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The external urethral sphincter motoneurons in the sacral ventral horn control the striated external urethral sphincter muscles that circle the urethra. Activity in these motoneurons and muscle normally contribute to continence but during micturition, when urine must pass through the urethra, the motoneurons and striated muscle must be silenced. Following injury to descending pathways in the spinal cord, the ability to inhibit sphincter activity is disrupted or lost, resulting in bladder-sphincter dyssynergia and functional obstruction of the urethra during voiding. This chapter will first review the various reflex pathways and neuronal properties that contribute to continence, and which must be modulated during micturition in the spinal intact animal. A discussion about how the dyssynergia seen with spinal cord injury may be produced will then be presented.

Whole-cell patch recordings were made from parasympathetic preganglionic neurones (P-PGNs) and unidentified intermediolateral (IML) neurones in thick slices of the lower lumbar and sacral spinal cord of 14- to 21-day-old rats. The P-PGNs and IML neurones examined were similar in terms of soma sizes, input resistance and capacitance, and displayed a sag conductance as well as rebound firing. In the absence of drugs, the neurones responded with either tonic or adapting firing to depolarizing current steps. However, in the presence of the group I metabotropic glutamate receptor agonist (RS)-3,5-dihydroxyphenylglycine (DHPG), almost half of the neurones displayed accelerating firing rates during the constant current injection, followed by a sustained after-discharge. In the presence of TTX, plateau potentials were observed. The firing changes and plateaux were blocked by nifedipine, an L-type Ca2+ channel blocker, and (S)-(-)-Bay K8644 was able to produce these firing changes and plateaux in the absence of DHPG, demonstrating the involvement of an L-type Ca2+ conductance. Ca2+-activated nonspecific cationic conductances also appear to contribute to the firing changes. A few neurones displayed membrane oscillations and burst firing in the presence of DHPG. The results suggest that the firing characteristics of both P-PGNs and other neurones likely to be involved in caudal spinal reflex control are not static but, rather, quite dynamic and under metabotropic glutamate receptor modulatory control. Such changes in firing patterns may be involved in normal pelvic parasympathetic reflex function during micturition, defaecation and sexual reflexes, and may contribute to the abnormal output patterns seen with loss of descending brainstem input and visceral or perineal sensory disturbances.

The excitability of two groups of neurones located in different parts of the sacral spinal cord were examined during micturition in decerebrate adult cats. One group of cells, characterized by their activation by pudendal cutaneous afferents, was located in the dorsal commissure of the first and second sacral spinal segments. The second group, located in the dorsal horn of the first sacral spinal segment, was excited by group II muscle and cutaneous afferents. Micturition was evoked by distension of the urinary bladder or by electrical stimulation of the pontine micturition centre. Tonic firing was induced in the neurones by ejection of DL-homocysteic acid from the recording extracellular micropipette. The instantaneous firing frequency of 11/17 sacral dorsal grey commissure neurones was decreased from 7 to 100 % during micturition, and on average was about half of the prevoid firing frequency. It is hypothesized that these sacral neurones are interposed in polysynaptic excitatory pathways from sacral perineal afferents to sphincter motoneurones and that they are subject to direct postsynaptic inhibition during micturition. One other cell showed no change in firing during micturition, two displayed complex patterns of modulation, while 3/17 of the dorsal grey commissure neurones increased their firing rate 30 to 1000 % during micturition. It is hypothesized that the excited neurones may be part of the inhibitory pathways mediating postsynaptic inhibition of sphincter motoneurones or sacral primary afferent depolarization during micturition. Alternatively, they may be part of the excitatory urethral-bladder reflex circuitry. A small (5-15 %) but significant decrease in firing was observed in 4/5 of the group II rostral sacral neurones examined; the firing of a fifth neurone was unchanged. The depression of group II neurones may serve to suppress unwanted hindlimb reflexes that could disrupt micturition.

The storage and elimination of urine requires the coordination of activity between the autonomic nervous system (thoracolumbar sympathetic and sacral parasympathetic divisions) controlling the urinary bladder and urethra and the lumbosacral somatic motoneurons innervating the striated sphincter and pelvic floor muscles. These three efferent systems involved in the control of lower urinary tract function receive segmental sensory information from various visceral organs and the perineum, as well as inputs from supraspinal regions. Ascending and descending connections between the various spinal segments levels and supraspinal regions provide the reflex substrates participating in normal bladder continence and micturition reflexes. Many of the actions of descending and segmental reflexes are mediated by excitatory and inhibitory sacral spinal interneurons located within the region of the parasympathetic preganglionic autonomic neurons and the sphincter ventral horn motoneurons. This review will: (1) discuss the basic organization and spinal elements of the reflex pathways subserving continence and micturition; (2) describe features of the identified sacral interneuronal circuitry contributing to the control of the bladder and sphincter function; and (3) discuss how changes in the control of these reflex pathways and neurons may contribute to abnormal patterns of bladder and sphincter function commonly observed following spinal cord injury.

Normally, during bladder filling (continence) and expulsion (micturition) there is a reciprocity between the pattern of activity in the urinary bladder sacral parasympathetic efferents and the somatic motoneurones innervating the striated external urethral sphincter muscle. The co-ordination of this pattern of reciprocal activity appears to be determined by excitatory and inhibitory actions of a variety of segmental afferents and descending systems with sacral spinal actions. These actions may in part be mediated through lower lumbar and sacral excitatory and inhibitory spinal interneurones. Over the past 30 years, both neuroanatomical and electrophysiological approaches have been used to reveal an ever-increasing richness in the neuronal network in the lower spinal cord related to the bladder and striated external urethral sphincter muscle. The purpose of this review is to present an overview of the identified excitatory and inhibitory spinal interneurones hypothesized to be involved in the central networks controlling the sacral bladder parasympathetic preganglionic neurones and striated urethral sphincter motoneurones during continence and micturition.

1. Responses to pudendal afferent stimulation and depolarizing intracellular current injection were examined in sacral sphincter motoneurones in decerebrate cats. 2. In 16 animals examined, 2-10 s trains of electrical stimulation of pudendal afferents evoked sustained sphincter motoneurone activity lasting from 5 to >50 s after stimulation. The sustained response was observed in: 11 animals in the absence of any drugs; two animals after the intravenous administration of 5-hydroxytryptophan (5-HTP; <= 20 mg kg-1); one animal in which methoxamine was perfused onto the ventral surface of the exposed spinal cord; and two animals following the administration of intravenous noradrenergic agonists. 3. Extracellular and intracellular recordings from sphincter motoneurones revealed that the persistent firing evoked by afferent stimulation could be terminated by motoneurone membrane hyperpolarization during micturition or by intracellular current injection. 4. Intracellular recordings revealed that 22/40 sphincter motoneurones examined displayed a non-linear, steep increase in the membrane potential in response to depolarizing ramp current injection. The mean voltage threshold for this non-linear membrane response was -43 +/- 3 mV. Five of the 22 cells displaying the non-linear membrane response were recorded prior to the administration of 5-HTP; 17 after the intravenous administration of 5-HTP (<= 20 mg kg-1). 5. It is concluded that sphincter motoneurones have a voltage-sensitive, non-linear membrane response to depolarization that could contribute to sustained sphincter motoneurone firing during continence.

1. Monosynaptic extracellular field potentials evoked by electrical stimulation of ipsilateral hindlimb nerves carrying muscle group I, II and cutaneous afferents were examined during fictive locomotion. Fifty-eight field potentials were recorded in the dorsal and intermediate laminae throughout the mid-lumbar to first sacral segments and fictive locomotion was evoked by mesencephalic locomotor region (MLR) stimulation in paralysed decerebrate cats. 2. The majority (96 %) of group I, II and cutaneous-evoked field potentials were decreased during fictive locomotion. Group I, cutaneous and dorsal group II potentials were reduced on average to about 80 % of control values. Group II field potentials recorded in the intermediate laminae were reduced to a mean of 49 % of control values. Cyclic variations in field potential amplitude between the flexion and extension phases were observed in 24 of 45 cases analysed. Of those 24 field potentials, the two group I and four cutaneous field potentials were smaller during the flexion phase. All eleven group II and the remaining seven cutaneous fields were smaller during extension. In all but two cases, these cyclic variations were smaller than the tonic depression upon which they were superimposed. 3. In 7/9 group II field potentials examined, reductions (on average to 85 % of control) began with the onset of MLR stimulation that produced tonic activity in the motor nerves before the onset of rhythmic alternating, locomotor discharges. In six of the seven cases the field potential depression increased with the establishment of fictive locomotion. This observation and the cyclic modulation of field potentials during fictive locomotion suggests that the depression was strongly linked to the operation of the spinal locomotor circuitry. 4. Depression of the monosynaptic components of the field potentials suggests a reduction in synaptic transmission from primary afferents to first-order spinal interneurones during fictive locomotion. Accordingly, the larger depression of intermediate group II field potentials may indicate a preferential reduction in transmission from group II afferents to interneurones located in intermediate spinal laminae. 5. Flexion reflexes evoked by group II and cutaneous afferents were also depressed during MLR-evoked fictive locomotion. The possibility that this depression results from a reduction in transmission from primary afferents, and in particular from group II afferents, ending on interneurones in the intermediate laminae is discussed.

1. Excitability changes in afferents innervating the urethra, perineum and hindlimb were measured in decerebrated cats during micturition and in response to stimulation of lumbosacral afferents. Increases in excitability were interpreted as primary afferent depolarization (PAD) and decreases as primary afferent hyperpolarization. 2. Excitability increases were observed in 11 of 19 urethral pudendal afferents during micturition. Four of these 11 afferents showed an excitability increase during voiding. Seven of these showed a biphasic change with a decrease in excitability when sphincter activity resumed at the end of the void. Three of 19 afferents showed an excitability decrease during micturition and no change was detected in five afferents. 3. During micturition, the peak amplitude of urethral afferent-evoked excitatory postsynaptic potentials in seven of eight sphincter motoneurones was diminished to a mean of 36% of control values. 4. Eighty per cent of hindlimb cutaneous afferents and 50% of dorsal penile/clitoral and superficial perineal nerve afferents in the sacral cord showed increased excitability during voiding. No excitability increases were measured in 13 hindlimb cutaneous fibres examined in the lumbar segments. 5. PAD was observed in sacral urethral, perineal and hindlimb cutaneous afferents in response to electrical stimulation of other perineal, urethral, hindlimb cutaneous and group II muscle afferents. 6. It is concluded that control of transmission from urethral afferents by the micturition circuitry is different to that by sensory transmission from hindlimb and perineal regions during micturition. We hypothesize that more than one population of sacral PAD-mediating interneurones is involved.

Micturition in the decerebrate cat is characterized by a coordinated bladder contraction and a simultaneous decrease in external urethral sphincter (EUS) efferent activity. Without the suppression of EUS activity, voiding is significantly impaired, resulting in a state sometimes referred to as bladder-sphincter dyssynergia. The aim of the present study was to determine whether glycinergic inhibition contributes to the suppression of EUS activity during micturition evoked by bladder distension or electrical stimulation of the pontine micturition center (PMC) in decerebrate cats. Using subconvulsive intravenous doses of strychnine (0.1-0.24 mg/kg), we examined changes in bladder and EUS electroneurographic (ENG) activity during micturition. Following subconvulsive doses of strychnine, tonic EUS ENG activity increased during bladder filling in five of six animals. In the presence of strychnine, it was possible to evoke reflex bladder contractions of similar duration and peak pressure to those observed before strychnine administration. However, there was an absence of suppression of EUS ENG activity during the bladder contractions in all the animals. To determine whether the changes in sphincter activity could be due to strychnine acting at glycine receptors on EUS motoneurons, sacral spinal tissue was processed for a structural protein (gephyrin) associated with the glycine receptor. Motoneurons in Onufs nucleus in S1 were identified using choline acetyltransferase immunohistochemistry and subsequently processed with a gephyrin monoclonal antibody. Abundant gephyrin labeling was evident throughout Onufs nucleus. Since Onufs nucleus is made up of EUS and other motoneuron populations, a sample of antidromically identified urethral and anal sphincter motoneurons were intracellularly labeled with tetramethylrhodamine dextran (TMR-D) and then processed with the gephyrin antibody. Using dual-beam confocal microscopy, gephyrin immunoreactivity was observed on the soma and proximal processes of individual EUS motoneurons in both male and female animals. It was concluded that a strychnine-sensitive mechanism contributes to the suppression of sphincter activity normally observed during voiding. Although glycinergic inhibition may affect several components of the circuitry responsible for micturition, it appears that the suppression of EUS motoneurons during micturition may be partly due to a direct glycinergic inhibition of the EUS motoneurons.

Electrical stimulation of the urethral sensory pudendal nerve in decerebrate or acute spinal cats was used to evoke micturition reflexes in animals that failed to respond to bladder distension. In the decerebrate animals, stimulation of urethral afferents evoked voiding characterized by a large bladder pressure increase coordinated with a simultaneous decrease in external urethral sphincter activity. In animals in which the spinal cord was transected between T10 and L6, electrical stimulation of the urethral afferents evoked small increases in bladder pressure that were insufficient to expel fluid but the contractions were coordinated with a decrease in external urethral sphincter activity. It was concluded that in addition to interacting with spinobulbospinal micturition pathways, urethral pudendal afferents may have direct access to a spinal circuitry that can coordinate bladder and sphincter activity.

Thyrotropin-releasing hormone (TRH) has been recognized as a neuromodulator in several CNS regions, including the thoracolumbar spinal cord where an influence on cardiovascular autonomic function has been proposed. To identify the cellular mechanisms involved in the latter, whole cell patch-clamp recordings were obtained from 52 thoracolumbar lateral horn cells, including 17 sympathetic preganglionic neurons (SPNs), in spinal cord slices from neonatal rat (11-21 days). Under current clamp, bath applications of TRH (1-20 microM) induced a slowly rising and prolonged membrane depolarization in eight of nine cells tested. Under voltage clamp (holding potential -65 mV), 33 of 37 tested cells displayed a TRH-induced, tetrodotoxin-resistant inward current that was associated with either a reduction or an increase in membrane ion conductances. Current-voltage (I-V) relationships in 28 cells suggested two conductances. In 9 cells the current reversed at about -107 mV; in 10 cells the I-V lines remained parallel, whereas in 9 cells the current reversed at around -40 mV. In three of three cells, addition of 2 mM barium was associated with an inward current, and the TRH-induced inward current was also suppressed, suggesting the presence of a resting barium- and TRH-sensitive potassium conductance. A residual barium-insensitive conductance was seen to reverse near -40 mV. Intracellular dialysis with guanosine 5'-o-(3-thiotriphosphate) significantly enhanced the duration of the TRH effect, indicating that G protein activation participates in the TRH response. These observations not only reveal a direct, G-protein-mediated depolarizing action of TRH on neonatal rat SPNs and lateral horn cells but also imply that two separate conductances may be involved in the TRH responses in some neurons.

1. Intracellular recording from medial gastrocnemius (MG) motoneurones was used to examine postsynaptic potentials produced by electrical stimulation of the plantaris nerve at group I strength at rest and during fictive locomotion. Fictive locomotion was evoked by stimulation of the midbrain locomotor region (MLR) in decerebrate cats or in decerebrate, acute low-spinal cats by perineal stimulation following intravenous administration of clonidine and naloxone. 2. In both MLR and spinal fictive locomotor preparations, stimulation of plantaris nerve group I afferents at rest evoked short-latency (< 2 ms) IPSPs in MG motoneurones. During the extensor phase of MLR-evoked locomotion, the same stimulation produced short-latency (1.6-1.8 ms) EPSPs. Such latencies suggest mediation by one interneurone interposed between plantaris nerve group I afferents and MG motoneurones. Non-monosynaptic, short-latency excitation was not seen at rest nor during the flexion phase of the step cycle. 3. Group I EPSPs during the extensor phase of MLR-evoked locomotion were evoked by stimulation at intensities ranging from 1.4-2 times threshold (T). The effectiveness of stimulation intensities < 1.5 T suggests that activation of group II afferents is not required to evoke disynaptic excitation. Selective activation of group Ia afferents by stretches of the Achilles tendon also produced disynaptic EPSPs during extension. 4. During fictive locomotion in spinal animals pretreated with clonidine, short-latency group I EPSPs were not seen but group I IPSPs recorded at rest disappeared or were greatly attenuated. The failure of depolarizing current to reveal group I IPSPs suggests that fictive locomotion involves an inhibition of the inhibitory interneurones that operate at rest. In both clonidine-treated spinal and MLR preparations, trains of stimuli at group I strength evoked longer-latency and slowly rising potentials that were more prominent during the flexor phase of fictive locomotion. 5. These results show a reduction in short-latency group I inhibition of synergists in both MLR and clonidine-treated spinal preparations during fictive locomotion. In addition, activation of group I afferents evokes short-latency excitation of synergists during extension in the MLR preparation. Such excitatory reflexes activated by ankle extensor group Ia and Ib afferents may form an excitatory feedback system, reinforcing on-going extensor activity during the stance phase of the step cycle.

Pudendal-to-pelvic and pudendal-to-pudendal reflexes are described in an in vitro brainstem-spinal cord neonatal rat preparation. Cystometrograms and peripheral pelvic nerve recordings were used to monitor excitatory micturition reflexes evoked by tactile perineal stimulation or by continuous electrical stimulation of the sensory pudendal nerve. Micturition was characterized by an increased bladder pressure and a period of tonic pelvic nerve activity during which time fluid was expelled from the urethra. Single stimuli delivered to the sensory pudendal nerve evoked a phasic response in the pelvic nerve (pudendal-to-pelvic reflex) or pudendal motor nerve (pudendal-to-pudendal reflexes). The pudendal-to-pelvic reflex consisted of a single response occurring after a mean latency of 98 +/- 24 ms. The pudendal-to-pudendal reflex was comprised of two responses, the first occurred at a mean latency of 105 +/- 11 ms and the second at 383 +/- 36 ms. Cervical or lower thoracic spinal transection did not alter the pudendal-to-pelvic reflex, however, the second component of the pudendal-to-pudendal reflex was abolished. The use of preganglionic pelvic and pudendal peripheral nerve recordings described in this study provide a direct measure of the reflex outflow from the CNS and can be used to examine developmental changes and neurochemical substrates within the CNS which contribute to micturition and coital reflexes in the rat.

1. This investigation examined primary afferent depolarization (PAD) of perineal afferents during micturition and evoked by electrical stimulation of perineal, hindlimb cutaneous and muscle-nerves. PAD was inferred from changes in excitability of spinal terminals of single afferents in decerebrate and chloralose-anaesthetized paralysed male cats. Observations were made on perineal afferent fibres travelling in the sensory branch of the pudendal (SPud) and superficial perineal (SPeri) nerves. 2. Micturition was evoked by distension of the bladder and excitability changes were measured in twenty-seven SPud afferents. In ten afferents, there was evidence of PAD during micturition. The time course of PAD was similar to the period of decreased activity in sphincter muscle efferents during micturition. In four afferents, there was decreased excitability during voiding that was interpreted as removal of tonic PAD. In the remaining thirteen afferents there were no detectable changes in excitability. Bladder distension in the absence of micturition failed to change the excitability of any SPud afferents tested. 3. Almost all SPud afferents were subject to PAD upon stimulation of cutaneous nerves. Superficial perineal, long saphenous, caudal cutaneous sural and the predominantly cutaneous posterior tibial nerves were particularly effective in evoking PAD. While group I strength stimulation of hindlimb muscle-nerves produced PAD of some SPud fibres, group II stimulation often increased the magnitude or incidence of PAD. The patterns and magnitude of PAD observed in SPeri afferents were similar to those observed in SPud afferents. 4. Since some SPud afferents were subject to PAD during micturition, PAD is probably one mechanism responsible for suppression of sphincter reflexes during micturition. Additional roles of PAD of perineal afferents evoked by activation of hindlimb cutaneous and muscle afferents are discussed.

The external urethral sphincter (EUS) and external anal sphincter (EAS) are striated muscles that function to maintain urinary and fecal continence respectively. This study examines the short-latency synaptic input from a variety of cutaneous perineal and muscle/cutaneous hindlimb afferents to the motoneurons innervating these muscles. Intracellular recordings from antidromically identified EUS and EAS motoneurons provided records of the postsynaptic potentials (PSPs) produced by electrical stimulation of peripheral afferents in decerebrate or chloralose anesthetized cats. Excitatory postsynaptic potentials (EPSPs) were produced in most EUS and EAS motoneurons by stimulation of ipsilateral and contralateral sensory pudendal (SPud) and superficial perineal (SPeri) cutaneous nerves. The shortest central latencies in the study (1.5 ms) suggest that there are disynaptic excitatory, in addition to tri- and oligosynaptic, connections within these reflex pathways. EPSPs mixed with longer latency inhibitory potentials (E/I PSPs) were observed in both motoneuron populations, but were found more frequently in EAS motoneurons. These E/I PSPs were evoked more often from contralateral afferents than from ipsilateral afferents. Cutaneous nerves innervating the hindlimb had weaker if any synaptic effects on sphincter motoneurons. Stimulation of ipsilateral hindlimb muscle nerves rarely produced PSPs in EUS motoneurons and had weak synaptic actions on EAS motoneurons. In 2 of 22 animals (both decerebrate), large inhibitory potentials predominated over early small EPSPs suggesting that inhibitory pathways from these afferents to sphincter motoneurons can be released under certain circumstances. The relation between the segmental afferents to EUS and EAS motoneurons and the neural circuitry influencing them during micturition and defecation are discussed.

Repetitive firing of motoneurones was examined in decerebrate, unanaesthetised, paralysed cats in which fictive locomotion was induced by stimulation of the mesencephalic locomotor region. Repetitive firing produced by sustained intracellular current injection was compared with repetitive firing observed during fictive locomotion in 17 motoneurones. During similar interspike intervals, the afterhyperpolarisations (AHPs) during fictive locomotion were decreased in amplitude compared to the AHPs following action potentials produced by sustained depolarising current injections. Action potentials were evoked in 10 motoneurones by the injection of short duration pulses of depolarising current throughout the step cycles. When compared to the AHPs evoked at rest, the AHPs during fictive locomotion were reduced in amplitude at similar membrane potentials. The post-spike trajectories were also compared in different phases of the step cycle. The AHPs following these spikes were reduced in amplitude particularly in the depolarised phases of the step cycles. The frequency-current (f-I) relations of 7 motoneurones were examined in the presence and absence of fictive locomotion. Primary ranges of firing were observed in all cells in the absence of fictive locomotion. In most cells (6/7), however, there was no relation between the amount of current injected and the frequency of repetitive firing during fictive locomotion. In one cell, there was a large increase in the slope of the f-I relation. It is suggested that this increase in slope resulted from a reduction in the AHP conductance; furthermore, the usual elimination of the relation is consistent with the suggestions that the repetitive firing in motoneurones during fictive locomotion is not produced by somatic depolarisation alone, and that motoneurones do not behave as simple input-output devices during this behaviour. The correlation of firing level with increasing firing frequency which has previously been demonstrated during repetitive firing produced by afferent stimulation or by somatic current injection is not present during fictive locomotion. This lends further support to the suggestion that motoneurone repetitive firing during fictive locomotion is not produced or regulated by somatic depolarisation. It is suggested that although motoneurones possess the intrinsic ability to fire repetitively in response to somatic depolarisation, the nervous system need not rely on this ability in order to produce repetitive firing during motor acts. This capability to modify or bypass specific motoneuronal properties may lend the nervous system a high degree of control over its motor output.

Electrical stimulation of sensory pudendal and superficial perineal nerves evokes focal synaptic potentials produced by activation of spinal neurons in the lumbosacral gray matter in chloralose anesthetized or decerebrate cats. The field potentials evoked by sensory pudendal nerve stimulation were located in medial parts of laminae V and VI, and lamina X in the S1 to S3 spinal segments. The superficial perineal cutaneous field potentials partially overlapped with those produced by the pudendal nerve, but in general were localized more laterally in laminae V and VI. The central latencies of the earliest portion of the field potentials evoked by either sensory pudendal or superficial perineal nerves were less than 0.9 ms suggesting that monosynaptic activation of neurons contributed to the potentials.

Membrane electrical properties of motoneurons innervating the striated muscle of the external urethral and anal sphincters were examined in the decerebrate cat. Both populations of motoneurons had similar electrical properties (mean pooled values; conduction velocity 48 m/s, membrane time constant 3.3 ms, afterhyperpolarization (AHP) duration 97 ms, membrane input resistance 2.2 M omega, rheobase 3.3 nA, and threshold voltage 8.1 mV). Although a portion of cells in both subpopulations of sphincter motoneurons displayed subthreshold conductances (i.e. sag, anomalous rectification), the incidence was higher in the external urethral sphincter motoneurons. The sphincter motoneuron membrane properties were likened to 'slow' hindlimb motoneurons and the low rheobase values suggest that the sphincter motoneurons are easily recruited.

Electrical stimulation of the spinal cord above the sacral segments was used to produce coordinated micturition in the paralysed decerebrate cat. Stimulation of the superficial aspect of the dorsolateral funiculus (DLF) within the lower thoracic (T9-T13) segments produced a bladder contraction coordinated with decreased activity in the external urethral sphincter (EUS) branch of the pudendal nerve during which time fluid was expelled. In addition, a similar response was observed with DLF stimulation at the boundary of the L5/L6 segments. At the second cervical spinal segment, however, stimulation of a more lateral and ventral portion of the superficial spinal white matter was the only effective site for producing micturition. The spinal cord-evoked response was comparable to the micturition evoked by electrical stimulation of the pontine micturition centre (PMC) within the brainstem. A bilateral lesion of the dorsal columns (DC) and the dorsolateral funiculi (DLF) at the lower thoracic levels abolished reflex micturition evoked by bladder distension. However stimulation rostral to the lesion, within the PMC or thoracic DLF, continued to produce coordinated bladder and sphincter response during voiding. Stimulation caudal to the lesion produced a decrease in pudendal nerve activity but did not produce a void or bladder pressure change. This reduction in pudendal nerve activity could be abolished with a second lesion of the superficial DLF caudal to the stimulation site. It was concluded that stimulation of the thoracic dorsolateral funiculus activates both ascending and descending fibres which can influence the bladder and/or sphincter muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

A compartmental neuronal model was used to show that increased compartmental leak conductances distal to the site of excitatory postsynaptic potential (EPSP) generation have little effect on EPSP amplitude but decrease half-width markedly. Using intracellular recording from cat hindlimb motoneurons, reductions of composite Ia EPSP amplitude by up to 70% unaccompanied by reductions in half-width were seen following conditioning stimuli to hindlimb nerves. Appropriate condition-test intervals produced large reductions in EPSP amplitude that were unaccompanied by detectable increases in motoneuron conductance. These observations suggest that presynaptic inhibition and not increased postsynaptic motoneuron conductances is responsible for large EPSP amplitude reductions following conditioning stimulation.

We tested the hypothesis that stimulation of the mesencephalic locomotor region (MLR) activates polysynaptic pathways that project to lumbar spinal motoneurons and are involved in the initiation of locomotion. Fictive locomotion was produced by MLR stimulation, and intracellular records of evoked postsynaptic potentials (PSPs) in alpha-motoneurons were computer analyzed. Stimulation of sites in the MLR that were maximally effective for the initiation of locomotion produced excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) in all the motoneurons examined. The amplitudes of the PSPs increased as locomotion commenced. The EPSPs were largest during the depolarized phase of the step cycle, and in 17 of our 22 cells the EPSP was replaced by an IPSP of slightly longer latency during the hyperpolarized phase. The mean latency of the EPSPs measured from the stimulus artifact produced by stimulation of the MLR was 5.1 ms (3.0-7.0 ms). In all cases, the IPSP occurred 0.6 ms or more after the onset of the EPSP in the same cell. Later PSPs were sometimes observed as well. The effects of constant current injection on the membrane potential oscillations associated with fictive locomotion (locomotor drive potentials) were examined. The results showed that the amplitudes of the locomotor drive potentials (LDPs) could be affected by depolarizing and hyperpolarizing current injection. The data is consistent with the LDP having a predominant inhibitory component, which is more readily altered by current injection than is the excitatory component. The effect of constant current injections on the MLR-evoked PSPs was also examined, and it was observed that both EPSPs and IPSPs could be affected by the injected currents. The EPSPs increased in amplitude with constant hyperpolarizing current injection, and this fact rules out the possibility that the EPSP is actually a reversed IPSP. The IPSP was decreased in amplitude by hyperpolarizing current injection. Combined stimulation of the MLR and the ipsilateral high-threshold muscle or cutaneous afferents produced facilitation of both short- and long-latency MLR-evoked PSPs, suggesting that the two pathways share common interneurons. The possibility that the long-latency PSPs are produced by rapid oscillation in the locomotor central pattern generator is discussed. We concluded that MLR stimulation that evokes fictive locomotion produces both excitation and inhibition of spinal motoneurons. Spinal interneuronal systems are implicated and may be those involved in the initiation and control of locomotion. The probable relay sites for the descending pathway from the MLR to motoneurons are discussed.

The evidence suggests that the mesencephalic locomotor region (MLR) may not be a unitary region since anatomical and functional variations in the descending projections are clearly indicated. Reversible cooling of midline reticular structures can effectively block locomotion evoked by stimulation of lateral MLR (L3.5-4) sites while not significantly affecting the locomotion evoked from more medial MLR (L2-2.5) sites. In contrast, locomotion evoked by stimulation of the medial MLR sites is blocked by cooling of the ipsilateral lateral brainstem region which corresponds to the pontomedullary strip (PLS). Ipsilateral PLS cooling was not effective for blocking lateral MLR evoked locomotion, and contralateral PLS cooling was not effective for blocking either medial or lateral MLR evoked stepping. The evidence indicates that the lateral MLR relays through medial reticular nuclei while the medial MLR sites relay largely through the lateral brainstem structures often referred to as the PLS.

Modulation of synaptic potentials produced by electrical stimulation of low-threshold muscle afferents in lumbar alpha-motoneurons innervating knee and ankle muscles was studied by intracellular recording during "fictive locomotion" induced by stimulating the mesencephalic locomotor region (MLR) in paralyzed, mesencephalic cats. Averaging postsynaptic potentials in different phases of the fictive step cycle indicated that relatively little amplitude modulation occurred. In nearly half of the 38 motoneurons analyzed, there was a statistically significant tendency for excitatory postsynaptic potentials (EPSPs) to increase in amplitude during the depolarized phase of the oscillation in the membrane potential produced during fictive locomotion (locomotor-drive potential). In 8% the EPSPs decreased under the same conditions, while the rest displayed a constant amplitude during all phases of the fictive step cycle. Only three cells showed a distinct second peak in the EPSP at a latency consistent with transmission in a di- or trisynaptic pathway. Late inhibitory postsynaptic potentials (IPSPs) were also rarely observed. Thus oligosynaptic pathways from muscle afferents to the motoneuron groups studied are not prominent during the locomotor cycle in this preparation. We suggest that the marked modulation of monosynaptic reflex amplitude observed in mesencephalic cats (1) arises mainly from the effects of the locomotor-drive potential in bringing the cells closer to threshold during some phases of locomotion. Specific modulation during fictive locomotion of transmission in pathways from muscle afferents, which has been demonstrated for cutaneous pathways (28), was not observed. The implications of these results for the control of locomotion are discussed briefly.

The ability of electrical stimulation of the pontine micturition centre (PMC) to produce voiding following lumbosacral deafferentation was examined. Transection of the S3 to L7 dorsal resulted in the abolition of distension-evoked micturition while electrical stimulation of the PMC continued to produce micturition. Removal of the L7 to S2 dorsal root ganglia did not alter the PMC-evoked response, nor did transection of the dorsal roots in more rostral lumbar and thoracic segments. It appears that the PMC can activate a central neural network and produce micturition independently of lumbosacral reflex pathways.

The contribution of Renshaw cell (RC) activity to the production of fictive locomotion in the mesencephalic preparation was examined using the nicotinic antagonist mecamylamine (MEC). After the i.v. administration of 3 doses of MEC (1.0 mg/kg) the following observations were made: 1) ventral root (VR) evoked discharge of RCs was decreased by up to 87.7%, 2) recurrent inhibitory postsynaptic potentials recorded in alpha motoneurons were greatly reduced or abolished, and 3) the rhythmic firing of RCs during the fictive step cycle was abolished in 83% of the cells examined. Locomotor drive potentials (LDPs) in motoneurons persisted during the fictive step cycle after MEC administration. Bursts of motoneuron firing during each fictive step cycle were characterized by increased frequency and number of spikes after MEC, although the burst duration was unaltered for similar step cycle lengths. A greater number and frequency of spikes per burst was also observed in Ia inhibitory interneurons (IaINs), which remained rhythmically active after MEC administration. It is concluded that Renshaw cells are not an integral part of the spinal central pattern generator for locomotion, nor do they control the timing of the motoneuron or IaIN bursts of firing during fictive locomotion. The data are consistent with a role for RCs in limiting the firing rates of motoneurons and IaINs during each burst.

Input-resistance changes during fictive locomotion were monitored in a variety of extensor and flexor hindlimb alpha-motoneurons in precollicular, postmammillary decerebrate cats induced to "walk" by electrical stimulation of the mesencephalic locomotor region (MLR). Using intracellular recording techniques and injected hyperpolarizing current pulses, the changes in the motoneuron input resistance recorded at the motoneuron soma were examined during nonlocomoting control periods as well as during the depolarized and hyperpolarized phases of the membrane potential oscillations (locomotor drive potentials, or LDPs) of fictive locomotion. In 28 of the 52 motoneurons examined, no change in the input resistance between the control and locomotor periods was observed. The remainder of the cells displayed a decrease (less than 20%) in input resistance when fictive stepping commenced. Over 80% of all the motoneurons depolarized (mean depolarization 4 mV), whereas only one LG motoneuron hyperpolarized (2 mV) with the onset of stimulation of the MLR. The remaining motoneurons did not display such changes. In 43 out of 52 motoneurons examined, no significant change in the input resistance could be observed between the depolarized and hyperpolarized phases of the step cycle. A decrease in the input resistance during the depolarized phase of the LDP was observed in four LG motoneurons, whereas five other motoneurons (2 LG, 1 TA, 1 PB, and 1 ST) displayed an increased input resistance during the depolarized phase compared with the hyperpolarized phase of locomotion. The data are consistent with the presence of an excitatory synaptic input alternating with an inhibitory input to the motoneuron during the fictive step cycle.(ABSTRACT TRUNCATED AT 250 WORDS)