Individual Motoneurons Research Articles

Iontophoretic analysis of the pharmacologic mechanisms responsible for initiation and modulation of trigeminal motoneuronal discharge evoked by intra-oral afferent stimulation

This study investigated the effects of iontophoretic application of excitatory amino acid (EAA) and norepinephrine (NE) agonists and antagonists on synaptic transmission to individual jaw-opener motoneurons (digastric) during activation of the jaw-opening reflex (JOR) evoked by stimulation of either fibers within the oral mucosa (OM), or tooth-pulp (TP). During both OM and TP stimulation, kynurenic acid (KYN), a wide-spectrum EAA antagonist, suppressed jaw-opener motoneuron discharge. Application of APV, an NMDA receptor antagonist, also suppressed motoneuron discharge evoked by TP stimulation, but produced minimal effects on motoneuron discharge evoked by OM stimulation. These data suggest a role of EAA in mediating synaptic transmission from last-order interneurons to jaw-opener motoneurons during the jaw-opening reflex evoked by intra-oral stimulation. Iontophoretic application of NE produced dual effects (facilitation or suppression) on motoneuronal discharge evoked by OM or TP stimulation. The effects were not related to the mode of motoneuronal activation. Iontophoretic application of the alpha 1 agonist, phenylephrine, facilitated motoneuronal discharge. In contrast, application of the alpha 2 agonist, clonidine, suppressed motoneuronal discharge during intra-oral stimulation. These effects were antagonized by prior iontophoretic application of the alpha 1 antagonist, prazosin, or the alpha 2 antagonist, yohimbine, respectively. In those cells in which the predominant effect of NE application on synaptic transmission was either facilitation or suppression of motoneuronal discharge, prior iontophoretic application of prazosin or yohimbine, respectively, antagonized the effects of NE application. These data suggest that NE can modulate synaptic transmission to jaw-opener motoneurons evoked by intra-oral stimulation via activation of alpha 1 or alpha 2 adrenoreceptors on trigeminal motoneurons.

Proprioceptive reflex interactions with central motor rhythms in the isolated thoracic ganglion of the shore crab

Experiments were carried out on an isolated central nervous system preparation of the shore crab,Carcinus maenas, comprising the fused thoracic ganglion complex with two proprioceptors of one back leg still attached. These, the thoracic-coxal muscle receptor organ and the coxo-basal chordotonal organ, monitor movement and position of the first and second joints, respectively. Motor activity was recorded extracellularly from the central cut ends of the nerves innervating the promotor and remotor muscles of the thoracic-coxal joint, and the levator and depressor muscles of the coxal-basal joint of the same leg. Simultaneous intracellular recordings were made from central processes of individual motoneurones of each muscle.

Location and connectivity of abdominal motoneurons in the embryo and larva of Drosophila melanogaster

The soma location and peripheral connectivity of motoneurons in abdominal segments of the embryo and larva of the fruitfly, Drosophila melanogaster are described as an initial step in determining the mechanisms by which motoneurons make connections with their target muscles in a genetically accessible organism. Embryonic motoneuron somata were retrogradely labelled by application of the fluorescent dye, DiI, to the whole peripheral nerve or to its separate anterior or posterior fascicles in segments A5-A7 of late stage 15/early stage 16 embryos. This technique reveals a stereotyped, segmentally repeated population of 34 motoneurons per hemisegment, several of which can be individually identified from their soma position. The same set of motoneurons was revealed in third instar larvae of D. melanogaster by cobalt backfilling of abdominal peripheral nerves, although the positions of some of these neurons change during larval development. The peripheral connectivity and axon morphology of several of the abdominal motoneurons was determined by intracellular injection with Lucifer Yellow in stage 16 embryos. For the motoneurons with axons in the anterior fascicle there is no clear relationship between somata groupings and the muscle targets innervated: contrary to earlier claims, these motoneurons arborize over both ventral and dorsal muscles. Individual motoneurons possess a stereotyped pattern of terminal arborization.

Expression of diverse neuropeptide cotransmitters by identified motor neurons in Aplysia

Neuropeptide synthesis was determined for individual identified ventral-cluster neurons in the buccal ganglia of Aplysia. Each of these cells was shown to be a motor neuron that innervates buccal muscles that generate biting and swallowing movements during feeding. Individual neurons were identified by a battery of physiological criteria and stained with intracellular injection of a vital dye, and the ganglia were incubated in 35S-methionine. Peptide synthesis was determined by measuring labeled peptides in extracts from individually dissected neuronal cell bodies analyzed by HPLC. Previously characterized peptides found to be synthesized included buccalin, FMRFamide, myomodulin, and the 2 small cardioactive peptides (SCPs). Each of these neuropeptides has been shown to modulate buccal muscle responses to motor neuron stimulation. Two other peptides were found to be synthesized in individual motor neurons. One peptide, which was consistently observed in neurons that also synthesized myomodulin, is likely to be the recently sequenced myomodulin B. The other peptide was observed in a subset of the neurons that synthesize FMRFamide. While identified motor neurons consistently synthesized the same peptide(s), neurons that innervate the same muscle often express different peptides. Neurons that synthesized the SCPs also contained SCP-like activity, as determined by snail heart bioassay. Our results indicate that every identified motor neuron synthesizes a subset of these methionine-containing peptides, and that several neurons consistently synthesize peptides that are likely to be processed from multiple precursors.

Peptidergic motoneurons in the buccal ganglia of Aplysia californica Immunocytochemical, morphological, and physiological characterizations

We used physiological recordings, intracellular dye injections and immunocytochemistry to further identify and characterize neurons in the buccal ganglia of Aplysia californica expressing Small Cardioactive Peptide-like immunoreactivity (SCP-LI). Neurons were identified based upon soma size and position, input from premotor cells B4 and B5, axonal projections, muscle innervation patterns, and neuromuscular synaptic properties. SCP-LI was observed in several large ventral neurons including B6, B7, B9, B10, and B11, groups of s1 and s2 cluster cells, at least one cell located at a branch point of buccal nerve n2, and the previously characterized neurons B1, B2 and B15. B6, B7, B9, B10 and B11 are motoneurons to intrinsic muscles of the buccal mass, each displaying a unique innervation pattern and neuromuscular plasticity. Combined, these motoneurons innervate all major intrinsic buccal muscles (I1/I3, I2, I4, I5, I6). Correspondingly, SCP-LI processes were observed on all of these muscles. Innervation of multiple nonhomologous buccal muscles by individual motoneurons having extremely plastic neuromuscular synapses, represents a unique form of neuromuscular organization which is prevalent in this system. Our results show numerous SCPergic buccal motoneurons with widespread ganglionic processes and buccal muscle innervation, and support extensive use of SCPs in the control of feeding musculature.

Axotomy-like changes in cat motoneuron electrical properties elicited by botulinum toxin depend on the complete elimination of neuromuscular transmission

The electrical properties of cat medial gastrocnemius (MG) spinal motoneurons were studied 14-21 d following injection of type A botulinum toxin (BTX) into the MG muscle. Treated MG muscles were atrophic, displayed pronounced fibrillation activity, and were markedly but not completely paralyzed. MG motoneuron electrical properties from animals with the highest MG muscle-twitch forces (greater than 20 gm) appeared normal, while motoneuron properties from animals with the lowest MG muscle-twitch forces (less than 10 gm) exhibited axotomy-like changes, though these changes were less pronounced than after axotomy itself. No changes in the axonal conduction velocity were observed, however. Motoneuron connectivity with MG muscle fibers was determined following intracellular stimulation of MG motoneurons by averaging EMG signals from 3 or 4 pairs of recording electrodes inserted into the BTX-treated MG muscles. Normal electrical properties were observed among motoneurons in which detectable EMG activity linked to the intracellular stimulation pulse was observed. The level of this connectivity, however, indicated that a relatively small number of muscle fibers were activated by individual motoneuron action potentials. Axotomy-like changes of electrical properties were observed in MG motoneurons that could not be associated with detectable EMG activity in the BTX-treated MG muscle following repeated trials of intracellular stimulation. These results indicate that the existence of effective neuromuscular transmission at a small number of motor terminals is sufficient to prevent the appearance of axotomy-like changes in motoneuron electrical properties, and that the absence of such transmission at all motor terminals is associated with the appearance of axotomy-like changes. The results suggest that the effects of axotomy itself on motoneuron properties may be based upon the loss or elimination of a potent interaction between muscle and motoneurons normally mediated by neuromuscular transmission.

Distribution of effective synaptic currents underlying recurrent inhibition in cat triceps surae motoneurons

1. Steady-state recurrent (Renshaw) inhibitory postsynaptic potentials (RIPSPs) were evoked in cat triceps surae motoneurons by stimulating the heteronymous muscle nerve at 100 Hz after dorsal root section. The effective synaptic currents (i.e., the net synaptic current measured at the soma, IN) underlying these inhibitory potentials were measured with a modified voltage-clamp technique. 2. The average value of the effective synaptic currents measured in medial gastrocnemius (MG) motoneurons was 0.4 nA. There was no significant correlation between the IN measured in individual cells and motoneuron input resistance (RN), rheobase (IR), duration of the spike afterhyperpolarization (AHPt1/2), or putative motor-unit type, although the steady-state inhibitory post-synaptic potential (IPSP) amplitudes were correlated with all of these parameters. 3. Steady-state recurrent inhibition was accompanied by a small (3.5%, on average) decrease in the resting input resistance of the motoneurons. The small magnitude of this measured change supports the hypothesis of Burke et al. that the site of synaptic contact between Renshaw cells and motoneurons is somewhat distal to the cell soma. 4. The absence of a differential distribution of the effective synaptic currents generated by Renshaw cells within the MG pool does not support the idea that recurrent inhibition mediates a selective reduction of the firing of small, low-threshold motoneurons by large, high-threshold motoneurons. The small amplitude of the effective synaptic currents we measured suggests that the contribution of recurrent inhibition to the direct modulation of motoneuron firing rate is subtle and that it is perhaps principally involved in the fine control and smooth production of muscle force.

Relation between structural and release parameters at the young rat sensorimotor connection

The present work was carried out on isolated spinal cords of young rats. The aim of this study was the combined morphological and electrophysiological investigation of sensorimotor connections labelled with horseradish peroxidase and the evaluation of the relationship between their structural and functional properties. Sensorimotor contacts were widely distributed along the postsynaptic cell: from the soma and juxtasomatic dendrites to distal dendrites. The number of contacting boutons in the connection of a single afferent fibre and an individual motoneuron was about 10. The amplitude fluctuation patterns of the unitary and the minimal excitatory postsynaptic potentials of the motoneurons fitted with predictions based on a binomial model. A close correspondence was found between the estimated number of binomial release sites, n, and the number of contacting boutons. The calculated size of the quantal potential was about 100 μV. The difference in the organization of sensorimotor connections of the young rat and the frog is discussed.

Sensory neurons and motoneurons of the jaw-closing reflex pathway in rats: a combined morphological and physiological study using the intracellular horseradish peroxidase technique

Motoneurons and muscle spindle afferents of the rat masseter muscle were physiologically and morphologically characterized. Their soma-dendritic morphology and axonal course were investigated using the intracellular horseradish peroxidase method. Following electrical stimulation of the masseter nerve, individual motoneurons were identified by antidromic all-or-none action potentials and individual sensory neurons by orthodromic action potentials. Using threshold separation an excitatory input from muscle spindles to a masseter motoneuron was demonstrated. The short latency difference of 0.34 ms between the mean orthodromic response in the sensory neurons and the beginning of the synaptic potential in the masseter motoneuron suggests a monosynaptic connection between the spindle afferents and the motoneurons. Following intrasomatic horseradish peroxidase injection large multipolar cell bodies of masseter motoneurons were found within the motor nucleus. Their positions corresponded to the topographic organization of the motor trigeminal nucleus as described in retrograde tracing studies. Dendrites of masseter motoneurons were complex and could be found far beyond the nuclear borders. Distal dendrites extended to the mesencephalic trigeminal nucleus, the supratrigeminal nucleus, the lateral lemniscus and the reticular formation. Within the reticular formation dendrites were seen in the intertrigeminal nucleus and the peritrigeminal zone. Unipolar cell bodies of muscle spindle afferents were found in the mesencephalic trigeminal nucleus after intra-axonal injection of horseradish peroxidase. For all reconstructed sensory neurons a similar axonal course was found. Axonal terminals were found ipsilateral in the motor trigeminal nucleus, indicating a direct connection between sensory neurons and motoneurons. Further collaterals were found ipsilateral in the supratrigeminal nucleus and caudal to the motor trigeminal nucleus in the parvocellular reticular nucleus alpha. Since the latter termination areas are important for bilateral control of jaw-movements, the muscle spindle afferents are likely to participate not only in a monosynaptic motor reflex, but also in more complex neuronal circuits involved in jaw-movements.

Mesothoracic interneurons involved in flight steering in the locust

1. 1. Twenty-eight interneurons with somata in the mesothoracic ganglion of the locust Locusta appear to be involved in steering in flight. All have their arborizations in the dorsal (flight) neuropil. All make directionally selective responses to visual, ocellar or wind stimuli corresponding to simulated deviations from course in flight. All are directly and/or indirectly postsynaptic to one or more sensory descending neurons (DNs) of the brain, which have been shown to produce steering behaviour when electrically stimulated. Convergence of DNs leads to complex responses by the interneurons. Some receive a variety of additional sensory information derived from thoracic receptors, especially wing proprioceptors and the ear. 2. 2. The membrane potentials of all these interneurons are modulated at flight frequency during fictive flight in deafferented preparations. Nineteen are depolarised in depressor phase (and/ or hyperpolarised in elevator phase); nine are depolarised in elevator phase (and/or hyperpolarised in depressor phase). The modulation derives in at least one case (neuron 016), and presumably in all, from synaptic drive from oscillator or oscillator-follower interneurons. None of the described cells, with the possible exception of IN 313, is thought to be part of the oscillator itself. 3. 3. The 28 ‘steering interneurons’ are characterised and named. Five (016, 035, 036, 302, 313) have been previously described in other contexts. Of these, the first 3 have been renamed; they were previously 116, 135 and 136 of Rowell and Pearson (1983). Four other previously named units are synonomized: 318 of Rowell and Pearson (1983) becomes 302 of Robertson and Pearson (1983), and 120 and 119 of Rowell and Pearson (1983), and 1AA of Elson (1987), all become 016. Two new modifications of the numbering system for locust interneurons are introduced. 4. 4. Five steering neurons are known to make monosynaptic, excitatory or inhibitory connections with flight motor neurons. Individual steering interneurons contribute between 25% and 10% of the total oscillatory drive to individual FMNs. 5. 5. The population of steering interneurons is the site of convergence of oscillator drive and sensory input prior to reaching the motor neuron: this allows sensory modulation of the strength and timing of drive to the individual motor neuron in the appropriate phase of the wing beat cycle, which is required for corrective steering. They are also a point at which the motor drive to the motor neuron is modified by proprioceptive reafference.

Activity patterns of motoneurons in the spinal dogfish in relation to changing Active locomotion

Rhythmic motoneuronal activity was recorded from segmental motor nerves of moving (spinal swimming) and paralysed (fictive swimming) spinal dogfish ( Scyliorhinus canicula ), and, in the paralysed preparation, microelectrode recordings were made from spinal cord motoneurons. The motoneurons could be divided into two groups, according to their activity patterns. Group I ( n = 31) were inactive during Active swimming and did not respond to gentle tactile stimulation; when recorded from intracellularly they showed stable to weakly oscillating (< 1 mV) membrane potentials. Group II ( n = 15) fired bursts of action potentials in phase with the motor nerve activity, which were superimposed upon larger (up to 17 mV) depolarizations, and responded to gentle tactile stimulation. Two of these cells discharged also in the interburst interval of the nerve activity. Decreases in cycle period of the Active swimming (i.e. increases in locomotor frequency) were instantaneously accompanied by increases in the amplitude of the rectified and integrated motor nerve signal, which represents peak activity of group II motoneurons, and decreases in the duration of the motor burst. Similar instantaneous changes were seen in the firing frequency and burst duration of individual group II motoneurons. The conformity between unit and population behaviour with changing speed of Active swimming, and the close correspondence observed between the form of the excitatory postsynaptic potentials recorded from individual motoneurons and the form of the integrated neurogram, suggest that the group II motoneurons receive a common excitatory drive. Re- and decruitment of motoneurons were virtually absent during these changes of speed. During unstimulated spinal swimming, regular left—right alternating EMG activity is recorded from the red but not from the white part of the myotome. The ratio of group I to group II motoneurons (31:15) recorded in this study agrees with the previously reported proportion of axons in the spinal motor nerve that project to the white and red muscle fibres, respectively. We suggest, therefore, that group II motoneurons innervate the red and superficial muscle fibres and group I the white fibres. The different activity patterns of the two motoneuronal groups in the spinal fish probably reflect the different ways the red and white muscle systems are used during locomotion

Acoustic signaling in teleost fishes: Model systems for vertebrate vocalization

Teleost fishes can vocalize by contracting striated muscles attached to the lateral walls of their swimbladder. The rhythmic, oscillatory‐like, firing properties of a brain‐stem sonic motor circuit determine the fundamental frequency of the acoustic signals. In the midshipman Porichthys notatus only large, nest‐building, egg‐guarding males generate long duration (up to 1 h) “hums” that attract females to the nests. Females, and smaller, “sneak‐spawning” males, do not hum. Behavorial sex differences in sound production are correlated with: (a) the soma‐dendritic dimensions and discharge frequency of individual sonic motoneurons and their presynaptic pacemaker neurons, (b) the functional architecture of sonic muscle fibers and myofibrils, and (c) the density of neuromodulator inputs to the sonic motor nucleus. The sonic motor circuit can serve as a “simple” model system for a detailed analysis of the synaptic and electro‐responsive properties of single neurons controlling the generation of sex‐ and species‐typical acoustic communication signals. The collaboration of Harriet Baker, Robert Baker, Richard Brantley, and Margaret Marchaterre is acknowledged. [Work supported by NSF, NIH, and Hatch Grants.]

Development of compartmentalized innervation of the rat gluteus maximus muscle

The innervation territories of the nerves to the gluteus maximus muscle were investigated in neonatal rats by using evoked electromyographic mapping techniques. Similar methods were employed to determine the terminal fields of individual motoneurons. Both at birth and after the period of neuromuscular synapse elimination, rat gluteus maximus is partitioned by its two muscle nerves. Each of these partitions is further divided into neuromuscular compartments by the primary branches of the muscle nerves. The terminal fields of individual motoneurons are about as well localized in early neonates as in 26 day-old animals. Intracellular records from gluteal muscle cells reveal that some myotubes in a narrow region near the center of the muscle receive inputs from both of the muscle nerves during the period of polyneuronal innervation. Such cross-compartmental innervation could be demonstrated only until the eighth postnatal day, even though polyneuronally innervated muscle cells were found as late as postnatal day 18. Analysis of the trajectories of individual axons filled with horseradish peroxidase indicates that they branch into only one primary branch of the nerves to gluteus maximus, both in newborn and 14 day-old pups. The innervation of gluteus maximus at birth is essentially restricted to neuromuscular compartments. Synapse elimination probably plays a minor role in establishing neuromuscular compartments.

Recurrent dorsal root potentials and motoneuron morphology in the frog spinal cord

About one third of motoneurons stimulated intracellularly evoked dorsal root potentials (DRP) in the lumbar segments of the isolated and perfused frog spinal cord. Axon collaterals were found in one of the 22 motoneurons filled with HRP (horseradish peroxidase) through the stimulating electrode. In further experiments injecting individual motoneurons with cobalt, and filling the ventral roots with HRP or cobalt, the frequency of occurrence of axon collaterals was about 2% of the number of labelled motor cells. It is suggested that the presence of motor axon collaterals is not indispensable in the generation of the DRP evoked by ventral root or motor cell stimulation.

Evidence for restricted central convergence of cutaneous afferents on an excitatory reflex pathway to medial gastrocnemius motoneurons

1. We previously reported that excitatory postsynaptic potentials (EPSPs) produced by low-threshold electrical stimulation of the caudal cutaneous sural nerve (CCS) occur preferentially and with the shortest central latencies in the medial gastrocnemius (MG) portion of the triceps surae motor nuclei. The present study employs the spatial facilitation technique to assess interneuronal convergence on the short-latency excitatory pathway from CCS to MG by several other ipsilateral hindlimb afferents [the lateral cutaneous sural (LCS), caudal cutaneous femoral (CCF), saphenous (SAPH), superficial peroneal (SP), posterior tibial (TIB), and posterior articular (Joint) nerves]. 2. Spatial facilitation of CCF EPSPs in MG motoneurons was demonstrated with conditioning stimulation of the LCS, CCF, SAPH, SP, and TIB nerves, but was most readily and consistently observed with CCF conditioning. Facilitation of CCS and CCF EPSPs was obtained in individual MG motoneurons with a wide range of condition-test intervals. 3. CCF EPSPs in MG motoneurons produced by twice threshold (2T) afferent stimulation had a mean latency of 4.8 ms and often appeared as slowly rising, asynchronous potentials. On the other hand, 2T CCS EPSPs had a mean latency of 2.8 ms and appeared as sharper rising, less variable depolarizations. The optimum condition-test interval for facilitation of CCS and CCF EPSPs was found to be 5.2 ms on average, with CCS stimulation delayed from that of CCF. The longer latency of CCF EPSPs and the finding that the minimum condition-test interval was on the order of 3.9 ms suggests that convergence occurs late in the excitatory CCF pathway to MG motoneurons. 4. Convergence between excitatory pathways to MG from CCF and CCS afferents is discussed with regard to the original observations of Hagbarth on the location of cutaneous receptive fields and excitation of ankle extensors. In addition, evidence for the segregation of these specialized reflex pathways from those involved in general flexion reflexes is discussed.

Cholinergic activation of the lobster cardiac ganglion

The frequency of rhythmic burst activity of the isolated lobster cardiac ganglion is increased by exogenously applied acetylcholine and muscarinic agonists. Responses of individual motor neurons isolated from the ganglion by transection consist of a slow depolarization and repetitive bursting. The pharmacological profile of the receptors mediating this response is similar to that of vertebrate neuronal muscarinic receptors. Isolated ganglia incubated in the presence of [3H]-choline (18-19 h) exhibited radiolabelled acetylcholine accumulation. It is suggested that ganglionic excitation may be accomplished by extrinsic or intrinsic activation of muscarinic receptors on the motor neurons.

Fourier analysis of saccades in monkeys and humans

1. By recording eye movements with the search coil technique and subjecting them to an accurate infinite Fourier transform algorithm, we describe the Fourier spectra of human and monkey saccades. In both species we find heretofore undescribed features consisting of a regular pattern of local minima in the power plot, which cannot be attributed to noise. The frequency of these minima is well correlated with saccade duration. 2. Computer simulation shows that if the pulse component of the saccade is considered to be rectangular, then the first of these minima (called M1) occurs at a frequency that is the reciprocal of the duration of the pulse. 3. Comparing the position of this component during individual monkey saccades with electrophysiological recordings of motoneurons during the same saccades leads to the conclusion that these minima are related to the burst components in ocular motoneuron discharges. Specifically, the reciprocals of the frequencies of these minima are correlated with the duration of the burst component in the motoneuron discharge. 4. In the Fourier spectra of human saccades, the relationship of the frequency of M1 to saccadic duration is a function similar to that in the monkey. This adds to the evidence that the human saccade also is driven by a pulse-step signal. 5. In both monkeys and humans, T1, the reciprocal of the frequency of M1, is shorter than both the saccade duration and the burst duration of individual motoneurons, even though neurophysiological studies in monkeys generally report the saccadic burst duration to be equal to the saccade duration. This probably arises because the saccadic pulse is not rectangular, with the extremes contributing very little energy to the Fourier spectrum. By further computer modeling we show these shape effects explicitly: as the rise- and falltime increase, making the pulse less rectangular, T1 becomes shorter; in addition, as the asymmetry of rise and fall increases, the depth of the minima is reduced. We conclude that T1 measures the "effective pulse" duration of the motoneuron. 6. There is a difference in the relationship of effective pulse duration to the saccade duration between short and long saccades. For saccades shorter than approximately 40 ms in the human and 50 ms in the monkey, the pulse width as measured by this technique varies little with saccade duration. For longer saccades, effective pulse width increases linearly with duration. We agree with others that for short saccades the pulse is both height- and width-modulated; but for longer saccades, height modulation saturates and only width modulation remains.(ABSTRACT TRUNCATED AT 400 WORDS)

Morphological and quantal parameters of sensorimotor synapses in spinal cord isolated from infant rats

Structuro-functional correlations in the organization of connections between primary afferent fibers and motoneurons were investigated in the lumbar segments of spinal cord from 1–2-week-old rats. A single afferent fiber collateral was found to make contact with an individual motoneuron. There could be up to 10 boutons making contact. The n parameter of the binomial model was found to reflect numbers of contacts in the sensorimotor synapse. Analysis of sensorimotor EPSP by convolution of two binomial distributions revealed that neurotransmitter release sites differ in degree of probability (efficacy) of combined response to the arrival of nerve impulses.

Role of competition among sensory neurons in regulation of pattern of innervation at their central and peripheral targets.

1. The importance of competitive interactions among muscle sensory afferents on their projections to central and peripheral targets was studied by producing large reductions in the number of afferents during development. Removal of the brachial dorsal root ganglion (DRG2), which normally supplies the entire sensory innervation of the forelimb, in bullfrog (Rana catesbeiana) tadpoles caused a smaller number of neurons in the adjacent thoracic ganglion (DRG3) to sprout into the forelimb and into the brachial spinal cord. 2. Horseradish peroxidase labeling in postmetamorphic animals showed that DRG3 neurons innervating the triceps muscle arborize in a novel but now appropriate area of the spinal cord, the region containing motoneuronal dendrites. These foreign afferents do not arborize in inappropriate regions of the spinal gray matter, and their collaterals have the same rostrocaudal distribution as those of normal DRG2 muscle afferents. 3. After metamorphosis, the number of DRG3 sensory axons in individual triceps muscle nerves was determined. Normally, two-thirds of all triceps afferents project to the medial head alone, even though each of the three heads is of similar size and is contacted by similar numbers of motoneurons. After DRG2 removal, although the total number of DRG3 afferents projecting to the triceps muscle was smaller than normal, the medial head still received approximately two-thirds of the axons, just as in normal frogs. These results suggest that the proportional sensory innervation of the triceps muscle-heads is not dependent on competitive interactions among afferents. 4. DRG3 afferents projecting to the forelimb also sprouted to innervate appropriate brachial motoneurons. The average strength of connection between individual sensory and motor neurons was found to be the same as in normal animals, even though there was presumably more central target space available for each afferent axon. This suggests that the number and/or strength of central connections made by individual fibers may be an intrinsic property of muscle sensory neurons.

On the selectivity of intravenous μ‐ and κ‐opioids between nociceptive and non‐nociceptive reflexes in the spinalized rat

1. In electrophysiological experiments in spinalized, alpha-chloralose anaesthetized rats, opioids and anaesthetics were tested intravenously (i.v.) on the responses of individual motoneurones to alternating noxious (heat or pinch) and non-noxious (tap or vibration) stimuli. 2. On cells that were sensitive to low doses of mu-opioids, both fentanyl (0.5-4 micrograms kg-1 i.v.) and morphine (0.5 mg kg-1 i.v.) selectivity reduced reflexes to noxious stimuli to a greater degree than the higher doses required to reduce nociceptive reflexes (fentanyl 8 micrograms kg-1 i.v.; morphine 1-8 mg kg-1 i.v.) depressed non-nociceptive reflexes to a similar degree. 3. A similar spectrum of selectivity was seen with U-50,488 (0.5-16 mg kg-1 i.v.) although statistically significant selective depression of reflexes was only evident at the lowest dose tested (0.5 mg kg-1 i.v.). All effects of U-50,488 were readily reversed by low doses of the opioid antagonist, naloxone (10-100 micrograms kg-1 i.v.). 4. The dissociative anaesthetic/PCP ligand ketamine (0.5-4 mg kg-1 i.v.) was similar in having selective actions at low doses on sensitive cells but non-selective actions when higher doses were required. In contrast, the general anaesthetics methohexitone (4 mg kg-1 i.v.) and alphadolone/alphaxalone (1 mg kg-1 i.v.) were consistently non-selective between reflexes to noxious and non-noxious stimuli. alpha-Chloralose (20-40 mg kg-1 i.v.) had very little effect on reflexes to any of the synaptic inputs tested.