Rostral Medullary Neurons Research Articles

M1294 Response Characteristics of Rostral Medullary Neurons to Colorectal and Esophageal Distension in Cats

M1294 Response Characteristics of Rostral Medullary Neurons to Colorectal and Esophageal Distension in Cats

Evidence for distributed processing during hypoxic stimulation by the brainstem cardiorespiratory network

Brainstem neural networks play an important integrative role in the regulation of respiratory and cardiovascular responses to hypoxia, but their organization remains poorly understood. We addressed the hypothesis that a distributed brainstem network, including rostral medullary neurons (RMNs) in the region of the retrotrapezoid nucleus, dorsolateral pons, raphé, and ventrolateral cardiorespiratory column (VRC), integrate central and peripheral chemoreceptor inputs. Data were obtained from decerebrate adult cats. We used multi‐electrode arrays to record from up to 118 neurons simultaneously. Firing rate responses were measured during hypoxia and stimulation of central chemoreceptors. Spike trains were also analyzed with respiratory and cardiac cycle triggered histograms and cross correlation. Results include: 1. Multiple cardiorespiratory rhythms in neurons responsive to hypoxic stimulation. 2. Co‐expression of distributed eupneic network activity present together with gasp patterns during recovery from severe brain hypoxia. 3. Reciprocal effective RMN‐VRC connectivity of neurons responsive to both hypoxia and hypercapnia. The results suggest a brainstem network architecture with connectivity that shapes the respiratory motor pattern via overlapping circuits that modulate central and peripheral chemoreceptor‐mediated influences on breathing.Supported by NS19814, NS46062

Urinary Bladder Irritation Alters Efficacy of Vagal Stimulation on Rostral Medullary Neurons in Chronic T8 Spinalized Rats

The presence of pelvic visceral inputs to neurons in the rostral medulla that are responsive to electrical stimulation of the abdominal branches of the vagus nerve (VAG-abd) was investigated in a complete chronic T8 spinal transection rat model. Using extracellular electrophysiological recordings from single medullary reticular formation (MRF) neurons, 371 neurons in 15 rats responsive to pinching the ear (search stimulus) were tested for somato-visceral and viscero-visceral convergent responses to stimulation of the following nerves/territories: VAG-abd, dorsal nerve of the penis, pelvic nerve, distention of urinary bladder and colon, penile stimulation, urethral infusion, and touch/pinch of the entire body surface. In addition to these mechanical and electrical stimuli, a chemical stimulus applied to the bladder was assessed as well. Of the total neurons examined, 205 were tested before and 166 tested beginning 20 min after application of a chemical irritant (2% acetic acid) to the urinary bladder (same rats used pre/post irritation). As with intact controls, many ear-responsive MRF neurons responded to the electrical stimulation of VAG-abd. Although MRF neuron responses failed to be evoked with direct (mechanical and electrical nerve) pelvic visceral stimuli, acute chemical irritation of the urinary bladder produced a significant increase in the number of MRF neurons responsive to stimulation of VAG-abd. The results of this study indicate a central effect that potentially relates to some of the generalized below level pelvic visceral sensations that have been documented in patients with complete spinal cord injury.

Estradiol-associated variation in responses of rostral medullary neurons to somatovisceral stimulation

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).

Ascending and descending brainstem neuronal activity during cystometry in decerebrate cats.

This study was undertaken to examine the distribution of pontomedullary neurons related to micturition or urine storage, as well as the connections between the pontine micturition center (PMC), medullary neurons, and the spinal cord. In decerebrate cats, extracellular recording of the rostral pontine and rostral medullary neurons was performed. Firing of each neuron was quantitated during cystometry. Connections between the PMC, medullary neurons, and the spinal cord (L1) were also examined electrophysiologically. Ninety-four neurons showed an increase or decrease of the firing rate during micturition. Units with an antidromic response to L1 stimulation and an increased firing rate were located in the nucleus locus coeruleus alpha (LCa; n = 8) corresponding to the PMC, and in the medial reticular formation (MRF) of the medulla (n = 14). Units showing a decreased firing rate were located in the nucleus reticularis pontis oralis (PoO; n = 26) and in the MRF (n = 11). The latencies of antidromic and orthodromic responses of the LCa units were longer than those of the PoO units. MRF neurons responded antidromically and/or orthodromically to stimulation of the PMC or L1. These results suggest that the pathway concerned with urine storage has a faster spinobulbospinal loop than the micturition reflex pathway and that rostral medullary neurons also play an important role in micturition and urine storage. There may be two descending pathways between the PMC and the spinal cord: both a direct pathway and one by means of medullary neurons.

Influence of levels of carbon dioxide and oxygen upon gasping in perfused rat preparation

In vivo, the augmenting pattern of integrated phrenic nerve discharge of eupnea is altered to the decrementing pattern of gasping in severe hypoxia or ischaemia. Identical alterations in phrenic discharge are found in perfused in situ preparations of the juvenile rat. In this preparation, gasping was produced by equilibration of the perfusate with various levels of carbon dioxide and oxygen. The duration of the phrenic burst, the interval between bursts and the burst amplitude were not significantly different following equilibration with 21–6%O 2 at 5% CO 2 or with 0–9% CO 2 at 6% O 2, with the exception that the burst amplitude was significantly greater in hypercapnic-hypoxia (9% CO 2 at 6% O 2). It is proposed that hypoxia-induced gasping results from the release of an endogenous pacemaker activity of rostral medullary neurons. This release is caused by cellular mechanisms that change the balance between membrane ionic currents. Moreover, these cellular mechanisms may be explicitly induced by alterations in the ionic and metabolic homeostasis.

Response to CO2 of neurons in the rostral ventral medulla in vitro

1. It has been hypothesized that CO2-sensitive neurons are located in the rostral ventral medulla. To demonstrate this at the cellular level, perforated patch-clamp recordings were made from rat medullary slices in vitro. The effect of respiratory acidosis/alkalosis on the electrophysiologic properties of neurons was studied by recording membrane potential while changing the CO2 of the bath solution and allowing pH to vary. 2. At baseline, most neurons in the rostral ventrolateral medulla (VLM) and rostral medullary raphe spontaneously fired repetitively at a regular rate (3.3 +/- 2.5 Hz, mean +/- SD) with a linear interspike ramp depolarization (n = 102 of 135). Spontaneous firing continued after synaptic blockade with high-magnesium, low-calcium solution (n = 14 of 15). Spontaneous firing of calcium spikes continued in tetrodotoxin (TTX; n = 13 of 13), but was blocked by TTX and cadmium (n = 4 of 4). 3. The effect of respiratory acidosis/alkalosis on neurons was examined by changing the CO2 of the bicarbonate-buffered bath solution within the range of 3-9%. Most neurons studied (n = 74 of 105) did not change their firing rate in response to this stimulus; however, some neurons were stimulated (n = 16) and other neurons were inhibited (n = 15) by increases in CO2. 4. In many CO2-stimulated neurons, the increase in firing rate caused by an increase in CO2 was associated with an increase in slope of the linear interspike ramp depolarization, whereas in many CO2-inhibited neurons the opposite occurred, i.e., an increase in CO2 resulted in a decrease in slope of the ramp depolarization. These changes occurred without a change in the level of afterhyperpolarization or spike threshold. 5. Whole cell patch-clamp recording invariably resulted in loss of spontaneous and stimulated repetitive firing over 10-40 min despite good resting potential, input resistance, and amplitude of single depolarization-evoked spikes. CO2 produced no change in membrane potential in neurons after rundown of repetitive firing. The loss of repetitive firing and CO2 sensitivity with whole cell recording required the use of perforated-patch recordings of membrane potential or cell-attached-patch recordings of spike transients to accurately study the baseline electrophysiologic properties and CO2 sensitivity of rostral medullary neurons. 6. Neuronal location was determined before each recording using direct visualization of living slices, and after some recordings using biocytin staining. CO2-stimulated and CO2-inhibited neurons were both found to have cell bodies in the rostral VLM, an area thought to contain central respiratory chemoreceptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Disinhibition of off-cells and antinociception produced by an opioid action within the rostral ventromedial medulla

Activation of neurons in the rostral ventral medulla, by electrical stimulation or microinjection of glutamate, produces antinociception. Microinjection of opioid compounds in this region also has an antinociceptive effect, indicating that opioids activate a medullary output neuron that exerts a net inhibitory effect on nociception. When given systemically in doses sufficient to produce antinocieeption, morphine produces distinct, opposing responses in two physiologically identifiable classes of rostral medullary neurons. “Off-cells” are activated, and have been proposed to inhibit nociceptive transmission. “On-cells” are invariably depressed, and may have a pro-nociceptive role. Although on-cell firing is also depressed by iontophoretically applied morphine, off-cells do not respond to morphine applied in this manner. The present study used local infusion of the μ-selective opioid peptide Tyr- d-Ala-Gly-MePhe-Gly-ol-enkephalin (DAMGO) within the rostral medulla to determine whether off-cells are activated by an opioid action within this region that is sufficient to produce a behaviorally measurable antinociception. Activity of on- and off-cells was recorded before and after local infusion of DAMGO noxious heat-evoked tail flick reflex was inhibited in 17 of 28 cases. On-cell firing was profoundly depressed, and this occurred irrespective of the antinociceptive effectiveness of the injection. Off-cells were activated following DAMGO microinjections, but only in experiments in which the tail flick reflex was inhibited. Both reflex inhibition and neuronal effects were reversed following systemic administration of naloxone. These observations thus confirm the role of the on-cell as the focus of direct opioid action within the rostral medulla, and strongly support the proposal that disinhibition of off-cells is central to the antinociception actions of opioids within this region.

Morphology of rostral medullary neurons with intrinsic pacemaker activity in the rat

Neurons with regular ongoing activity attributable to intrinsic pacemaker properties were recorded in coronal tissue slices within the nucleus reticularis rostroventrolateralis of the rat medulla oblongata (RVL). The cells were injected with horseradish peroxidase or Lucifer yellow and their dendritic and proximal axonal characteristics were investigated ( n=15). These small-to-medium-sized neurons had a simple dendritic arborization (3–6 primary dendrites branching up to 3 times) apparently confined within the limits of nucleus RVL and with limited extension in the rostrocaudal direction. Their axons originated either from the cell body or from a primary dendrite and coursed in a dorsomedial direction without giving rise to lical arborizations. It is concluded that RVL pacemaker neurons, presumed to represent a non-adrenergic class of sympathoexcitatory premotor neurons, exhibit characteristics reminiscent of the archetypal ‘reticular core’ neurons.

Midbrain stimulation inhibits tail-flick only at currents sufficient to excite rostral medullary neurons

The effects of midbrain electrical stimulation on the activity of tail-flick (TF) related neurons in the rostral ventromedial medulla (RVM) were studied. Neurons whose activity either decreased (off-cells) or increased (on-cells) immediately prior to TF were examined. Of 31 off- and on-cells, 26 (84%) showed increased activity during midbrain stimulation sufficient to suppress the TF. Furthermore, in 21 of these cells, the threshold for activation was identical to the threshold for TF suppression, and in the other 5 cells the threshold difference was ⩽5 μA. This study provides evidence that off- and on-cells in the RVM mediate the antinociceptive actions of midbrain stimulation.