in alert cats during classical conditioning of eyelid responses show firing properties suggestive of an enhancing role for CR performance. However, as their firing started after CR onset, and because they do not seem to encode eyelid position during the CR, the interpositus nucleus cannot be conclusively considered as the place where this acquired motor response is generated. More information is needed regarding neural signal transformations taking place in each involved neural center, and it its proposed that more attention should be paid to functional states (as opposed to neural sites) able to generate motor learning in mammals. The contribution of feedforward mechanisms normally involved in the processing activities of related centers and circuits, and the possible functional interactions within neural systems subserving the associative strength between the conditioned and unconditioned stimuli, are also considered.
Action Potentials↗
Hypoglossal and reticular interneurons involved in oro-facial coordination in the rat.
Chewing, swallowing, breathing, and vocalization in mammals require precise coordination of tongue movements with concomitant activities of the mimetic muscles. The neuroanatomic basis for this oro-facial coordination is not yet fully understood. After the stereotaxic microinjection of retrograde and anterograde neuronal tracers (biotin-dextran, Fluoro-Ruby, Fluoro-Emerald, and Fluoro-Gold) into the facial and hypoglossal nuclei of the rat, we report here a direct bilateral projection of hypoglossal internuclear interneurons onto facial motoneurons. We also confirm the existence of a small pool of neurons in the dorsal part of the brainstem reticular formation that project ipsilaterally to both facial and hypoglossal nuclei. For precise tracer injections, both motor nuclei were located and identified by the electrical antidromic activation of their constituent motoneurons. Injections of retrograde tracers into the facial nucleus consistently labeled neurons in the hypoglossal nucleus. These neurons prevalently lay in the ipsilateral side, were small in size, and, like classic intrinsic hypoglossal local-circuit interneurons, had several thin dendrites. Reverse experiments - injections of anterograde tracers into the hypoglossal nucleus - labeled fine varicose nerve fiber terminals in the facial nucleus. These fiber terminals were concentrated in the intermediate subdivision of the facial nucleus, with a strong ipsilateral prevalence. Double injections of different tracers into the facial and the hypoglossal nuclei revealed a small, but constant, number of double-labeled neurons located predominantly ipsilateral in the caudal brainstem reticular formation. Hypoglossal internuclear interneurons projecting to the facial nucleus, as well as those neurons of the parvocellular reticular formation that project to both facial and hypoglossal nuclei, could be involved in oro-facial coordination.
Animals↗
Reversible deafferentation of abducens motoneurons and internuclear neurons with tetanus neurotoxin.
Tetanus neurotoxin (TeNT) is a blocker of synaptic vesicle exocytosis in central synapses with preferential affinity for inhibitory neurotransmission. Following its intramuscular injection, TeNT is retrogradely and trans-synaptically transported towards the premotor terminals. Therefore, we have used TeNT as a tool to study the consequences of functional deafferentation on motoneurons following its peripheral administration. For this, we injected the toxin into the lateral rectus muscle at doses of 5 or 0.5 ng/kg and recorded the discharge activity of abducens motoneurons and internuclear neurons in the alert cat. Our results showed that: (i) TeNT blocked selectively the afferent inhibitory signals on abducens neurons only when used at a low dose, whereas both excitatory and inhibitory synaptic drive was lost after the high dose treatment; (ii) all effects were reversible within one month; and (iii) strikingly, the internuclear neurons of the abducens nucleus showed similar discharge alterations to the motoneurons, suggesting a TeNT action on shared common afferences.
Abducens Nerve↗
Harmaline induces different motor effects on facial vs. skeletal-motor systems in alert cats.
Harmaline's effects on reflex and classically conditioned eyelid responses and on tremor picked up by a coil attached to the back were measured in alert cats. Harmaline at a dose of 10 mg/kg produced skeletal muscle tremogenic effects that lasted 4h. Back movements presented a tremor-like displacement with a frequency peak at 10 Hz, but lid responses oscillated as in controls, at 20 Hz during both reflex and conditioned eyelid movements, with no increase in oscillation amplitude or frequency. The learning curves of harmaline-injected animals remained as in controls, but eyelid conditioned responses showed longer latencies, and smaller amplitude and peak velocity. Reflex and already-learned eyelid responses were not modified by harmaline. These results imply that neuronal control systems for skeletal-motor and facial responses are differentially affected by harmaline.
Journal Article↗
Hippocampal pyramidal cell activity encodes conditioned stimulus predictive value during classical conditioning in alert cats.
We have recorded the firing activities of hippocampal pyramidal cells throughout the classical conditioning of eyelid responses in alert cats. Pyramidal cells (n = 220) were identified by their antidromic activation from the ipsilateral fornix and according to their spike properties. Upper eyelid movements were recorded with the search coil in a magnetic field technique. Latencies and firing profiles of recorded pyramidal cells following the paired presentation of conditioned (CS) and unconditioned (US) stimuli were similar, regardless of the different sensory modalities used as CS (tones, air puffs), the different conditioning paradigms (trace, delay), or the different latency and topography of the evoked eyelid conditioned responses. However, for the three paradigms used here, evoked neuronal firing to CS presentation increased across conditioning, but remained unchanged for US presentation. Contrarily, pyramidal cell firing was not modified when the same stimuli used here as CS and US were presented unpaired, during pseudoconditioning sessions. Pyramidal cell firing did not seem to encode eyelid position, velocity, or acceleration for either reflex or conditioned eyelid responses. Evoked pyramidal cell responses were always in coincidence with a beta oscillatory activity in hippocampal extracellular field potentials. In this regard, the beta rhythm represents a facilitation, or permissive time window, for timed pyramidal cell firing. It is concluded that pyramidal cells encode CS-US associative strength or CS predictive value.
Acoustic Stimulation↗
Response of abducens internuclear neurons to axotomy in the adult cat.
The highly specific projection of abducens internuclear neurons on the medial rectus motoneurons of the oculomotor nucleus constitutes an optimal model for investigating the effects of axotomy in the central nervous system. We have analyzed the morphological changes induced by this lesion on both the cell bodies and the transected axons of abducens internuclear neurons in the adult cat. Axotomy was performed by the transection of the medial longitudinal fascicle. Cell counts of Nissl-stained material and calretinin-immunostained abducens internuclear neurons revealed no cell death by 3 months postaxotomy. Ultrastructural examination of these cells at 6, 14, 24, and 90 days postaxotomy showed normal cytological features. However, the surface membrane of axotomized neurons appeared contacted by very few synaptic boutons compared to controls. This change was quantified by measuring the percentage of synaptic coverage of the cell bodies and the linear density of boutons. Both parameters decreased significantly after axotomy, with the lowest values at 90 days postlesion ( approximately 70% reduction). We also explored axonal regrowth and the possibility of reinnervation of a new target by means of anterograde labeling with biocytin. At all time intervals analyzed, labeled axons were observed to be interrupted at the caudal limit of the lesion; in no case did they cross the scar tissue to reach the distal part of the tract. Nonetheless, a conspicuous axonal sprouting was present at the caudal aspect of the lesion site. Structures suggestive of axonal growth were found, such as large terminal clubs, from which short filopodium-like branches frequently emerged. Similar findings were obtained after parvalbumin and calretinin immunostaining. At the electron microscopy level, biocytin-labeled boutons originating from the sprouts appeared surrounded by either extracellular space, which was extremely dilated at the lesion site, or by glial processes. The great majority of labeled boutons examined were, thus, devoid of neuronal contact, indicating absence of reinnervation of a new target. Altogether, these data indicate that abducens internuclear neurons survive axotomy in the adult cat and show some form of axonal regrowth, even in the absence of target connection.
Abducens Nerve↗
Discharge characteristics of axotomized abducens internuclear neurons in the adult cat.
The aim of the present work was to characterize the axotomy-induced changes in the discharge properties of central nervous system neurons recorded in the alert behaving animal. The abducens internuclear neurons of the adult cat were the chosen model. The axons of these neurons course through the contralateral medial longitudinal fascicle and contact the medial rectus motoneurons of the oculomotor nucleus. Axotomy was carried out by the unilateral transection of this fascicle (right side) and produced immediate oculomotor deficits, mainly the incapacity of the right eye to adduct across the midline. Extracellular single-unit recording of abducens neurons was carried out simultaneously with eye movements. The main alteration observed in the firing of these axotomized neurons was the overall decrease in firing rate. During eye fixations, the tonic signal was reduced, and, on occasion, a progressive decay in firing rate was observed. On-directed saccades were not accompanied by the high-frequency spike burst typical of controls; instead, there was a moderate increase in firing. Similarly, during the vestibular nystagmus, neurons hardly modulated during both the slow and the fast phases. Linear regression analysis between firing rate and eye movement parameters showed a significant reduction in eye position and velocity sensitivities with respect to controls, during both spontaneous and vestibularly induced eye movements. These firing alterations were observed during the 3 month period of study after lesion, with no sign of recovery. Conversely, abducens motoneurons showed no significant alteration in their firing pattern. Therefore, axotomy produced long-lasting changes in the discharge characteristics of abducens internuclear neurons that presumably reflected the loss of afferent oculomotor signals. These alterations might be due to the absence of trophic influences derived from the target.
Abducens Nerve↗
Scopolamine impairs information processing in the hippocampus and performance of a learned eyeblink response in alert cats.
The object of this work was to determine whether the changes in field activity and neuronal excitability recorded in the hippocampus during eyeblink classical conditioning are induced by the cholinergic input, and their relationships with the conditioned response performance. The pyramidal layer field activity, its response to fornix stimulation and eyelid responses were recorded during paired tone-air puff presentations, under scopolamine (25, 50 and 100 microg/kg) or saline administration, following well-established eyeblink conditioning in a trace paradigm in cats. Scopolamine impaired behavioral performance, and, in the hippocampus, disrupted conditioned stimulus-evoked field potential, high frequency shift in field activity, and paired presentation-induced hyperexcitability. These findings indicate that the cholinergic input participates in hippocampal information processing in a way that allows precise conditioned response performance and memory trace formation.
Animals↗
Limits to the capacity of transplants of olfactory glia to promote axonal regrowth in the CNS.
Olfactory bulb ensheathing cell (OBEC) transplants promoted axonal regeneration in the spinal cord dorsal root entry zone and in the corticospinal tract. However, OBECs failed to promote abducens internuclear neuron axon regeneration when transplanted at the site of nerve fibre transection. In experiments performed in both cats and rats, OBECs survived for up to 2 months, lining themselves up along the portion of the regrowing axons proximal to the interneuron cell body. However, OBECs migrated preferentially towards abducens somata, in the direction opposite to the oculomotor nucleus target. OBECs seem to promote nerve fibre regeneration only where preferred direction of glial migration coincides with the direction of axonal growth towards its target.
Abducens Nerve↗
Involvement of cerebral cortical structures in the classical conditioning of eyelid responses in rabbits.
The classical conditioning of the eyelid motor system in alert behaving rabbits has been used to study the expression of Fos in the hippocampus, and in the occipital, parietal, piriform and temporal cortices. Animals were classically conditioned with both delay and trace conditioning paradigms. As conditioned stimulus, both short and long (20 and 100 ms) tones (600 Hz, 90 dB) or short, weak (20 ms, 1kg/cm(2)) air puffs were used. The unconditioned stimulus was always a long, strong (100 ms, 3 kg/cm(2)) air puff that started 250-270 ms after the onset of the conditioned stimulus. The expression of Fos was significantly increased after both delayed and trace conditioning in the hippocampus, and in the parietal and piriform cortices contralateral to the unconditioned stimulus presentation side, compared with equivalent ipsilateral structures in conditioned animals, or with Fos production in the same contralateral structures in pseudo-conditioned and control animals. Fos expression in some cortical sites was specific to tone versus air puff stimuli when used as conditioned stimulus. Thus, Fos expression was significantly increased in the contralateral temporal lobe when tones were used as conditioned stimulus, for both delayed and trace conditioning paradigms, but not when animals were conditioned to short, weak air puffs. The present results indicate a specific Fos activation in several cerebral cortical structures during associative eyelid conditioning.
Animals↗
Why move the eyes if we can move the head?
To see while moving is a very basic and integrative sensorimotor function in vertebrates. To maintain visual acuity, the oculomotor system provides efficient compensatory eye movements for head and visual field displacements. Other types of eye movement allow the selection of new visual targets and binocular vision and stereopsis. Motor and premotor neuronal circuits involved in the genesis and control of eye movements are briefly described. The peculiar properties and robust biomechanics of the oculomotor system have allowed it to survive almost unchanged through vertebrate evolution.
Animals↗
Kinetic and frequency-domain properties of reflex and conditioned eyelid responses in the rabbit.
Eyelid position and the electromyographic activity of the orbicularis oculi muscle were recorded unilaterally in rabbits during reflex and conditioned blinks. Air-puff-evoked blinks consisted of a fast downward phase followed sometimes by successive downward sags. The reopening phase had a much longer duration and slower peak velocity. Onset latency, maximum amplitude, peak velocity, and rise time of reflex blinks depended on the intensity and duration of the air puff-evoking stimulus. A flashlight focused on the eye also evoked reflex blinks, but not flashes of light, or tones. Both delayed and trace classical conditioning paradigms were used. For delayed conditioning, animals were presented with a 350-ms, 90-dB, 600-Hz tone, as conditioned stimulus (CS). For trace conditioning, animals were presented with a 10-ms, 1-k/cm(2) air puff, as CS. The unconditioned stimulus (US) consisted of a 100-ms, 3-k/cm(2) air puff. The stimulus interval between CS and US onsets was 250 ms. Conditioned responses (CRs) to tones were composed of downward sags that increased in number through the successive conditioning sessions. The onset latency of the CR decreased across conditioning at the same time as its maximum amplitude and its peak velocity increased, but the time-to-peak of the CR remained unaltered. The topography of CRs evoked by short, weak air puffs as the CS showed three different components: the alpha response to the CS, the CR, and the reflex response to the US. Through conditioning, CRs showed a decrease in onset latency, and an increase in maximum amplitude and peak velocity. The time-to-peak of the CR remained unchanged. A power spectrum analysis of reflex and conditioned blink acceleration profiles showed a significant approximately 8-Hz oscillation within a broadband of frequencies between 4 and 15 Hz. Nose and mandible movements presented power spectrum profiles different from those characterizing reflex and conditioned blinks. It is concluded that eyelid reflex responses in the rabbit present significant differences from CRs in their profiles and metric properties, suggesting different neural origins, but that a common approximately 8-Hz neural oscillator underlies lid motor performance. According to available data, the frequency of this putative oscillator seems to be related to the species size.
Air Movements↗
Cerebellar posterior interpositus nucleus as an enhancer of classically conditioned eyelid responses in alert cats.
Cerebellar posterior interpositus neurons were recorded in cats during delayed and trace conditioning of eyeblinks. Type A neurons increased their firing in the time interval between conditioned and unconditioned stimulus presentations for both paradigms, while type B neurons decreased it. The discharge of different type A neurons recorded across successive conditioning sessions increased, with slopes of 0.061-0.078 spikes/s/trial. Both types of neurons modified their firing several trials in advance of the appearance of eyelid conditioned responses, but for each conditioned stimulus presentation their response started after conditioned response onset. Interpositus microstimulation evoked eyelid responses similar in amplitude and profiles to conditioned responses, and microinjection of muscimol decreased conditioned response amplitude. It is proposed that the interpositus nucleus is an enhancer, but not the initiator, of eyelid conditioned responses.
Action Potentials↗
Different discharge properties of rat facial nucleus motoneurons.
In this paper, we describe two types of putative facial motoneuron based on their electrophysiological properties and on their firing frequency adaptation as recorded in rat brainstem slices. Type I motoneurons (n = 33, 61%) were characterized by a sustained spike firing during depolarizing current injections and a marked depolarizing sag (inward rectification) during hyperpolarizing pulses. The time-course and voltage-dependence of the inward rectification together with the finding that it was blocked by Cs+ are consistent with the involvement of a Na+ -and K+ -mediated Q current. Type II motoneurons (n = 21, 39%) were identified by a fast spike firing adaptation. Type II cells showed a less pronounced inward rectification with hyperpolarizing current pulses and a higher discharge rate than type I cells during depolarizing current pulses. These distinct discharge properties imply the activation of a Ca2+ -dependent K+ current, because when carbachol was added to the bath, or the slice was exposed to a Ca2+ -free solution, a decrease was noticed in the firing frequency adaptation. The two types of motoneuron were further differentiated by the initial delay of the first spike, observed only in type I cells, which was blocked by bath application of 4-aminopyridine, indicating the presence of a K+ -mediated A current. The addition of 4-aminopyridine to the bath also increased the firing rate due to a decrease of the post-spike afterhyperpolarization. However, the two types of motoneuron were not morphologically differentiated. Facial motoneurons exhibited rhythmic membrane potential oscillations (8-20 Hz) at depolarized membrane potentials or during the silence following spike frequency adaptation. It is suggested that the intrinsic properties of these two types of facial motoneuron may be relevant in the government of distinct facial muscle activities. The fact that their discharge rate and the level of spike frequency adaptation were modified by altering some K+ currents suggests a potential plasticity in the modulation of motoneuron firing activities depending upon functional motor needs.
4-Aminopyridine↗
Discharge profiles of abducens, accessory abducens, and orbicularis oculi motoneurons during reflex and conditioned blinks in alert cats.
The discharge profiles of identified abducens, accessory abducens, and orbicularis oculi motoneurons have been recorded extra- and intracellularly in alert behaving cats during spontaneous, reflexively evoked, and classically conditioned eyelid responses. The movement of the upper lid and the electromyographic activity of the orbicularis oculi muscle also were recorded. Animals were conditioned by short, weak air puffs or 350-ms tones as conditioned stimuli (CS) and long, strong air puffs as unconditioned stimulus (US) using both trace and delayed conditioning paradigms. Motoneurons were identified by antidromic activation from their respective cranial nerves. Orbicularis oculi and accessory abducens motoneurons fired an early, double burst of action potentials (at 4-6 and 10-16 ms) in response to air puffs or to the electrical stimulation of the supraorbital nerve. Orbicularis oculi, but not accessory abducens, motoneurons fired in response to flash and tone presentations. Only 10-15% of recorded abducens motoneurons fired a late, weak burst after air puff, supraorbital nerve, and flash stimulations. Spontaneous fasciculations of the orbicularis oculi muscle and the activity of single orbicularis oculi motoneurons that generated them also were recorded. The activation of orbicularis oculi motoneurons during the acquisition of classically conditioned eyelid responses happened in a gradual, sequential manner. Initially, some putative excitatory synaptic potentials were observed in the time window corresponding to the CS-US interval; by the second to the fourth conditioning session, some isolated action potentials appeared that increased in number until some small movements were noticed in eyelid position traces. No accessory abducens motoneuron fired and no abducens motoneuron modified their discharge rate for conditioned eyelid responses. The firing of orbicularis oculi motoneurons was related linearly to lid velocity during reflex blinks but to lid position during conditioned responses, a fact indicating the different neural origin and coding of both types of motor commands. The power spectra of both reflex and conditioned lid responses showed a dominant peak at approximately 20 Hz. The wavy appearance of both reflex and conditioned eyelid responses was clearly the result of the high phasic activity of orbicularis oculi motor units. Orbicularis oculi motoneuron membrane potentials oscillated at approximately 20 Hz after supraorbital nerve stimulation and during other reflex and conditioned eyelid movements. The oscillation seemed to be the result of both intrinsic (spike afterhyperpolarization lasting approximately 50 ms, and late depolarizations) and extrinsic properties of the motoneuronal pool and of the circuits involved in eye blinks.
Abducens Nerve↗
Effects of botulinum neurotoxin type A on the expression of gephyrin in cat abducens motoneurons.
In this study, we investigated the effects of long-term synaptic blockade on postsynaptic receptor clustering at central inhibitory glycinergic synapses. High doses of botulinum neurotoxin type A injected in the lateral rectus muscle completely abolishes inhibitory postsynaptic potentials onto abducens motoneurons within 2 days postinjection, and transmission remains blocked for at least 2 months. Using this model, we analyzed the expression of gephyrin, a glycine receptor clustering protein, on the membrane of motoneuron somata after botulinum neurotoxin type A injection in their target muscle. Immunofluorescence or electron microscopy immunohistochemistry revealed gephyrin-immunoreactive clusters (most < 0.5 microm in diameter) densely covering the surface of control abducens motoneurons. Ultrastructurally, presynaptic terminals containing flattened synaptic vesicles (F terminals) were found associated with multiple gephyrin-immunoreactive postsynaptic densities (average 1.24 gephyrin clusters/F+ profile). No significant changes in gephyrin-immunoreactive clusters were observed at 5 days postinjection, but we found significant reductions (25-40%) in the density of gephyrin clusters 19 and 35 days postinjection. Hence, the physiological alterations reported in this model precede structural changes on postsynaptic receptor cluster density. The decrease in gephyrin-immunoreactive clusters was paralleled by reductions in synaptic covering (F+ terminals per 100 microm of membrane). Presumed inactive F+ terminals that remained attached to the motoneuron surface displayed normal gephyrin-immunoreactive clusters; however, the pre- and postsynaptic membranes in between synaptic active zones frequently appeared separated by enlarged extracellular spaces. We concluded that postsynaptic receptor cluster dissolution seemed more directly related to terminal retraction than to inactivity alone.
Abducens Nerve↗