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![Example showing the location of pelvic nerve (PN)-responsive medullary reticular formation (MRF) neurons in 6 animals [3 intact male rats, 8 electrode tracks total; 3 rats with a chronic dorsal column lesion (DCx), 8 electrode tracks in total]. All of these neurons also responded to bilateral electrical stimulation of the dorsal nerve of the penis (DNP). Location of responses to low (stroke) and high (pinch) threshold levels of mechanical stimulation of the penis are shown in A. Responses to stroking the penis were only found in intact controls and sham-DCx (data not shown) animals. Some of the neurons shown in A also responded to colon distention (B). Note that although more PN-responsive neurons are shown post-DCx, there were no significant differences overall between the groups in the number of PN-responsive neurons per electrode track. Cross-section is adapted from Fig. 65 of Paxinos and Watson (1998). Intact data have been published elsewhere (Hubscher et al. 2004). 4V, 4th ventricle; 7, facial nucleus; DPGi, dorsal paragigantocellular nucleus; Gi, gigantocellular reticular nucleus; GiA, Gi pars alpha; IRt, intermediate reticular nucleus; LPGi, lateral paragigantocellular nucleus; py, pyramidal tract; RMg, raphe magnus nucleus.](profile/Charles-Hubscher-2/publication/8428237/figure/fig1/AS:394490222268419@1471065206909/Example-showing-the-location-of-pelvic-nerve-PN-responsive-medullary-reticular.png)
Example showing the location of pelvic nerve (PN)-responsive medullary reticular formation (MRF) neurons in 6 animals [3 intact male rats, 8 electrode tracks total; 3 rats with a chronic dorsal column lesion (DCx), 8 electrode tracks in total]. All of these neurons also responded to bilateral electrical stimulation of the dorsal nerve of the penis (DNP). Location of responses to low (stroke) and high (pinch) threshold levels of mechanical stimulation of the penis are shown in A. Responses to stroking the penis were only found in intact controls and sham-DCx (data not shown) animals. Some of the neurons shown in A also responded to colon distention (B). Note that although more PN-responsive neurons are shown post-DCx, there were no significant differences overall between the groups in the number of PN-responsive neurons per electrode track. Cross-section is adapted from Fig. 65 of Paxinos and Watson (1998). Intact data have been published elsewhere (Hubscher et al. 2004). 4V, 4th ventricle; 7, facial nucleus; DPGi, dorsal paragigantocellular nucleus; Gi, gigantocellular reticular nucleus; GiA, Gi pars alpha; IRt, intermediate reticular nucleus; LPGi, lateral paragigantocellular nucleus; py, pyramidal tract; RMg, raphe magnus nucleus.
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Single medullary reticular formation (MRF) neurons receive multiple somatovisceral convergent inputs originating from many different spinal and cranial nerves, including the pelvic nerve (PN), dorsal nerve of the penis (DNP), and the abdominal branches of the vagus. In a previous study, the input to MRF from the male genitalia was shown to be elimi...
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... summary showing the location of the PN-responsive neurons for three animals with DCx lesions at one anterior- posterior level within the restricted search area is shown in Fig. 1A. The results from intact control animals ( Hubscher et al. 2004) are also shown (for comparison). As shown in Fig. 1, these neurons were located throughout the MRF search area (in Gi, GiA, DPGi, LPGi; Paxinos and Watson ...
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... summary showing the location of the PN-responsive neurons for three animals with DCx lesions at one anterior- posterior level within the restricted search area is shown in Fig. 1A. The results from intact control animals ( Hubscher et al. 2004) are also shown (for comparison). As shown in Fig. 1, these neurons were located throughout the MRF search area (in Gi, GiA, DPGi, LPGi; Paxinos and Watson ...
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... occasion- ally had opposite responses (inhibitory or excitatory, respec- tively) from stimulation of one of the convergent territories, particularly the face. These neuronal response patterns, found on occasion in both controls and DCx lesioned animals, were located in all MRF subdivisions within the search territory (see outlined areas in Fig. 1). Two examples obtained from record- ings in the MRF of an intact control animal are provided in Fig. 3 (see also data in Table 1). A summary showing the location of neurons responding to colon distention in three DCx animals is also presented in Fig. 1B. No significant differences (P 0.05) were found between groups for convergent ...
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... were located in all MRF subdivisions within the search territory (see outlined areas in Fig. 1). Two examples obtained from record- ings in the MRF of an intact control animal are provided in Fig. 3 (see also data in Table 1). A summary showing the location of neurons responding to colon distention in three DCx animals is also presented in Fig. 1B. No significant differences (P 0.05) were found between groups for convergent input from the distal colon. Although no significant differences (P 0.05; see Table 1) were found across groups for responses to vagal stimulation (P 0.05), the mean vagal response latency for the DCx group (305.1 33.4 ms) was significantly different (t-test; ...
Citations
... ) , urethral stimulation , and stroke / pinch of the hind limbs ( Hubscher et al . 2004 ; Kaddumi & Hubscher , 2006 , 2007 ) . ...
... Intact and bDC – from Hubscher & Johnson , 2004 ; Hubscher et al . 2004 ...
... previously ( Hubscher & Johnson , 2004 ) for intact control rats and those with DC - only lesions is provided in Fig . 1 ( adapted from Paxinos & Watson , 1998 ) . Responses to stimulation of other somatovisceral territories , however , remained unchanged ( see Table 1 ) . ...
The specific white matter location of all the spinal pathways conveying penile input to the rostral medulla is not known. Our previous studies using rats demonstrated the loss of low but not high threshold penile inputs to medullary reticular formation (MRF) neurons after acute and chronic dorsal column (DC) lesions of the T8 spinal cord and loss of all penile inputs after lesioning the dorsal three-fifths of the cord. In the present study, select T8 lesions were made and terminal electrophysiological recordings were performed 45-60 days later in a limited portion of the nucleus reticularis gigantocellularis (Gi) and Gi pars alpha. Lesions included subtotal dorsal hemisections that spared only the lateral half of the dorsal portion of the lateral funiculus on one side, dorsal and over-dorsal hemisections, and subtotal transections that spared predominantly just the ventromedial white matter. Electrophysiological data for 448 single unit recordings obtained from 32 urethane-anaesthetized rats, when analysed in groups based upon histological lesion reconstructions, revealed (1) ascending bilateral projections in the dorsal, dorsolateral and ventrolateral white matter of the spinal cord conveying information from the male external genitalia to MRF, and (2) ascending bilateral projections in the ventrolateral white matter conveying information from the pelvic visceral organs (bladder, descending colon, urethra) to MRF. Multiple spinal pathways from the penis to the MRF may correspond to different functions, including those processing affective/pleasure/motivational, nociception, and mating-specific (such as for erection and ejaculation) inputs.
... This stimulus activates nerve fibers in the Aβ and Aδ range (Johnson and Murray, 1992). The abdominal branch of the vagus nerve was stimulated with a bipolar electrode introduced with the esophageal thermistor to access the portion of the nerve located on the external wall of the esophagus (Hubscher et al., 2004; Kaddumi and Hubscher, 2006). The stimulus intensity was set at 8 mA for 2 ms duration. ...
... However, if a spontaneously firing neuron was encountered and found to be non-responsive to PN stimulation, data from the neuron was included in the study if it responded to stimulation of the DNC. A neuron was considered responsive if the response to stimulation of a peripheral region/nerve was at least two times (excitation) or one-half (inhibition) the background activity (Chadha and Hubscher, 2008; Hubscher and Johnson, 2004). For nonspontaneous units, a minimum of 3 spikes/s was required to consider them as excitatory (Chadha and Hubscher, 2008; Hubscher and Johnson, 2004). ...
... A neuron was considered responsive if the response to stimulation of a peripheral region/nerve was at least two times (excitation) or one-half (inhibition) the background activity (Chadha and Hubscher, 2008; Hubscher and Johnson, 2004). For nonspontaneous units, a minimum of 3 spikes/s was required to consider them as excitatory (Chadha and Hubscher, 2008; Hubscher and Johnson, 2004). Upon finding a single neuron responsive to the PN and/or DNC, each neuron in all rats was further tested in the following sequence: vagus nerve stimulation, cervix stimulation , vaginal canal distension, colon distension and mechanical stimulation of the perineal region and other somatic areas. ...
Subfertility and severe pelvic pains are symptoms associated with endometriosis (ENDO), a common condition among women that is characterized by the growth of the uterine endometrium on the surface of organs within the pelvic region and abdominal cavity. The contribution of the CNS to symptoms associated with ENDO is not known. In the present study, the preoptic area (POA) of the hypothalamus was investigated, as this region of the forebrain is known to play an important role in the neuroendocrine control of the reproductive cycle, mating behavior, and antinociception. Female rats were either induced for ENDO by autotransplantation of uterine tissue (n=20) or uterine fat for surgical sham controls (n=11). Terminal extracellular electrophysiological recordings (urethane anesthesia) were conducted in the POA six weeks post-ENDO induction when the rats were in either the proestrus or metestrus stages of their estrous cycle. Significant differences were found between the ENDO versus SHAM groups of animals for the proportion of inhibitory responses as well as the percentage of neurons responding to stimulation of the abdominal branches of the vagus, which innervates portions of the female reproductive tract, including the ovaries. The endometriotic cysts were found to be significantly larger in proestrus rats (stage when hormones are elevated). These data demonstrate that the responses of POA neurons are influenced by the presence of endometriotic cysts in the abdominal cavity. Since the POA is known to be part of the neural circuitries that mediate nociception and fertility, any deviation from its normal activity under ENDO conditions could contribute to the constellation of symptoms that ensue.
... Distention of the urinary bladder in humans has been shown to produce contractions of the anal sphincter (Basinski et al., 2003). The convergence of visceral afferent inputs within the CNS contributes to the interactions between different pelvic visceral organs (Berkley, 2005; Kaddumi and Hubscher, 2006; Qin and Foreman, 2004). Using electrophysiological techniques, viscero-visceral convergence onto single spinal cord neurons has been shown in rats (Berkley et al., 1993; Qin and Foreman, 2004), cats (Foreman et al., 1984) and primates (Milne et al., 1981). ...
... This electrical nerve stimulus is sufficient to activate fibers in the Aβ and Aδ range (Kitchell et al., 1982). A bipolar electrode was inserted alongside the esophageal probe just caudal to the esophageal hiatus in order to stimulate the abdominal branches of the vagus nerve, which are situated on the external wall of the esophagus (Hubscher et al., 2004; Khasar et al., 1998). The stimulus intensity was set at 8 mA (0.5 trains/s, 2 ms duration). ...
... The stimulus intensity was set at 8 mA (0.5 trains/s, 2 ms duration). This stimulus intensity produces compound action potentials in the vagus nerve, as recorded with bipolar hook electrodes in the neck where the vagus runs along the common carotid artery (Hubscher et al., 2004). A midline abdominal incision was made to expose the UB and proximal urethra. ...
A number of clinical studies indicate the coexistence of multiple chronic pelvic diseases and pain syndromes. An association between various conditions related to the pelvic viscera may relate to a high degree of central visceral convergence, which is a requisite for the cross-organ coordination that is necessary for their normal functions. In the present study, a population of neurons receiving a high degree of somatovisceral convergence (those in the medullary reticular formation--MRF) was targeted in order to examine the effect of infusing a chemical irritant into one organ on the responsiveness of convergent inputs from various visceral and somatic regions of the body, using electrophysiological techniques. Acute irritation of the urinary bladder (UB) with 2% acetic acid significantly decreased the percentage of convergent MRF neuronal responses to UB distention and urethral infusion and significantly increased the percentage responding to whole body, mainly due to stimulation of the face. Irritation also produced a significant increase in the response duration of MRF neurons to distention of colon as well as the bladder (for those few UB responses that still remained). These results indicate that a pelvic/visceral pathology confined to one organ can affect at least some of the convergent responses from other regions of the body. The findings suggest that MRF neurons contribute to the cross-talk between different regions of the body under both normal and pathological conditions.
... For example, electrophysiological studies on rats showed that single neurons in the medullary reticular formation (123) and different thalamic subnuclei (124) respond to electrical stimulation of the dorsal nerve of the penis and mechanical stimulation of penis, including pinch. The location of ascending spinal projections includes pathways located in the dorsal half of the spinal cord (1,139,140). ...
... Specially fabricated bipolar silicon cuff microelectrodes were placed bilaterally around the PN and DNC (Hubscher and Johnson, 1996). For the abdominal branch of the vagus nerve, a bipolar ring electrode was threaded down the esophagus and positioned in the abdominal cavity just caudal to the esophageal hiatus (Hubscher et al., 2004; Khasar et al., 1998). This is the location of the abdominal branch, which lies on the outside of the mucosa (stimulating through the mucosa), which is activated with an 8 mA stimulus (0.5 trains per second, 2 ms duration). ...
... A response was noted if the number of spikes fired to a given stimulus was at least two times (excitation) or half (inhibition) of background levels (immediately prior to stimulus onset) based on digital oscilloscope records. The doubling/halving criteria was chosen because the increase/ decrease was clearly audible through the audio monitor and is clearly distinguishable as a response in comparison to the random and slight increases/decreases in firing frequency that are not associated with a stimulus (Hubscher and Johnson, 2004). A minimum of 3 spikes was required for units that did not have a spontaneous discharge in order to count them as excitatory. ...
... Spontaneous firing rates were measured from oscilloscope records using established protocols (Hubscher and Johnson, 2003, 2004). Single MRF neurons responding with both excitation and inhibition to stimulation of different somatovisceral convergent regions were noted and classified as having " complex " response patterns (as in Hubscher and Johnson, 2004). ...
The lordosis posture and cervix stimulation during copulation are important reproductive events involving complex neural circuitries that are under hormonal influence. An important component of this circuitry, neurons within the medullary reticular formation (MRF), was examined in the present study using electrophysiological techniques. Single unit extracellular recordings were performed in the MRF of 27 urethane-anesthetized female rats. Using bilateral electrical stimulation of the dorsal nerve of the clitoris as the search stimulus, a detailed examination of the somatovisceral convergent responses of 585 individual MRF neurons was made. A total of 7 different groups of cycling and ovariectomized/hormone-supplemented rats were examined and their neuronal response properties to mechanical stimulation of various pelvic organs (cervix pressure, vaginal distension, colon distension) compared. The results indicate the existence of complex response properties as well as several variations in MRF response characteristics that are hormone-dependent. Specifically, estradiol is associated with hyposensitivity to cervix pressure and hypersensitivity to stroking the face. These opposing effects of estradiol in the same subset of neurons likely relate to lordosis behavior which can be either disrupted or elicited, depending on the area being stimulated (upper versus lower parts of the body, respectively).
... MRF neurons, for example, that are responsive to electrical stimulation of dorsal nerve of penis (DNP) and mechanical stimulation of penis (low-and high-threshold stimuli) also respond to electrical stimulation of the pelvic nerve (PN), as well as to mechanical stimulation of the perineum and limbs (Hubscher & Johnson, 1996). Previous neuroanatomical and electrophysiological studies have, however, focused primarily on either inputs to MRF from territories involved with one pelvic organ system (such as from either the bladder and urethra or from the colon and rectum or from the genitalia) or on somato-visceral convergence (Roy et al. 1992; Hubscher & Johnson, 1996, 2004; Almeida & Lima, 1997; Nadelhaft & Vera, 2001; Hubscher et al. 2004). Given the vast array of inputs that have been shown to go to the MRF from the pelvic viscera, as well as convergent inputs from widespread somatic territories, it is hypothesized that there is a significant degree of overlap from different pelvic territories onto individual MRF neurons. ...
... The stimulus intensity, for both nerves, was set at 30–50 μA, 0.1 ms duration, with trains of 14 pulses at 70 pulses s −1 , 100 ms train duration, 1 train s −1 (Hubscher & Johnson, 1996). A bipolar electrode was introduced alongside the oesophageal thermometer probe, just caudal to the oesophageal hiatus, in order to stimulate the abdominal branches of the vagus nerve that are situated on the external wall of the oesophagus (Hubscher et al. 2004). The stimulus intensity was set at 8 mA for 2 ms duration. ...
... The stimulus intensity was set at 8 mA for 2 ms duration. This stimulus intensity produces compound action potentials in the vagus nerve, as recorded with bipolar hook electrodes in the neck where the vagus runs along the common carotid artery (Hubscher et al. 2004). ...
Electrophysiological recordings were used to investigate the degree of pelvic/visceral convergent inputs onto single medullary reticular formation (MRF) neurons. A total of 94 MRF neurons responsive to bilateral electrical stimulation of the pelvic nerve (PN) in 12 urethane-anaesthetized male rats were tested for responses to mechanical stimulation of the urinary bladder, urethra, colon and penis, and electrical stimulation of the dorsal nerve of the penis (DNP) and abdominal branches of the vagus. Responses to distension of the bladder were found for 51% (n = 48) of the MRF neurons tested. Of these 48, 71% responded to urethral infusion, 81% responded to colon distension, 100% responded to penile stimulation (and DNP), and 85% responded to vagal stimulation, with 62% responding to stimulation of all four of these territories. This high degree of visceral convergence (i.e. 62%) in a subset of PN-responsive MRF neurons is significantly greater than for the subset of PN-responsive MRF neurons that did not respond to urinary bladder distension (i.e. out of the 46 remaining neurons, none responded to all four of the other pelvic/visceral stimuli combined). These results suggest that the neurons processing information from the urinary bladder at this level of the neural axis are likely to be important for mediating interactions between different visceral organs for the coordination of multiple pelvic/visceral functions.
Despite common co-morbidity of sexual and urinary dysfunctions, the interrelationship between the neural control of these functions are poorly understood. The medullary reticular formation (MRF) contributes to both mating/arousal functions and micturition, making it a good site to test circuitry interactions. Urethane-anesthetized adult Wistar rats were used to examine the impact of electrically stimulating different nerve targets (dorsal nerve of the penis or clitoris - DNP / DNC; L6/S1 trunk) on responses of individual, extracellular-recorded MRF neurons. The effect of bladder filling on MRF neurons was also examined as was stimulation of DNP on bladder reflexes via cystometry. In total, 236 MRF neurons responded to neurostimulation: 102 to DNP stimulation (12 males), 64 to DNC stimulation (12 females), and 70 to L6/S1 trunk stimulation (12 males). Amplitude thresholds were significantly different at DNP (15.0 ± 0.6 µA), DNC (10.5 ± 0.7 µA) and L6/S1 trunk (54.2 ± 4.6 µA), whereas similar frequency responses were found (max responses near 30-40 Hz). In 5 males, filling/voiding cycles were lengthened with DNP stimulation (11.0 ± 0.9 µA), with a maximal effective frequency plateau beginning at 30 Hz. Bladder effects lasted around two minutes after DNP stimulus offset. Many MRF neurons receiving DNP/DNC input responded to bladder filling (35.0% and 68.3%, respectively), either just before (43%) or simultaneously with (57%) the voiding reflex. Taken together, MRF-evoked responses with neurostimulation of multiple nerve targets along with different responses to bladder infusion has implications for the role of MRF in multiple aspects of urogenital functions.
Male sexual responses are reflexes mediated by the spinal cord and modulated by neural circuitries involving both the peripheral and central nervous system. While the brain interact with the reflexes to allow perception of sexual sensations and to exert excitatory or inhibitory influences, penile reflexes can occur despite complete transections of the spinal cord, as demonstrated by the reviewed animal studies on spinalization and human studies on spinal cord injury. Neurophysiological and neuropharmacological substrates of the male sexual responses will be discussed in this review, starting with the spinal mediation of erection and its underlying mechanism with nitric oxide (NO), followed by the description of the ejaculation process, its neural mediation and its coordination by the spinal generator of ejaculation (SGE), followed by the occurrence of climax as a multisegmental sympathetic reflex discharge. Brain modulation of these reflexes will be discussed through neurophysiological evidence involving structures such as the medial preoptic area of hypothalamus (MPOA), the paraventricular nucleus (PVN), the periaqueductal gray (PAG), and the nucleus para-gigantocellularis (nPGI), and through neuropharmacological evidence involving neurotransmitters such as serotonin (5-HT), dopamine and oxytocin. The pharmacological developments based on these mechanisms to treat male sexual dysfunctions will complete this review, including phosphodiesterase (PDE-5) inhibitors and intracavernous injections (ICI) for the treatment of erectile dysfunctions (ED), selective serotonin reuptake inhibitor (SSRI) for the treatment of premature ejaculation, and cholinesterase inhibitors as well as alpha adrenergic drugs for the treatment of anejaculation and retrograde ejaculation. Evidence from spinal cord injured studies will be highlighted upon each step.
Thesis (Ph. D.)--University of Louisville, 2006. School of Medicine, Department of Anatomical Sciences and Neurobiology. Vita. "August 2006." Includes bibliographical references (leaves 144-161).
A recent survey of paraplegics indicates that regaining sexual function is of the highest priority for both males and females (Anderson, K.D. (2004) Targeting recovery: priorities of the spinal cord-injured population J. Newrotrauma, 21: 1371-1383). Our understanding of the neural pathways and mechanisms underlying sexual behavior and function is limited at the present time. More studies are obviously needed to direct experiments geared toward developing effective therapeutic interventions. In this chapter, a review of studies on the processing of sensory inputs from the male and female reproductive organs is presented with a review of what is known about the location of ascending spinal pathways conveying this information. The effect of spinal cord injury on sexual function and the problems that ensue are discussed.
