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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.

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.

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.

These experiments were undertaken to examine whether both premotoneuronal mechanisms and direct actions on motoneurons could contribute to suppression of excitatory perineal reflex pathways during micturition. Intracellular recordings were obtained from motoneurons innervating the external urethral sphincter (EUS), external anal sphincter (EAS), and selected hindlimb muscles in decerebrate male cats. The peak amplitudes of EPSPs evoked by electrical stimulation of peripheral cutaneous afferents were measured during micturition. In the EUS, EAS, and hindlimb motoneurons examined, EPSPs produced by stimulation of perineal afferents (superficial perineal or sensory pudendal nerves) were reduced in amplitude during micturition. The sample of PSPs evoked by stimulation of hindlimb cutaneous nerves recorded in hindlimb motoneurons revealed that these PSPs could also be reduced. In contrast, no changes were seen in monosynaptic EPSPs evoked by muscle afferent stimulation. The present study demonstrates that during micturition there is a strong suppression of perineal reflexes to both sphincter and hindlimb motoneurons. Since reduced EUS activity is required for efficient micturition, suppression of the strong excitatory perineal input to EUS motoneurons likely contributes to decreased EUS activity during the bladder contraction. It appears that the micturition circuitry utilizes both premotoneuronal mechanisms and direct motoneuronal inhibition to achieve this reflex suppression. The function of the micturition-related reduction of perineal reflexes to hindlimb or EAS motoneurons is not known at this time and further investigations are required to elucidate the interaction between micturition circuitry and hindlimb cutaneous pathways.

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.

Intracellular recordings from external urethral sphincter (EUS) and external anal sphincter (EAS) motoneurons were obtained during micturition in the decerebrate cat. The neural circuitry mediating micturition was activated by distension of the bladder or by electrical stimulation of the pontine micturition center (PMC). During micturition, the membrane potential of EUS motoneurons hyperpolarized 3-9 mV, during which time the motoneuron somatic membrane conductance increased. The membrane hyperpolarization could be reversed with passive diffusion or active ejection of chloride from the intracellular microelectrode into the motoneuron. In contrast, the membrane potential of EAS motoneurons either depolarized slightly or showed no change during micturition. We have shown that the neural circuitry mediating micturition can influence the EUS and EAS independently. In addition, stimulation of the PMC provides a valuable tool for identifying spinal neurons mediating the postsynaptic inhibition of EUS motoneurons during micturition.

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.