Excitatory and inhibitory influences on bladder activity elicited by electrical stimulation in the pontine micturition center in the rat

Electrical stimulation at various sites in the dorsal pontine tegmentum in urethane anesthetized rats modulated activity of the urinary bladder as well as efferent firing on bladder postganglionic nerves. Electrical stimulation (0.2 ms 50 Hz, 5-20 V or 30-150 microA, 2-5 s train duration) using a microelectrode (tip diameter, 10-20 microns) in an excitatory area located rostral and medial to the locus coeruleus evoked short latency (less than 2 s) large amplitude (greater than 20 cm H2O) bladder contractions and increased firing on the bladder postganglionic nerves. Stimulation at sites adjacent to the excitatory area inhibited bladder postganglionic nerve firing and bladder activity. Inhibitory responses were evident as either a decrease in intravesical pressure, an increased interval between bladder contractions, or an interruption or elimination of bladder contractions. The threshold intensity for excitation using a large electrode (2-4 V) was slightly higher than that for inhibition (1.5-2 V). The optimum sites for evoking bladder contractions were located in and close to the laterodorsal tegmental nucleus (LDT) and in the periaqueductal gray just dorsal or dorsolateral to the LDT. The extent of the area that induced bladder contractions was 0.5-1.2 mm in diameter in each rat when a microelectrode was employed for electrical stimulation. Electrical stimulation in the optimum site for evoking bladder contractions induced relatively little striated muscle activity and produced no short-latency blood pressure changes. The longer latency blood pressure changes associated with a spontaneous bladder contraction were still present following a stimulation of the dorsolateral pons. These data are consistent with the view that neurons in the dorsal pontine tegmentum play an important role in the regulation of urine storage as well as urine release.     

Pontine control of the urinary bladder and external urethral sphincter in the rat

Neurons in the rostral pontine tegmentum are known to have an important role in controlling micturition. The present experiments used urethane anesthetized rats to examine the effects of electrical stimulation at various sites in the pons on bladder and external urethral sphincter activity and on the volume threshold for inducing micturition. Stimulation with short trains of pulses (50 Hz, 1-3 s trains, 1-15 V) in the laterodorsal tegmental nucleus (LDT), the periaqueductal grey (PAG) or the lateral parabrachial nucleus (L-PBN) elicited contractions of a partially filled, quiescent bladder. However stimulation during a bladder contraction aborted the contraction indicating that these areas have inhibitory as well as excitatory effects. Continuous stimulation (50 Hz) in the PAG or L-PBN during a cystometrogram decreased bladder capacity (mean decrease 36%). Conversely, continuous stimulation in the pontine reticular formation (in or near the dorsal subcoeruleus nucleus and medial parabrachial nucleus) increased bladder capacity (mean increase 50%). Stimulation at pontine sites (LDT, PAG and L-PBN) which elicited bladder contractions also elicited an increase in external urethral sphincter activity. A similar increase in urethral sphincter activity occurred during reflex micturition induced by bladder distension. These data suggest that bladder capacity and the coordination of bladder and external urethral functions are controlled by various neuronal populations in the rostral pons of the rat.     

Transmission of afferent information from urinary bladder, urethra and perineum to periaqueductal gray of cat

The micturition reflex pathway is a supraspinal pathway. Anatomical tracing evidence is compatible with an involvement of the periaqueductal gray (PAG) in the ascending limb of this reflex. We tested the involvement of the PAG in receiving urinary tract- or perineum-related information and attempted to characterize this ascending path in terms of what type of information is being conveyed. Electrical stimulation of the pelvic nerves, which carry afferent information from the urinary bladder, evoked maximum field potentials in the caudal third of the PAG, primarily in the dorsal part of the lateral PAG and in the ventrolateral PAG. Since the regions activated by pelvic nerve stimulation differed from those activated by stimulation of the sensory pudendal or superficial perineal nerves, it is possible that specific pathways for different nerve inputs to the PAG exist. Sacral spinal cord neurons ascending to the PAG were identified by antidromic activation and then tested for inputs from pelvic, sensory pudendal or superficial perineal nerves. Of 18 units identified, only five received inputs from any of the peripheral nerves tested and only two projecting neurons received a pelvic nerve input. Thus the PAG may receive inputs from bladder and perineum, but the small proportion of cells with direct projections to the PAG receiving inputs from our test nerves implies that the major part of this pathway is not directly related to lower urinary tract function.     

Properties of the descending limb of the spinobulbospinal micturition reflex pathway in the cat

The micturition reflex is thought to be mediated by a spinobulbospinal reflex pathway passing through the rostral pons. This study examined the properties of the descending limb of the reflex pathway by monitoring the responses of the lower urinary tract to stimulation of the pons in the decerebrate cat. Electrical stimulation (300 μs pulses at 50 Hz intratrain frequencies, 300–500 ms trains, 0.5–15 V) in the region of the locus coeruleus (P 0.5–3.1/L 2–4/H to −2.75) was used to activate the descending excitatory pathway to the sacral parasympathetic nucleus. Low intensity stimulation induced small amplitude, short duration (14 ± 11cm H₂O, 10 ± 3s) bladder contractions in a partially full bladder, whereas higher intensity stimulation induced large amplitude, long duration (69 ± 29cm H₂O, 70 ± 44s) contractions which were similar to distension-induced reflex micturition contractions. The evoked bladder contractions coincided with a reduction in external urethral sphincter (EUS) EMG activity. Following bilateral L₇-S₃ dorsal root transection, electrical stimulation of the pons still elicited the small amplitude bladder contractions, but the larger amplitude, long duration micturition contractions were abolished. During these small evoked bladder contractions, a suppression of EUS activity still occurred following deafferentation, indicating a pontine mediated bladder/EUS synergy. It is concluded that the pons can initiate bladder contractions and coordinated bladder-sphincter activity, but that afferent feedback (via the dorsal roots) is needed to maintain the large amplitude micturition contractions.     

Pudendal-to-bladder reflex in chronic spinal-cord-injured cats

The effects of pudendal nerve stimulation on reflex bladder activity were investigated in cats with chronic spinal cord injury (6-12 months) under alpha-chloralose anesthesia. Electrical stimulation of the pudendal nerve on one side at different frequencies and intensities induced either inhibitory or excitatory effects on bladder activity. The inhibitory effect peaked at a stimulation frequency of 3 Hz and gradually decreased at lower or higher frequencies. The inhibitory effect could occur at stimulation intensities between 0.3 and 1 V (pulse width 0.1 ms) and increased at intensities up to 10 V. Stimulation of the central end of transected pudendal nerve also inhibited bladder activity, indicating that afferent axons in pudendal nerve are involved. Nerve transections also showed that both hypogastric and pelvic nerves might be involved in the inhibitory pudendal-to-bladder spinal reflex. Pudendal nerve stimulation at 20 Hz and at the same intensities (1-10 V) elicited a bladder excitatory response. Although this excitatory effect could not sustain a long lasting bladder contraction at small bladder volumes, it did induce continuous rhythmic bladder contractions at large bladder volumes. This study indicated the possibility of developing a neuroprosthetic device based on pudendal nerve electrical stimulation to restore micturition function after spinal cord injury.     

Somato-vesical reflexes in chronic spinal cats

The effects of afferent volleys in hindlimb cutaneous and muscle nerves on vesical tone and contractility and on the discharges in pelvic nerves to the bladder were measured in anesthetized CNS-intact and 2-19 months chronic spinal cats. In chronic spinal cats volleys in group III and IV fibers increased the tone of the quiet, empty bladder (excitatory somato-vesical reflex). The same volleys inhibited the slow, large, rhythmic micturition contractions of the expanded bladder (inhibitory somato-vesical reflex). In CNS intact cats single or short tetanic volleys induced a reflex discharge in pelvic vesical nerve branches with 3 distinct components. These reflexes could be observed during micturition contractions, not markedly between the contractions or when the bladder was empty and quiet. The latencies of the 3 components were 90, 320 and 770 ms, respectively. The two early components (AI- and A2-reflex) were evoked by volleys in group II and III hindlimb afferents. The late component (C-reflex) was induced by group IV volleys. In chronic spinal cats a group II and III-induced A-reflex (latency 90 ms) and a group IV-induced C-reflex (latency 340 ms) were observed. The central pathways and the physiological significance of the various somato-vesical reflexes are discussed.     

Neural organization of the viscero-cardiac reflexes

The reflex responses evoked in the postganglionic nerves to the heart were tested in chloralose-anaesthetized cats. Electrical stimulation of the A delta afferent fibres from the left inferior cardiac nerve evoked spinal and supraspinal reflex responses with the onset latencies of 36 ms and 77 ms respectively. The most effective stimulus was a train of 3-4 electrical pulses with the intratrain frequency of 200-300 Hz. Electrical stimulation of the high threshold afferent fibres (C-fibres) from the left inferior cardiac nerve evoked the reflex response with the onset latency of 200 ms. The C-reflex was present in intact animals and disappeared after spinalization. The most effective stimulus to evoke this reflex was a train of electrical pulses delivered at a frequency of 1-2 Hz with an intratrain frequency of 20-30 Hz. The most prominent property of the C-reflex was its marked increase after prolonged repeated electrical stimulation. We conclude that: (1) viscero-cardiac sympathetic reflexes may be organized at the spinal and supraspinal level; (2) viscero-cardiac sympathetic reflexes evoked by stimulation of the A delta and C afferent fibres from the left inferior cardiac nerve have different central organization.     

A sympathetic projection from sacral paravertebral ganglia to the pelvic nerve and to postganglionic nerves on the surface of the urinary bladder and large intestine of the cat

Anatomical and electrophysiological experiments have demonstrated a prominent projection from the sacral sympathetic chain via the pelvic nerve to postganglionic nerves on the surface of the urinary bladder and the large intestine of the cat. Retrograde labeling studies revealed that the pelvic nerve, which is generally believed to carry primarily parasympathetic axons, has a considerable population of sympathetic fibers originating mainly from the S1-S3 paravertebral ganglia. The number of sympathetic neurons projecting to the pelvic nerve (2,100) was about 75% of that projecting to the pudendal nerve (2,900), a somatic nerve which would be expected to carry a large sympathetic fiber constituent. Sympathetic neurons projecting to the pudendal nerve were located primarily in the L6-S2 ganglia. Electrophysiological studies confirmed the presence of a sympathetic pathway from the paravertebral ganglia to the pelvic viscera. Electrical stimulation (thresholds 1.5-3 V) of the lumbar sympathetic chain evoked firing in the pelvic nerve and in postganglionic nerves on the surface of the colon and bladder at latencies of 60-150 msec. The responses were unaffected by cutting the chain one segment rostral to the site of stimulation, but were abolished by the administration of a ganglionic-blocking agent (tetraethylammonium). The responses on the colon and bladder postganglionic nerves were also abolished by transection of the pelvic nerve. The conduction velocity in the sympathetic postganglionic axons was approximately 1 m/second. In summary, these studies indicate that the pelvic nerve, like somatic nerves, receives a prominent projection from the sympathetic chain ganglia. The function of this sympathetic paravertebral pathway and its relationship with prevertebral innervation of the pelvic organs remains to be established.     

Pharmacological modulation of the pontine micturition center.

Previous studies have indicated that an area of the rostral pontine tegmentum known as the 'pontine micturition center' (PMC) plays an essential role in the regulation of lower urinary tract function. The present pharmacologic experiments were conducted on either decerebrate unanesthetized or chloralose anesthetized cats to identify the location of the PMC and to examine the neurotransmitter mechanisms controlling micturition. Microinjections of excitatory and inhibitory amino acids were made at stereotaxic coordinates P1 to P3, L2 to L3, H0 to H-4 where electrical stimulation with trains of pulses (2-30 V, 80-120 Hz and 50-300 ms train duration) elicited short latency (less than 2 s) bladder contractions or voiding. Injections of L-glutamate (L-GLUT) (20-130 nmol) or DL-homocysteic acid (DLH) (20-100 nmol) into the region of the locus coeruleus or parabrachial nucleus elicited voiding as well as an increase in the frequency or amplitude of isovolumetric bladder contractions. In some anesthetized animals, L-GLUT and DLH also had mixed excitatory-inhibitory or pure inhibitory effects. Injections of muscimol (9-70 nmol) depressed rhythmic bladder activity, increased the bladder volume for inducing micturition or completely abolished the voiding induced by bladder filling. The inhibitory effects of muscimol were reversed by microinjections of bicuculline methiodide (BCMI) (3-22 nmol). Injections of BCMI (1-1.5 nmol) into untreated cats stimulated bladder activity and lowered the bladder volume for inducing micturition. It is concluded that: (1) neurons in the rostral pons are an essential component of the micturition reflex pathway, (2) several populations of neurons located in the region of the locus coeruleus complex and parabrachial nucleus contribute to the functions of the PMC, and (3) PMC neurons are under a tonic GABAergic inhibitory control which regulates the micturition threshold and in turn regulates bladder capacity.     

Bladder emptying by intermittent electrical stimulation of the pudendal nerve

Persons with a suprasacral spinal cord injury cannot empty their bladder voluntarily. Bladder emptying can be restored by intermittent electrical stimulation of the sacral nerve roots (SR) to cause bladder contraction. However, this therapy requires sensory nerve transection to prevent dyssynergic contraction of the external urethral sphincter (EUS). Stimulation of the compound pudendal nerve trunk (PN) activates spinal micturition circuitry, leading to a reflex bladder contraction without a reflex EUS contraction. The present study determined if PN stimulation could produce bladder emptying without nerve transection in cats anesthetized with alpha-chloralose. With all nerves intact, intermittent PN stimulation emptied the bladder (64 +/- 14% of initial volume, n = 37 across six cats) more effectively than either distention-evoked micturition (40 +/- 19%, p < 0.001, n = 27 across six cats) or bilateral intermittent SR stimulation (25 +/- 23%, p < 0.005, n = 4 across two cats). After bilateral transection of the nerves innervating the urethral sphincter, intermittent SR stimulation voided 79 +/- 17% (n = 12 across three cats), comparable to clinical results obtained with SR stimulation. Voiding via intermittent PN stimulation did not increase after neurotomy (p > 0.10), indicating that PN stimulation was not limited by bladder-sphincter dyssynergia. Intermittent PN stimulation holds promise for restoring bladder emptying following spinal injury without requiring nerve transection.     

Cystometric changes in alloxan diabetic rats: evidence for functional and structural correlates of diabetic autonomic neuropathy

Autonomic neuropathy and urinary bladder function were compared in Sprague-Dawley rats with alloxan-diabetes of 3 months duration, rats fed sucrose for 8 weeks, and rats examined 8 weeks after pelvic nerve surgical axotomy; normal age-matched rats were used as controls. All experimental interventions induced bladder hypertrophy with increased bladder weight. In diabetic and sucrose-fed animals, water intake and urinary output increased. Cystometric recordings of normal rats in vivo showed rhythmic contractions (1.25 +/- 0.25 contr/min) with threshold volume for micturition reflex at 0.51 +/- 0.04 ml. In diabetic rats, bladder contractions were irregular and of lower frequency (0.60 +/- 0.04 contr/min), while threshold volume was significantly higher (1.00 +/- 0.11 ml). Bladder contractions were normal in sucrose-fed animals, though threshold volume was markedly augmented (1.27 +/- 0.19 ml). Pelvic nerve surgical ablation abolished micturition reflex. In bladder strips excised post-mortem, contractile response to field stimulation was reduced in diabetic rats compared to control and sucrose-fed animals. Morphological examination of pelvic and hypogastric nerves revealed abnormalities characteristic of diabetic neuropathy only in diabetic rats. These data suggest that in alloxan-induced diabetes the decrease in the rate of bladder contraction is the result of autonomic neuropathy; while bladder hypertrophy in sucrose-fed rats appears to be an organ adaptation to hyperdiuresis.     

Restoration of micturition using microelectric current in experimentally induced spastic urinary bladder in rabbits

The 29 rabbits used in this study were divided into three groups, A (A1 and A2), B, and C. In subgroup A1, 4 animals were used in order to verify whether the contact of an electrode to the sacral nerves results in some abnormality of voiding reflex. In subgroups A1 and A2 (4 animals each) we further studied the micturition function using three parameters: (i) urinary bladder fluoroscopy and radiography, (ii) cystomanometry, and (iii) electromyography of the pelvic floor muscles (external sphinter). In group B (9 rabbits) spastic paraplegia and micturition disturbances resulted from spinal cord compression that was induced by inserting a balloon catheter into the T11-T12 intervertebral foramen. In this group the parameters studied revealed a spastic urinary bladder in all animals. Finally, the 12 animals of group C were rendered paraplegic as described in group B, and microelectrodes were placed over the sacral nerves as in subgroup A1. By applying a specific sequence of sacral nerve stimulation we succeeded in satisfactory urinary bladder emptying as confirmed by the micturition parameters studied: The urinary bladder pressure decreased from 65 +/- 3 to 28 +/- 3 mm Hg. The pelvic floor muscle amplitude was lowered from 130 +/- 7 to 20 +/- 3 microV, and finally the radiological bladder size also decreased from 38 cm2 before voiding to 18 +/- 3 cm2 after voiding. These results indicate that microelectric current stimulation of the sacral nerves, when applied under a specific sequence, could rather satisfactorily restore micturition disturbances, at least in this experimental animal.     

Anatomical and physiological observations on supraspinal control of bladder and urethral sphincter muscles in the cat

In 15 cats injections of 3H-leucine were made in the pontine tegmentum. Injections in the medial part of the dorsolateral pontine tegmentum (M-region) resulted in specific projections to the sacral intermediomedial and intermediolateral cell groups. The intermediolateral cell group contains preganglionic parasympathetic neurons that form the motor supply of the detrusor muscle of the bladder. Injections in the lateral part of the pontine tegmental field (L-region) produced labeled fibers in the nucleus of Onuf, which contains motoneurons innervating the pelvic floor including the anal and urethral sphincters. L-region projections to the sacral preganglionic parasympathetic neurons and M-region projections to the nucleus of Onuf were very limited or absent. In 12 cats physiological experiments were performed. Electrical stimulation in the L-region elicited a prompt increase in the pelvic floor EMG and urethral pressure but had little influence on the intravesical pressure. Stimulation in the M-region elicited a prompt decrease in the pelvic floor EMG and urethral pressure followed, after a delay of 2 seconds, by an increase in the intravesical pressure, so simulating normal micturition.     

Brain stem influences on the parasympathetic supply to the urinary bladder of the cat

(1)The brain stem of anaesthetized cats has been mapped between Horsley-Clark planes APO and P8.5 with electrical stimuli of low intensity in order to determine the areas which can produce excitatory of inhibitory influences on the spontaneously contracting, sympathetically denervated, urinary bladder. (2) Two inhibitory areas were found. The first extended from P3.0 to P8.5 and at all levels was coincident with the midline raphe nuclei. The second area occurred largely 2-3 mm lateral to the midline, in the area of the nucleus reticularis pontis caudalis rostrally, and the nuclei reticularis gigantocellularis and parvocellularis caudally. Both of these areas were found to inhibit bladder contractions with threshold stimulus parameters of 20-60 microamperemeter, 400 microseconds, 20 Hz. (3)One excitatory area was found, largely 3-4 mm lateral to the midline. This area appeared large and diffuse in the lateral reticular formation. It is possible that it originated in the pontine micturition centre in the rostral pontine tegmentum. Caudally, it shifted to occupy a ventrolateral position. This excitatory area was in close approximation to, and was probably interspersed with, the lateral inhibitory area. (4) In decerebrate preparations the areas that produced excitation or inhibition had the same distribution as those found in anaesthetized animals. (5) Single shock stimulation (100 microamperemeter, 400 microseconds, 0.5 Hz repetition frequency in the excitatory area could produce firing in pelvic nerve efferents to the bladder at latencies of 60-110 ms. The amplitude of such responses was dependent on the level of intravesical pressure. (6) Stimulation of the inhibitory areas produced no evoked responses in the pelvic nerve efferents, but could inhibit reflexly evoked responses in this nerve. The similarity in the time courses of the inhibitory effects from the two areas raises the possibility that one acts via the other.     

Stimulation of three areas of the primary motor cortex interrupts micturition in dogs.

To clarify the area of the motor cortex (M1) in dogs, which corresponds to the cortical area participating in voluntary interruption of micturition in humans, the cortical portions related to the external urethral sphincter were first clarified by recording of somato-sensory evoked potentials, and then systematic cortical stimulation was performed in anesthetized and paralyzed dogs. The hypogastric, pelvic and pudendal nerves innervating the lower urinary tract and rectum were severed to eliminate the secondary reflexes. Five foci were recognized in the cortical potentials evoked after stimulation of the pudendal nerve. These foci existed in the sacral (Sacral-S) and hind leg (Leg-S) areas of the somato-sensory cortex (S1), and in the sacral (Sacral-M), hind leg (Leg-M) and trunk (Abd-M) areas of the M1. Stimulation of the three M1 foci, but not the two S1 foci, provoked centrifugal firings of the pudendal urethral branch. The firings disappeared after cutting of the ipsilateral bulbar pyramis. When the M1 foci were stimulated during the micturition reflex, the reflex discharge of a pelvic vesical branch was interrupted concomitantly with firings of the urethral branch. The interruption was still induced after the pyramidotomy. Pulse train stimulation of these M1 foci reset the cycles (about 2 Hz) in the alternative rhythmic firings of the urethral and vesical branches, which are known to be formed in the pontine micturition center [31,32]. These results suggest that the pyramidal cells in the three M1 foci inhibit the pontine micturition center and concomitantly contract the external urethral sphincter through the pyramidal tract. The possible roles of these M1 foci were discussed.     

Ultrastructural evidence for a paucity of projections from the lumbosacral cord to the pontine micturition center or M-region in the cat: A new concept for the organization of the micturition reflex with the periaqueductal gray as central relay

Information concerning the rate of bladder filling is determined by receptors in the bladder wall and conveyed via afferent fibers in the pelvic nerve to sensory neurons in the lumbosacral cord. It was assumed that this information is relayed from the lumbosacral cord to a medial cell group in the dorsolateral pontine tegmentum, called the M-region, the pontine micturition center, or Barrington's nucleus. The M-region, in turn, projects via long descending pathways to the sacral parasympathetic motoneurons. In the present electron microscopic study, it was investigated in cats whether monosynaptic projections from lumbosacral neurons to the M-region indeed exist. Wheat-germ agglutinin-horseradish peroxidase injections were made into the lumbosacral cord. Many retrogradely labeled dendrites and somata were found in the M-region, but no labeled terminals were found on retrogradely labeled dendrites or somata. Only a small number of anterogradely labeled terminals, which were filled with mainly round vesicles, contacted unlabeled dendrites in the M-region. In contrast, many more anterogradely labeled terminals, which were filled with mainly round and, to a limited extent, dense core vesicles and with asymmetrical synapses, were found on dendrites in the lateral part of the periaqueductal gray (PAG). Previously (Blok and Holstege [1994] Neurosci. Lett. 166:93–96), it was demonstrated that the lateral part of the PAG contains neurons projecting to the M-region. A concept for the central organization of the micturition reflex is presented in which ascending projections from the lumbosacral cord convey information on bladder filling to the PAG. When the bladder contains so much urine that voiding is necessary, the PAG, in turn, triggers the M-region. The M-region, however, also receives afferents from the preoptic area, which might be involved in phe final decision to start micturition. © 1995 Wiley-Liss, Inc.     

Gastric vagal-splanchnic interactions in the brainstem of the cat

Brainstem unitary responses to gastric vagal-splanchnic nerve interactions were evaluated in anesthetized cats during electrical stimulation of the nerves. The gastric branches of the dorsal and ventral vagal trunks which serve the proximal stomach were electrically stimulated while recording in nucleus solitarius in the brainstem to identify evoked unitary responses. The vagally evoked brainstem responses were orthodromic in nature as evidenced by a slight variability in latency, reduction in the number of spikes upon decreasing stimulus strength and failure to follow higher stimulus frequencies. Interactions between gastric vagal input from the proximal stomach and left greater splanchnic nerve were evaluated by simultaneously stimulating the nerves electrically. Forty-three (16%) of the 265 gastric vagally evoked brainstem responses recorded were inhibited by simultaneously activating the left greater splanchnic nerve. The gastric vagally evoked responses inhibited by splanchnic input were nearly equally divided between the dorsal and ventral vagal trunks. Eighty-eight percent of those vagally evoked brainstem units inhibited by splanchnic input showed complete inhibition suggesting secure synaptic coupling. In addition, 3 gastric vagally activated brainstem units were identified which were also activated by greater splanchnic input. The latency of the splanchnic evoked brainstem response in these 3 units ranged from 55 to 89 ms compared to a mean latency of 290 ms (S.D. +/- 50 ms) for the vagally evoked brainstem response. Splanchnic electrical stimulation usually produced an inhibitory effect upon the vagally evoked brainstem response which persisted for approximately 30 s following termination of splanchnic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Micturition and the soul

There is a close connection between micturition and emotion. Several species use micturition to signal important messages as territorial demarcation and sexual attraction. For this reason, micturition is coordinated not in the spinal cord but in the brainstem, where it is closely connected with the limbic system. In cat, bladder afferents terminate in a cell group in the lateral dorsal horn and lateral part of the intermediate zone. Neurons in this cell group project to supraspinal levels, not to the thalamus but to the central periaqueductal gray (PAG). Neurons in the lateral PAG, not receiving direct sacral cord afferents, project to the pontine micturition center (PMC). The PMC projects directly to the parasympathetic bladder motoneurons and to sacral GABA-ergic and glycinergic premotor interneurons that inhibit motoneurons in Onuf's nucleus innervating the external striated bladder sphincter. Thus, PMC stimulation causes bladder contraction and bladder sphincter relaxation, i.e., complete micturition. Other than the PAG, only the preoptic area and a cell group in the caudal hypothalamus project directly to the PMC. The ventromedial upper medullary tegmentum also sends projections to the PMC, but they are diffuse and also involve structures that adjoin the PMC. Neuroimaging studies in humans suggest that the systems controlling micturition in cat and human are very similar. It seems that the many structures in the brain that are known to influence micturition use the PAG as relay to the PMC. This basic organization has to be kept in mind in the fight against overactive bladder (OAB) and urge-incontinence.     

Intracellular responses of raphe magnus neurons during the jaw-opening reflex evoked by tooth pulp stimulation

Neurons in the nucleus raphe magnus (RM) may play an important role in the modulation of nociception. To determine how RM neurons are activated during a nociceptive reflex, the intracellular responses of raphe neurons were studied during the jaw-opening reflex (JOR) elicited by tooth pulp shock in lightly anesthetized cats. Tooth pulp stimulation produces reflex EMG activation of the digastric muscle at a latency of 7-11 ms, resulting in jaw opening. Tooth pulp shock that elicits the JOR also produces an EPSP in a subset of raphe neurons. This EPSP consists of an early small depolarization that occurs at a latency of 10-15 ms followed by a larger depolarization at a latency of 20-60 ms. In all cases the latency to EPSP is longer than the latency to digastric EMG onset. Electrical stimulation of the 4 paws elicits oligosynaptic EPSPs in the same cells at a latency of 16-20 ms. Electrical train stimulation of the midbrain periaqueductal gray region (PAG) suppresses the JOR. Single shock stimulation at the same PAG sites that suppress the JOR evokes monosynaptic EPSPs in the large majority of raphe neurons recorded. In all cases, the threshold for EPSP is below the threshold for suppression of the JOR. The EPSP amplitude is a direct function of PAG stimulus intensity and there is temporal summation of EPSPs evoked by paired PAG shocks. At condition-test intervals of 40-90 ms, train stimulation of PAG suppresses the tooth pulp-evoked EPSP in raphe neurons. The threshold for EPSP suppression occurs at a PAG stimulation intensity below that required for suppression of the JOR. The present findings provide evidence that RM neurons may play an important role in the modulation of the tooth pulp-evoked JOR, but only after the initial withdrawal reflex has occurred.     

Comparative study of sympathetic and parasympathetic discharges in the autonomic nerves during stimulation of different structures of the cat hypothalamus

Simultaneous recordings of hypothalamo-parasympathetic and hypothalamo-sympathetic evoked discharges in anesthetized cats demonstrated that both parasympathetic discharges in the pelvic nerve and sympathetic discharges in the splanchnic nerve of the lowest threshold and shortest latency could be obtained from stimulation of the posterior hypothalamus. The focus of the maximal neuronal activated elicited by stimulation of afferent fibres of visceral nerves and the focus evoking maximal efferent reactions of parasympathetic and sympathetic nerves were located in the same region of the postero-lateral hypothalamus. It is supposed (as a working hypothesis) that convergent polysensory neurons of the hypothalamus are also polyeffector divergent elements of the hypothalamo-visceral reflex system.