Voltage-sensitive ion channels in rhythmic motor systems

Voltage-sensitive ionic currents shape both the firing properties of neurons and their synaptic integration within neural networks that drive rhythmic motor patterns. Persistent sodium currents underlie rhythmic bursting in respiratory neurons. H-type pacemaker currents can act as leak conductances in spinal motoneurons, and also control long-term modulation of synaptic release at the crayfish neuromuscular junction. Calcium currents travel in rostro-caudal waves with motoneuron activity in the spinal cord. Potassium currents control spike width and burst duration in many rhythmic motor systems. We are beginning to identify the genes that underlie these currents.     

Generation of locomotion rhythms without inhibition in vertebrates: the search for pacemaker neurons

Locomotion rhythms are thought to be generated by neurons in the central-pattern-generator (CPG) circuit in the spinal cord. Synaptic connections in the CPG and pacemaker properties in certain CPG neurons, both may contribute to generation of the rhythms. In the half-center model proposed by Graham Brown a century ago, reciprocal inhibition plays a critical role. However, in all vertebrate preparations examined, rhythmic motor bursts can be induced when inhibition is blocked in the spinal cord. Without inhibition, neuronal pacemaker properties may become more important in generation of the rhythms. Pacemaker properties have been found in motoneurons and some premotor interneurons in different vertebrates and they can be dependent on N-Methyl-d-aspartate (NMDA) receptors (NMDAR) or rely on other ionic currents like persistent inward currents. In the swimming circuit of the hatchling Xenopus tadpole, there is substantial evidence that emergent network properties can give rise to swimming rhythms. During fictive swimming, excitatory interneurons (dINs) in the caudal hindbrain fire earliest on each swimming cycle and their spikes drive the firing of other CPG neurons. Regenerative dIN firing itself relies on reciprocal inhibition and background excitation. We now find that the activation of NMDARs can change dINs from firing singly at rest to current injection to firing repetitively at swimming frequencies. When action potentials are blocked, some intrinsic membrane potential oscillations at about 10 Hz are revealed, which may underlie repetitive dIN firing during NMDAR activation. In confirmation of this, dIN repetitive firing persists in NMDA when synaptic transmission is blocked by Cd(2+). When inhibition is blocked, only dINs and motoneurons are functional in the spinal circuit. We propose that the conditional intrinsic NMDAR-dependent pacemaker firing of dINs can drive the production of swimming-like rhythms without the participation of inhibitory neurotransmission.     

Differential contributions of somatic and dendritic calcium-dependent potassium currents to the control of motoneuron excitability following spinal cord injury

The hyperexcitability of alpha-motoneurons and accompanying spasticity following spinal cord injury (SCI) have been attributed to enhanced persistent inward currents (PICs), including L-type calcium and persistent sodium currents. Factors controlling PICs may offer new therapies for managing spasticity. Such factors include calcium-activated potassium (KCa) currents, comprising in motoneurons an after-hyperpolarization-producing current (I _KCaN) activated by N/P-type calcium currents, and a second current (I _KCaL) activated by L-type calcium currents (Li and Bennett in J neurophysiol 97:767–783, 2007). We hypothesize that these two currents offer differential control of PICs and motoneuron excitability based on their probable somatic and dendritic locations, respectively. We reproduced SCI-induced PIC enhancement in a two-compartment motoneuron model that resulted in persistent dendritic plateau potentials. Removing dendritic I _KCaL eliminated primary frequency range discharge and produced an abrupt transition into tertiary range firing without significant changes in the overall frequency gain. However, I _KCaN removal mainly increased the gain. Steady-state analyses of dendritic membrane potential showed that I _KCaL limits plateau potential magnitude and strongly modulates the somatic injected current thresholds for plateau onset and offset. In contrast, I _KCaN had no effect on the plateau magnitude and thresholds. These results suggest that impaired function of I _KCaL may be an important intrinsic mechanism underlying PIC-induced motoneuron hyperexcitability following SCI.     

A large-scale model of some spinal reflex circuits

This paper reports the development of a large-scale model of some spinal reflex circuitry, useful for studying the dynamic interactions among neuronal populations during simple behaviors. The included populations and properties of the neurons and terminals were derived from the literature, mainly on cat spinal cord. The model was conceived as a symmetrical controller of a pair of antagonistic muscles, within the behavioral domain of the stretch and Golgi-tendon-organ reflexes, and was scaled to include realistic numbers of motoneurons. Inputs to the model were fiber populations providing random synaptic drive to some of the populations and sensory stimuli appropriate for the reflexes. The resulting model contained roughly 2300 neurons in six pairs of populations. The total number of connections in the model was about 600 000, and individual postsynaptic potentials were small (0.1–0.6 mV). Model responses were calibrated by examination of their ability to reproduce known aspects of the reflexes. Published algorithms were used to construct the environment, which is easily expandable, in terms of membrane channels, neuronal geometry, and synaptic properties. The system was built to combine a system-level perspective of spinal circuitry with the single-unit perspective common in electrophysiological investigation. It provides a computational tool for system-level investigations of spinal cord similar to the tools available at the level of membrane currents. Received: 16 May 1997 / Accepted in revised form: 2 October 1997     

Suppressing the excitability of spinal motoneurons by extracellularly applied electrical fields: insights from computer simulations.

The effect of extracellularly applied electrical fields on neuronal excitability and firing behavior is attributed to the interaction between neuronal morphology and the spatial distribution and level of differential polarization induced by the applied field in different elements of the neuron. The presence of voltage-gated ion channels that mediate persistent inward currents (PICs) on the dendrites of spinal motoneurons enhances the influence of electrical fields on the motoneuronal firing behavior. The goal of the present study was to investigate, with a realistic motoneuron computer model, the effects of extracellularly applied electrical fields on the excitability of spinal motoneurons with the aim of reducing the increased motoneuronal excitability after spinal cord injury (SCI). Our results suggest that electrical fields could suppress the excitability of motoneurons and reduce their firing rate significantly by modulating the magnitude of their dendritic PIC. This effect was achieved at different field directions, intensities, and polarities. The reduction in motoneuronal firing rate resulted from the reduction in the magnitude of the dendritic PIC reaching the soma by the effect of the applied electrical field. This reduction in PIC was attributed to the dendritic field-induced differential polarization and the nonlinear current-voltage relationship of the dendritic PIC-mediating channels. Because of the location of the motoneuronal somata and initial segment with respect to the dendrites, these structures were minimally polarized by the applied field compared with the extended dendrites. In conclusion, electrical fields could be used for suppressing the hyperexcitability of spinal motoneurons after SCI and reducing the level of spasticity.     

Development of spinal motor networks in the chick embryo.

We have examined the cellular and synaptic mechanisms underlying the genesis of alternating motor activity in the developing spinal cord of the chick embryo. Experiments were performed on the isolated lumbosacral cord maintained in vitro. Intracellular and whole cell patch clamp recordings obtained from sartorius (primarily a hip flexor) and femorotibialis (a knee extensor) motoneurons showed that both classes of cell are depolarized simultaneously during each cycle of motor activity. Sartorius motoneurons generally fire two bursts/cycle, whereas femorotibialis motoneurons discharge throughout their depolarization, with peak activity between the sartorius bursts. Voltage clamp recordings revealed that inhibitory and excitatory synaptic currents are responsible for the depolarization of sartorius motoneurons, whereas femorotibialis motoneurons are activated principally by excitatory currents. Early in development, the dominant synaptic currents in rhythmically active sartorius motoneurons appear to be inhibitory so that firing is restricted to a single, brief burst at the beginning of each cycle. In E7-E13 embryos, lumbosacral motor activity could be evoked following stimulation in the brainstem, even when the brachial and cervical cord was bathed in a reduced calcium solution to block chemical synaptic transmission. These findings suggest that functional descending connections from the brainstem to the lumbar cord are present by E7, although activation of ascending axons or electrical synapses cannot be eliminated. Ablation, optical, and immunocytochemical experiments were performed to characterize the interneuronal network responsible for the synaptic activation of motoneurons. Ablation experiments were used to show that the essential interneuronal elements required for the rhythmic alternation are in the ventral part of the cord. This observation was supported by real-time Fura-2 imaging of the neuronal calcium transients accompanying motor activity, which revealed that a high proportion of rhythmically active cells are located in the ventrolateral part of the cord and that activity could begin in this region. The fluorescence transients in the majority of neurons, including motoneurons, occurred in phase with ventral root or muscle nerve activity, implying synchronized neuronal action in the rhythm generating network. Immunocytochemical experiments were performed in E14-E16 embryos to localize putative inhibitory interneurons that might be involved in the genesis or patterning of motor activity. The results revealed a pattern similar to that seen in other vertebrates with the dorsal horn containing neurons with gamma-aminobutyric acid (GABA)-like immunoreactivity and the ventral and intermediate regions containing neurons with glycine-like immunoreactivity.     

Measurement and nature of firing rate adaptation in turtle spinal neurons

There is sparse literature on the profile of action potential firing rate (spike-frequency) adaptation of vertebrate spinal motoneurons, with most of the work undertaken on cells of the adult cat and young rat. Here, we provide such information on adult turtle motoneurons and spinal ventral-horn interneurons. We compared adaptation in response to intracellular injection of 30-s, constant-current stimuli into high-threshold versus low-threshold motoneurons and spontaneously firing versus non-spontaneously-firing interneurons. The latter were shown to possess some adaptive properties that differed from those of motoneurons, including a delayed initial adaptation and more predominant reversal of adaptation attributable to plateau potentials. Issues were raised concerning the interpretation of changes in the action potentials afterhyperpolarization shape parameters throughout spike-frequency adaptation. No important differences were demonstrated in the adaptation of the two motoneuron and two interneuron groups. Each of these groups, however, was modeled by its own unique combination of action potential shape parameters for the simulation of its 30-s duration of spike-frequency adaptation. Also, for a small sample of the very highest-threshold versus lowest-threshold motoneurons, the former group had significantly more adaptation than the latter. This finding was like that shown previously for cat motoneurons supplying fast- versus slow twitch motor units.     

Progesterone neuroprotection in spinal cord trauma involves up-regulation of brain-derived neurotrophic factor in motoneurons

Progesterone (PROG) provides neuroprotection to the injured central and peripheral nervous system. These effects may be due to regulation of myelin synthesis in glial cells and also to direct actions on neuronal function. Both types of cells express classical intracellular PROG receptors (PR), while neurons additionally express the PROG membrane-binding site called 25-Dx. In motoneurons from rats with spinal cord injury (SCI), PROG restores to normal the deficient levels of choline acetyl-transferase and of alpha3 subunit Na,K-ATPase mRNA, while levels of the growth associated protein GAP-43 mRNA are further stimulated. Recent studies suggest that neurotrophins are possible mediators of hormone action, and in agreement with this assumption, PROG treatment of rats with SCI increases the expression of brain-derived neurotrophic factor (BDNF) at both the mRNA and protein levels in ventral horn motoneurons. In situ hybridization (ISH) has shown that SCI reduces BDNF mRNA levels by 50% in spinal motoneurons, while PROG administration to injured rats (4mg/kg/day during 3 days, s.c.) elicits a three-fold increase in grain density. In addition to enhancement of mRNA levels, PROG increases BDNF immunoreactivity in perikaryon and cell processes of motoneurons of the lesioned spinal cord, and also prevents the lesion-induced chromatolytic degeneration of spinal cord motoneurons as determined by Nissl staining. Our findings strongly indicate that motoneurons of the spinal cord are targets of PROG, as confirmed by the expression of PR and the regulation of molecular parameters. PROG enhancement of endogenous neuronal BDNF could provide a trophic environment within the lesioned spinal cord and might be part of the PROG activated-pathways to provide neuroprotection. Thus, PROG treatment constitutes a new approach to sustain neuronal function after injury.     

Effect of calcium deficiency and addition of calcium antagonists on motoneuron synaptic potentials of isolated Emys orbicularis turtle spinal cord

In experiments carried out on the isolated spinal cord of the tortoise Emys orbicularis postsynaptic potentials produced in spinal motoneurons by stimulation of the descending tracts and dorsal roots were investigated by means of the intracellular recording technique. Postsynaptic potentials were completely and reversibly blocked in Ca2+-free solutions containing 5.0 mM Mg2+ or 2.0 mM Mn2+. The amplitude and frequency of spontaneous synaptic potentials were also reduced under these conditions. The effect of Ca2+-free medium indicates that the synaptic transmission in these synapses is mediated by chemical mechanism.     

Structure of allotransplanted ganglia and regenerated neuromuscular connections in crayfish

In adult crayfish, Procambarus clarkii, motoneurons to a denervated abdominal superficial flexor muscle regenerate long-lasting and highly specific synaptic connections as seen from recordings of excitatory postsynaptic potentials, even when they arise from the ganglion of another crayfish. To confirm the morphological origins of these physiological connections we examined the fine structure of the allotransplanted tissue that consisted of the third abdominal ganglion and the nerve to the superficial flexor muscle (the fourth ganglion and the connecting ventral nerve cord were also included). Although there is considerable degeneration, the allotransplanted ganglia display intact areas of axon tracts, neuropil, and somata. Thus in both short (6–8 weeks) and long (24–30 weeks) term transplants approximately 20 healthy somata are present and this is more than the five axons regenerated to the host muscle. The principal neurite and dendrites of these somata receive both excitatory and inhibitory synaptic inputs, and these types of synaptic contacts also occur among the dendritic profiles of the neuropil. Axon tracts in the allotransplanted ganglia and ventral nerve cord consist largely of small diameter axons; most of the large axons including the medial and lateral giant axons are lost. The transplanted ganglia have many blood vessels and blood lacunae ensuring long-term survival. The transplanted superficial flexor nerve regenerates from the ventral to the dorsal surface of the muscle where it has five axons, each consisting of many profiles rather than a single profile. This indicates sprouting of the individual axons and accounts for the enlarged size of the regenerated nerve. The regenerated axons give rise to normal-looking synaptic terminals with well-defined synaptic contacts and presynaptic dense bars or active zones. Some of these synaptic terminals lie in close proximity to degenerating terminals, suggesting that they may inhabit old sites and in this way ensure target specificity. The presence of intact somata, neuropil, and axon tracts are factors that would contribute to the spontaneous firing of the transplanted motoneurons. © 1996 John Wiley & Sons, Inc.     

Modelling Feedback Excitation,Pacemaker Properties and Sensory Switching of Electrically Coupled Brainstem Neurons Controlling Rhythmic Activity

What cellular and network properties allow reliable neuronal rhythm generation or firing that can be started and stopped by brief synaptic inputs? We investigate rhythmic activity in an electrically-coupled population of brainstem neurons driving swimming locomotion in young frog tadpoles, and how activity is switched on and off by brief sensory stimulation. We build a computational model of 30 electrically-coupled conditional pacemaker neurons on one side of the tadpole hindbrain and spinal cord. Based on experimental estimates for neuron properties, population sizes, synapse strengths and connections, we show that: long-lasting, mutual, glutamatergic excitation between the neurons allows the network to sustain rhythmic pacemaker firing at swimming frequencies following brief synaptic excitation; activity persists but rhythm breaks down without electrical coupling; NMDA voltage-dependency doubles the range of synaptic feedback strengths generating sustained rhythm. The network can be switched on and off at short latency by brief synaptic excitation and inhibition. We demonstrate that a population of generic Hodgkin-Huxley type neurons coupled by glutamatergic excitatory feedback can generate sustained asynchronous firing switched on and off synaptically. We conclude that networks of neurons with NMDAR mediated feedback excitation can generate self-sustained activity following brief synaptic excitation. The frequency of activity is limited by the kinetics of the neuron membrane channels and can be stopped by brief inhibitory input. Network activity can be rhythmic at lower frequencies if the neurons are electrically coupled. Our key finding is that excitatory synaptic feedback within a population of neurons can produce switchable, stable, sustained firing without synaptic inhibition.     

Modulation of motoneuronal firing behavior after spinal cord injury using intraspinal microstimulation current pulses: a modeling study.

We simulated the effects of delivering focal electrical stimuli to the central nervous system to modulate the firing rate of neurons and alleviate motor disorders. Application of these stimuli to the spinal cord to reduce the increased excitability of motoneurons and resulting spasticity after spinal cord injury (SCI) was examined by means of a morphologically detailed computer model of a spinal motoneuron. High-frequency sinusoidal and rectangular pulses as well as biphasic charge-balanced and charge-imbalanced pulses were examined. Our results suggest that suprathreshold high-frequency sinusoidal or rectangular current pulses could inactivate the Na+ channels in the soma and initial segment, and block action potentials from propagating through the axon. Subthreshold biphasic charge-imbalanced pulses reduced the motoneuronal firing rate significantly (up to approximately 25% reduction). The reduction in firing rate was achieved through stimulation-induced hyperpolarization generated in the first node of Ranvier. Because of their low net DC current, these pulses could be tolerated safely by the tissue. To deliver charge-imbalanced pulses with the lowest net DC current and induce the largest reduction in motoneuronal firing rate, we studied the effect of various charge-imbalanced pulse parameters. Short pulse durations were found to induce the largest reduction in firing rate for the same net DC level. Subthreshold high-frequency sinusoidal and rectangular current pulses and low-frequency biphasic charge-balanced pulses, on the other hand, were ineffective in reducing the motoneuronal firing rate. In conclusion, the proposed electrical stimulation paradigms could provide potential rehabilitation interventions for suppressing the excitability of neurons to reduce the severity of motor disorders after injury to the central nervous system.     

Synaptic integration in spinal motoneurones.

Spinal motoneurones receive thousands of presynaptic excitatory and inhibitory synaptic contacts distributed throughout their dendritic trees. Despite this extensive convergence, there have been very few studies of how synaptic inputs interact in mammalian motoneurones when they are activated concurrently. In the experiments reported here, we measured the effective synaptic currents and the changes in firing rate evoked in cat spinal motoneurones by concurrent repetitive activation of two separate sets of presynaptic neurons. We compared these effects to those predicted by a linear sum of the effects produced by activating each set of presynaptic neurons separately. We generally found that when two inputs were activated concurrently, both the effective synaptic currents and the synaptically-evoked changes in firing rate they produced in motoneurones were generally linear, or slightly less than the linear sum of the effects produced by activating each input alone. The results suggest that the spatial distribution synaptic terminals on the dendritic trees of motoneurones may help isolate synapses from one another, minimizing non-linear interactions.     

A minimal,compartmental model for a dendritic origin of bistability of motoneuron firing patterns

Various nonlinear regenerative responses, including plateau potentials and bistable repetitive firing modes, have been observed in motoneurons under certain conditions. Our simulation results support the hypothesis that these responses are due to plateau-generating currents in the dendrites, consistent with a major role for a noninactivating calcium L-type current as suggested by experiments. Bistability as observed in the soma of low- and higher-frequency spiking or, under TTX, of near resting and depolarized plateau potentials, occurs because the dendrites can be in a near resting or depolarized stable steady state. We formulate and study a two-compartment minimal model of a motoneuron that segregates currents for fast spiking into a soma-like compartment and currents responsible for plateau potentials into a dendrite-like compartment. Current flows between compartments through a coupling conductance, mimicking electrotonic spread. We use bifurcation techniques to illuminate how the coupling strength affects somatic behavior. We look closely at the case of weak coupling strength to gain insight into the development of bistable patterns. Robust somatic bistability depends on the electrical separation since it occurs only for weak to moderate coupling conductance. We also illustrate that hysteresis of the two spiking states is a natural consequence of the plateau behavior in the dendrite compartment.     

Electrical synapses between motoneurons in the spinal cord of the newborn rat

Ventral roots of the newborn rat spinal cord were stimulated while recording intracellularly from motoneurons. In many cells, stimulation subthreshold for an antidromic action potential in the impaled cell produced a small, short-latency depolarization, which was unaffected by membrane polarization. This response (antidromic synaptic potential, a.s.p.) was also seen, in some cells, on stimulating the ventral root of an adjacent segment. Replacement of Ca2+ (2 mM) with Mn2+ (3 mM) or Mg2+ (10 mM) completely abolished orthodromic synaptic potentials, but the a.s.p. persisted. These results strongly suggest that the a.s.p. is produced by an electrical interaction between motoneurons.     

Inhibitory miniature synaptic potentials in rat motoneurons

In the newborn rat spinal cord, spontaneous potentials were recorded, with KCl electrodes, from motoneurons in the presence of tetrodotoxin (10(-6) g ml-1) to abolish nerve impulses. These potentials occurred at low frequencies (less than 2 Hz), and their mean amplitude was a fraction of 1 mV. An increase of osmolarity with sucrose or an increase of extracellular K+, increased the frequency of miniature synaptic potentials. The amplitude of the spontaneous potentials was increased by intracellular injection of Cl-. Strychnine (2-25 microM) completely abolished the spontaneous potentials. It is suggested that these potentials are produced by the spontaneous release of packages of inhibitory transmitter at synapses on motoneurons.     

Coerulospinal enhancement of repetitive firing with correlative changes in postspike afterhyperpolarization of cat spinal motoneurons

The present study was aimed at determining if inputs from the locus coeruleus (LC) have any effect on repetitive firing of ventral horn motoneurons in cats. In hindlimb flexor and extensor motoneurons stimulated intrasomatically with current below the threshold for repetitive discharges, added LC-evoked excitatory post-synaptic potentials (EPSPs) were consistently found to produce repetitive firing, suggesting a lowering in the repetitive firing threshold attributable to excitatory LC inputs. With those extensor motoneurons showing episodic, self-sustained firing, LC-EPSPs introduced during the quiescent period were capable of starting a continuous discharge with rhythmic frequencies higher than the spontaneous activity. In some of these cells, intracellularly applied hyperpolarizing current was able to stop the spontaneous discharges. Subsequently, LC stimuli were found to reinitiate repetitive discharges, thus counteracting the ongoing suppression of the motoneurons. Quantitative analysis of the single-spike afterhyperpolarization (AHP) indicated a consistent reduction in its amplitude and time course (duration, time-to-peak, half-decay time) for flexor and extensor motoneurons in response to LC conditioning stimuli. Present results suggest an excitatory LC action on the repetitive discharges of cat motoneurons accompanied by a concurrent decrease in the amplitude and time course of the single-spike AHPs.     

Synaptic connections in a dissociated mixed culture of rat dorsal root ganglion and spinal cord neurons

Postsynaptic currents and action potentials recorded from neurons in a mixed culture of rat dorsal root ganglion and spinal cord cells are described. The existence of mutual synaptic connections between the above two types of neurons is demonstrated. Neirofiziologiya/Neurophysiology, Vol. 38, No. 4, pp. 358–360, July–August, 2006.     

Work organization of a group of human motoneurons during voluntary muscular contraction

Needle electrodes were used to record action potentials of motor units of the rectus femoris muscle during isometric contraction (up to 50% of maximal). Up to 10 motor units working simultaneously could be identified. Under strictly stable conditions of muscular contraction the recruitment order of the motoneurons was constant. The firing rate was inversely proportional as a rule to this recruitment order. As a rule the changes in frequency connected with voluntary contraction of measured strength were in the same direction for different motoneurons. Statistical analysis of the frequency fluctuations observed during contraction of constant strength revealed direct correlation between them. The behavior of the motoneurons as described above is regarded as the result of the diffuse, indeterminate distribution of the synaptic input in the group of motoneurons innervating the muscle studied. It was also shown that even under stable conditions individual motoneurons or groups of them sometimes fired independently. During the performance of different types of movements, the firing rates of the recruited motoneurons varied in different directions and some motoneurons were replaced by others. This shows that when motoneurons function under natural conditions they use not only a common (indeterminate) but also a determinate input.Institute of Problems of Information Transmission, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 5, No. 1, pp. 77–87, January–February, 1973.     

Monoaminergic Modulation of Spinal Viscero-Sympathetic Function in the Neonatal Mouse Thoracic Spinal Cord

Descending serotonergic, noradrenergic, and dopaminergic systems project diffusely to sensory, motor and autonomic spinal cord regions. Using neonatal mice, this study examined monoaminergic modulation of visceral sensory input and sympathetic preganglionic output. Whole-cell recordings from sympathetic preganglionic neurons (SPNs) in spinal cord slice demonstrated that serotonin, noradrenaline, and dopamine modulated SPN excitability. Serotonin depolarized all, while noradrenaline and dopamine depolarized most SPNs. Serotonin and noradrenaline also increased SPN current-evoked firing frequency, while both increases and decreases were seen with dopamine. In an in vitro thoracolumbar spinal cord/sympathetic chain preparation, stimulation of splanchnic nerve visceral afferents evoked reflexes and subthreshold population synaptic potentials in thoracic ventral roots that were dose-dependently depressed by the monoamines. Visceral afferent stimulation also evoked bicuculline-sensitive dorsal root potentials thought to reflect presynaptic inhibition via primary afferent depolarization. These dorsal root potentials were likewise dose-dependently depressed by the monoamines. Concomitant monoaminergic depression of population afferent synaptic transmission recorded as dorsal horn field potentials was also seen. Collectively, serotonin, norepinephrine and dopamine were shown to exert broad and comparable modulatory regulation of viscero-sympathetic function. The general facilitation of SPN efferent excitability with simultaneous depression of visceral afferent-evoked motor output suggests that descending monoaminergic systems reconfigure spinal cord autonomic function away from visceral sensory influence. Coincident monoaminergic reductions in dorsal horn responses support a multifaceted modulatory shift in the encoding of spinal visceral afferent activity. Similar monoamine-induced changes have been observed for somatic sensorimotor function, suggesting an integrative modulatory response on spinal autonomic and somatic function.