Abstract:
:Respiratory depression is a therapy-limiting side effect of opioid analgesics, yet our understanding of the brain circuits mediating this potentially lethal outcome remains incomplete. Here we studied the contribution of the rostral ventromedial medulla (RVM), a region long implicated in pain modulation and homeostatic regulation, to opioid-induced respiratory depression. Microinjection of the μ-opioid agonist DAMGO in the RVM of lightly anesthetized rats produced both analgesia and respiratory depression, showing that neurons in this region can modulate breathing. Blocking opioid action in the RVM by microinjecting the opioid antagonist naltrexone reversed the analgesic and respiratory effects of systemically administered morphine, showing that this region plays a role in both the analgesic and respiratory-depressant properties of systemically administered morphine. The distribution of neurons directly inhibited by RVM opioid microinjection was determined with a fluorescent opioid peptide, dermorphin-Alexa 594, and found to be concentrated in and around the RVM. The non-opioid analgesic improgan, like DAMGO, produced antinociception but, unlike DAMGO, stimulated breathing when microinjected into the RVM. Concurrent recording of RVM neurons during improgan microinjection showed that this agent activated RVM ON-cells, OFF-cells, and NEUTRAL-cells. Since opioids are known to activate OFF-cells but suppress ON-cell firing, the differential respiratory response to these two analgesic drugs is best explained by their opposing effects on the activity of RVM ON-cells. These findings show that pain relief can be separated pharmacologically from respiratory depression and identify RVM OFF-cells as important central targets for continued development of potent analgesics with fewer side effects.
journal_name
J Neurophysioljournal_title
Journal of neurophysiologyauthors
Phillips RS,Cleary DR,Nalwalk JW,Arttamangkul S,Hough LB,Heinricher MMdoi
10.1152/jn.00563.2012subject
Has Abstractpub_date
2012-11-01 00:00:00pages
2393-404issue
9eissn
0022-3077issn
1522-1598pii
jn.00563.2012journal_volume
108pub_type
杂志文章abstract::This study investigated the influence of different modalities of target information (visual, kinesthetic) on the accuracy, kinematics, and interjoint coordination of pointing movements to remembered targets. The targets were presented by a robot arm in five locations in three-dimensional (3D) space, either as a point ...
journal_title:Journal of neurophysiology
pub_type: 临床试验,杂志文章
doi:10.1152/jn.1998.79.6.2833
更新日期:1998-06-01 00:00:00
abstract::The dye Procion brown was used to identify in the light and electron microscope, synaptic contacts made between monosynaptically coupled neurons in the lamprey spinal cord whose synaptic interaction had been recorded. Synaptic contacts were made on different dendrites of the postsynaptic cell at different distances fr...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.1976.39.2.197
更新日期:1976-03-01 00:00:00
abstract::It is well known that pro- and antisaccades may deploy different cognitive processes. However, the specific reason why antisaccades have longer latencies than prosaccades is still under debate. In three experiments, we studied the factors contributing to the antisaccade cost by taking attentional orienting and target ...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.00815.2009
更新日期:2010-03-01 00:00:00
abstract::Cats were reared in total darkness from birth until 4-5 mo of age (DR cats, n = 7) or with very brief visual experience (1 or 2 days) during an otherwise similar period of dark rearing [DR(1) cats, n = 3; DR(2) cats, n = 7]. Single-cell recordings were made in area 17 of visual cortex at the end of this rearing period...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.1985.53.2.572
更新日期:1985-02-01 00:00:00
abstract::Procedural skill learning requires iterative comparisons between feedback of self-generated motor output and a goal sensorimotor pattern. In juvenile songbirds, neural representations of both self-generated behaviors (each bird's own immature song) and the goal motor pattern (each bird's adult tutor song) are essentia...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.00714.2018
更新日期:2019-02-01 00:00:00
abstract::1. B31 and B32 are pattern-initiator neurons in the buccal ganglia of Aplysia. Along with the B61/B62 neurons, B31/B32 are also motor neurons that innervate the 12 buccal muscle via the I2 nerve. This research was aimed at determining the physiological functions of the B31/B32 and B61/B62 neurons, and of the I2 muscle...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.1996.75.4.1309
更新日期:1996-04-01 00:00:00
abstract::Senosory neurons manifest pronounced changes in excitability during maturation, but the factors contributing to this ubiquitous developmental phenomenon are not well understood. To assess the contribution of intrinsic membrane properties to such changes in excitability, in the present study whole cell patch-clamp reco...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.1997.78.6.2895
更新日期:1997-12-01 00:00:00
abstract::During object manipulation, grip force is coordinated with load force, which is primarily determined by object kinematics. Proximal arm kinematics may affect grip force control, as proximal segment motion could affect control of distal hand muscles via biomechanical and/or neural pathways. The aim of this study was to...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.00227.2015
更新日期:2015-10-01 00:00:00
abstract::Facial flushing in rosacea is often induced by trigger events. However, trigger causation mechanisms are currently unclear. This study tested the central hypothesis that rosacea causes sympathetic and axon reflex-mediated alterations resulting in trigger-induced symptomatology. Twenty rosacea patients and age/sex-matc...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.00458.2015
更新日期:2015-09-01 00:00:00
abstract::1. Excitatory postsynaptic currents (EPSCs) in parasympathetic preganglionic neurons (PGNs) were examined by the use of the whole cell patch-clamp recording technique in slice preparations of the neonatal rat lumbosacral spinal cord. Synaptic responses were evoked in PGNs by extracellular stimulation of a neighboring ...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.1996.76.1.215
更新日期:1996-07-01 00:00:00
abstract::Cortical pyramidal cells are constantly bombarded by synaptic activity, much of which arises from other cortical neurons, both in normal conditions and during epileptic seizures. The action potentials generated by barrages of synaptic activity may exhibit a variable site of origin. Here we performed simultaneous whole...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.00922.2006
更新日期:2007-01-01 00:00:00
abstract::The transient receptor potential vanilloid-1 (TRPV1) receptor is involved in peripheral and spinal nociceptive processing and is a therapeutic target for pain. We have shown previously that TRPV1 in the ventrolateral periaqueductal gray (VL-PAG) tonically contributes to brain stem descending antinociception by stimula...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.91225.2008
更新日期:2009-05-01 00:00:00
abstract::Glass micropipettes were used to record the activity of 124 single units in the somatosensory vibrissa cortex (SI) of 16 rats in response to combined deflections of contralateral vibrissae. Compact multiangular electromechanical stimulators were used to stimulate individual vibrissal hairs alone or in combinations of ...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.1985.54.3.615
更新日期:1985-09-01 00:00:00
abstract::Histamine is a known secretagogue in adrenal chromaffin cells. Activation of G-protein linked H(1) receptors stimulates phospholipase C, which generates inositol trisphosphate leading to release of intracellular calcium stores and stimulation of calcium influx through store operated and other channels. This calcium le...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.2000.83.3.1435
更新日期:2000-03-01 00:00:00
abstract::The whole cell patch-clamp technique in combination with the slice preparation was used to investigate the electrophysiological properties of pigeon semicircular canal sensory and supporting cells. These properties were also characterized in regenerating neuroepithelia of pigeons preinjected with streptomycin to kill ...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.1997.78.4.1913
更新日期:1997-10-01 00:00:00
abstract::Many neurons in the dorsal region of the medial superior temporal area (MSTd) of monkey cerebral cortex respond to optic flow stimuli in which the center of motion is shifted off the center of the visual field. Each shifted-center-of-motion stimulus presents both different directions of planar motion throughout the vi...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.1997.77.2.782
更新日期:1997-02-01 00:00:00
abstract::We often look at and sometimes reach for visible targets. Looking at a target is fast and relatively easy. By comparison, reaching for an object is slower and is associated with a larger cost. We hypothesized that, as a result of these differences, abrupt visual onsets may drive the circuits involved in saccade planni...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.00968.2012
更新日期:2013-11-01 00:00:00
abstract::Spontaneous negative-going potentials occurring at an average frequency of 0.7 Hz were recorded from the dentate gyrus of slices prepared from the temporal hippocampus of young adult rats. These events (here termed "dentate waves") in several respects resembled the dentate spikes described for freely moving rats durin...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.00478.2004
更新日期:2004-12-01 00:00:00
abstract::Several studies have demonstrated that motor adaptations to a novel task environment can be transferred between limbs. Such interlimb transfer of motor commands is consistent with the notion of centrally driven strategies that can be generalized across different frames of reference. So far, studies of interlimb transf...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.00670.2011
更新日期:2012-08-01 00:00:00
abstract::1. Many cells in the superior temporal sulcus (STS) of the monkey that represent the foveal region of the visual field discharge during pursuit eye movements. Damage to these areas produces a deficit in the maintenance of pursuit eye movements when the target towards the side of the brain with the lesion. In the prese...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.1989.62.1.31
更新日期:1989-07-01 00:00:00
abstract::In this study we attempted to identify the principles that govern the changes in neural control that occur during repeated performance of a multiarticular coordination task. Eight participants produced isometric flexion/extension and pronation/supination torques at the radiohumeral joint, either in isolation (e.g., fl...
journal_title:Journal of neurophysiology
pub_type: 临床试验,杂志文章
doi:10.1152/jn.00670.2004
更新日期:2005-11-01 00:00:00
abstract::Beta-band oscillations are a dominant feature in the sensorimotor system, which includes movement-related beta desynchronization (MRBD) during the preparation and execution phases of movement and postmovement beta synchronization (PMBS) on movement cessation. Many studies have linked this rhythm to motor functions. Ho...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.00238.2020
更新日期:2020-08-01 00:00:00
abstract::Voice onset time (VOT) is an important parameter of speech that denotes the time interval between consonant onset and the onset of low-frequency periodicity generated by rhythmic vocal cord vibration. Voiced stop consonants (/b/, /g/, and /d/) in syllable initial position are characterized by short VOTs, whereas unvoi...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.1999.82.5.2346
更新日期:1999-11-01 00:00:00
abstract::Neurons in monkey orbitofrontal cortex (OF) are known to respond to reward-predicting cues with a strength that depends on the value of the predicted reward as determined 1) by intrinsic attributes including size and quality and 2) by extrinsic factors including the monkey's state of satiation and awareness of what ot...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.00373.2005
更新日期:2005-10-01 00:00:00
abstract::The functional maturation of cuneate neurons was studied using reproducible tactile stimulation procedures and quantitative assessment of coding capacities in anesthetized (N2O/O2 plus barbiturate infusion) or decerebrate cats from six different age groups; neonatal (1-5 days), 10-15, 25-30, 55-63, and 83-90 days, and...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.1984.52.1.86
更新日期:1984-07-01 00:00:00
abstract::Response properties of cells in the infragranular layers of cortical area 17 of the cat were examined in the absence of input from supragranular layers. Supragranular activity was silenced either reversibly by cooling the surface of cortex or permanently by making a cryogenic lesion of the supragranular layers. Visual...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.1986.56.4.1074
更新日期:1986-10-01 00:00:00
abstract::Whenever the eyes move, spatial attention must keep track of the locations of targets as they shift on the retina. This study investigated transsaccadic updating of visual attention to cued targets. While observers prepared a saccade, we flashed an irrelevant, but salient, color cue in their visual periphery and measu...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.00656.2012
更新日期:2013-03-01 00:00:00
abstract::The cholinergic system is critically involved in synaptic models of learning and memory by enhancing dendritic [Ca(2+)](i) signals. Diffuse cholinergic innervation suggests subcellular modulation of membrane currents and Ca(2+) signals. Here we use ion-selective microelectrodes to study spread of carbachol (CCh) after...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.1999.82.4.1909
更新日期:1999-10-01 00:00:00
abstract::The vestibuloocular reflex (VOR) needs to modulate its gain depending on target distance to prevent retinal slip during head movements. We investigated gain modulation (context compensation) for binocular gaze stabilization in human subjects during voluntary yaw and pitch head rotations. Movements of each eye were rec...
journal_title:Journal of neurophysiology
pub_type: 临床试验,杂志文章
doi:10.1152/jn.2000.84.6.2904
更新日期:2000-12-01 00:00:00
abstract::Several types of equilibrium point (EP) controllers have been proposed for the control of posture and movement. EP controllers are appealing from a computational perspective because they do not require solving the "inverse dynamic problem" (i.e., computation of the torques required to move a system along a desired tra...
journal_title:Journal of neurophysiology
pub_type: 杂志文章
doi:10.1152/jn.00983.2005
更新日期:2006-05-01 00:00:00