Physiological Properties of Raphe Magnus Neurons During  Sleep and Waking

Physiological properties of raphe magnus neurons during sleep and waking. Neurons in the medullary raphe magnus (RM) that are important in the descending modulation of nociceptive transmission are classified by their response to noxious tail heat as on,off, or neutral cells. Experiments in anesthetized animals demonstrate that RM on cells facilitate and off cells inhibit nociceptive transmission. Yet little is known of the physiology of these cells in the unanesthetized animal. The first aim of the present experiments was to determine whether cells with on- and off-like responses to noxious heat exist in the unanesthetized rat. Second, to determine if RM cells have state-dependent discharge, the activity of RM neurons was recorded during waking and sleeping states. Noxious heat applied during waking and slow wave sleep excited one group of cells (on-u) in unanesthetized rats. Other cells were inhibited by noxious heat (off-u) applied during waking and slow wave sleep states in unanesthetized rats. Neutral-u cells did not respond to noxious thermal stimulation applied during either slow wave sleep or waking. On-u and off-u cells were more likely to respond to noxious heat during slow wave sleep than during waking and were least likely to respond when the animal was eating or drinking. Although RM cells rarely respond to innocuous stimulation applied during anesthesia, on-u andoff-u cells were excited and inhibited, respectively, by innocuous somatosensory stimulation in the unanesthetized rat. The spontaneous activity of >90% of the RM neurons recorded in the unanesthetized rat was influenced by behavioral state. Off-u cells discharged sporadically during waking but were continuously active during slow wave sleep. By contrast,on-u and neutral-u cells discharged in bursts during waking and either ceased to discharge entirely or discharged at a low rate during slow wave sleep. We suggest that off cell discharge functions to suppress pain-evoked reactions during sleep, whereas on cell discharge facilitates pain-evoked responses during waking.

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The Effect of Unilateral Somatosensory Stimulation on Hemispheric Asymmetries During Slow Wave Sleep

SLEEP ◽

10.1093/sleep/27.1.63 ◽

2004 ◽

Vol 27 (1) ◽

pp. 63-68 ◽

Cited By ~ 8

Author(s):

Lisa A. Cottone ◽

David Adamo ◽

Nancy K. Squires

Keyword(s):

Slow Wave ◽

Slow Wave Sleep ◽

Hemispheric Asymmetries ◽

Somatosensory Stimulation

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Short-Duration Epileptic Discharges Show a Distinct Phase Preference During Ongoing Hippocampal Slow Oscillations

Journal of Neurophysiology ◽

10.1152/jn.00418.2010 ◽

2010 ◽

Vol 104 (4) ◽

pp. 2194-2202 ◽

Cited By ~ 7

Author(s):

Philip H. de Guzman ◽

Farhang Nazer ◽

Clayton T. Dickson

Keyword(s):

Short Duration ◽

Temporal Lobe ◽

Slow Wave ◽

Rem Sleep ◽

Slow Wave Sleep ◽

Epileptiform Activity ◽

Epileptic Activity ◽

Network Synchronization ◽

State Dependent ◽

Oscillatory Pattern

Non-REM (slow-wave) sleep has been shown to facilitate temporal lobe epileptiform events, whereas REM sleep seems more restrictive. This state-dependent modulation may be the result of the enhancement of excitatory synaptic transmission and/or the degree of network synchronization expressed within the hippocampus of the temporal lobe. The slow oscillation (SO), a ∼1 Hz oscillatory pattern expressed during non-REM sleep and urethane anesthesia, has been recently shown to facilitate the generation, maintenance, and propagation of stimulus-evoked epileptiform activity in the hippocampus. To further address the state-dependent modulation of epileptic activity during the SO, we studied the properties of short-duration interictal-like activity generated by focal application of penicillin in the hippocampus of urethane-anesthetized rats. Epileptiform spikes were larger but only slightly more prevalent during the SO as opposed to the theta (REM-like) state. More notably, however, epileptic spikes had a significant tendency to occur just following the peak negativity of ongoing SO cycles. Because of the known phase-dependent changes in 1) synaptic excitability (just following the positive peak of the SO) and 2) network synchronization (during the negative peak of the SO), these results suggest that it is the synchrony and not the changes in synaptic excitability that lead to the facilitation of epileptiform activity during sleep-like slow wave states.

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Activity of Murine Raphe Magnus Cells Predicts Tachypnea and On-Going Nociceptive Responsiveness

Journal of Neurophysiology ◽

10.1152/jn.00904.2007 ◽

2007 ◽

Vol 98 (6) ◽

pp. 3121-3133 ◽

Cited By ~ 11

Author(s):

Kevin M. Hellman ◽

Thaddeus S. Brink ◽

Peggy Mason

Keyword(s):

Discharge Rate ◽

Cell Types ◽

Noxious Stimulation ◽

Opioid Analgesia ◽

Cellular Mechanisms ◽

Noxious Heat ◽

Cell Discharge ◽

Opioid Administration ◽

Raphe Magnus ◽

On And Off Cells

In rats, opioids produce analgesia in large part by their effects on two cell populations in the medullary raphe magnus (RM). To extend our mechanistic understanding of opioid analgesia to the genetically tractable mouse, we characterized behavioral reactions and RM neural responses to opioid administration. d-Ala2, N-Me-Phe4-Gly5ol-enkephalin, a mu-opioid receptor agonist, microinjected into the murine RM produced cardiorespiratory depression and reduced slow wave electroencephalographic activity as well as increased the noxious heat-evoked withdrawal latencies. As in rat, RM cell types that were excited and inhibited by noxious stimuli, termed on and off cells, respectively, were observed in mice. However, in contrast to findings in rat, opioid doses that suppressed withdrawals did not alter the background discharge rate of murine on and off cells, suggesting that the cellular mechanisms by which the murine RM generates opioid analgesia are substantially different from those in rats. Murine on cell discharge did not predict the latency or magnitude of an ensuing withdrawal but did correlate to the magnitude and latency of concurrent withdrawals. Although opioids failed to alter the background discharge of on and off cells, they reduced the responses of RM neurons to noxious stimulation, further evidence that RM modulates on-going withdrawals. In characterizing the role of RM in respiratory modulation, we found that on cells burst and off cells paused during tachypneic events. The effects of opioids in the murine RM on homeostasis and the association of on and off cell discharge with tachypnea corroborate roles for opioid signaling in RM beyond analgesia.

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Impaired State-Dependent Potentiation of GABAergic Synaptic Currents Triggers Seizures in a Genetic Generalized Epilepsy Model

Cerebral Cortex ◽

10.1093/cercor/bhaa256 ◽

2020 ◽

Author(s):

Chun-Qing Zhang ◽

Mackenzie A Catron ◽

Li Ding ◽

Caitlyn M Hanna ◽

Martin J Gallagher ◽

...

Keyword(s):

Slow Wave ◽

Cortical Neurons ◽

Slow Wave Sleep ◽

Brain Slices ◽

Epileptic Activity ◽

Epilepsy Syndrome ◽

Synaptic Currents ◽

State Dependent ◽

Generalized Epilepsy

Abstract Epileptic activity in genetic generalized epilepsy (GGE) patients preferentially appears during sleep and its mechanism remains unknown. Here, we found that sleep-like slow-wave oscillations (0.5 Hz SWOs) potentiated excitatory and inhibitory synaptic currents in layer V cortical pyramidal neurons from wild-type (wt) mouse brain slices. In contrast, SWOs potentiated excitatory, but not inhibitory, currents in cortical neurons from a heterozygous (het) knock-in (KI) Gabrg2+Q/390X model of Dravet epilepsy syndrome. This created an imbalance between evoked excitatory and inhibitory currents to effectively prompt neuronal action potential firings. Similarly, physiologically similar up-/down-state induction (present during slow-wave sleep) in cortical neurons also potentiated excitatory synaptic currents within brain slices from wt and het KI mice. Moreover, this state-dependent potentiation of excitatory synaptic currents entailed some signaling pathways of homeostatic synaptic plasticity. Consequently, in het KI mice, in vivo SWO induction (using optogenetic methods) triggered generalized epileptic spike-wave discharges (SWDs), being accompanied by sudden immobility, facial myoclonus, and vibrissa twitching. In contrast, in wt littermates, SWO induction did not cause epileptic SWDs and motor behaviors. To our knowledge, this is the first mechanism to explain why epileptic SWDs preferentially happen during non rapid eye-movement sleep and quiet-wakefulness in human GGE patients.

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Serotonergic Raphe Magnus Cells That Respond to Noxious Tail Heat Are Not on or off Cells

Journal of Neurophysiology ◽

10.1152/jn.2000.84.4.1719 ◽

2000 ◽

Vol 84 (4) ◽

pp. 1719-1725 ◽

Cited By ~ 59

Author(s):

Keming Gao ◽

Peggy Mason

Keyword(s):

Neuronal Response ◽

Stimulus Onset ◽

Thermal Stimulation ◽

Evoked Responses ◽

Noxious Heat ◽

Nociceptive Transmission ◽

Raphe Magnus ◽

Pharmacological Studies ◽

Excitatory Responses ◽

Serotonin Immunoreactivity

Pharmacological studies have suggested that serotonergic cells in RM contribute to both the inhibition and facilitation of spinal nociceptive transmission. Physiological studies in the medullary nucleus raphe magnus (RM) and adjacent nucleus reticularis magnocellularis have identified putative nociceptive-inhibitory off cells and nociceptive-facilitatory neurons on cells by their responses to noxious thermal stimulation. The present study was designed to determine 1) whether any serotonergic RM cells respond to noxious thermal stimulation and 2) whether noxious heat-responsive serotonergic cells should be classified ason or off cells. Serotonergic cells ( n = 150) were identified by physiological criteria in anesthetized rats; 30 of 32 cells tested contained serotonin immunoreactivity. Noxious tail heat elicited a neuronal response in less than a quarter of the serotonergic cells. Most serotonergic cells that responded to tail heat were excited ( n = 25), while a small minority of the cells tested were inhibited ( n = 8). The tail heat-evoked responses of serotonergic cells were small in magnitude, averaging five to eight spikes in 10 s. Excitatory responses rarely persisted for more than 10 s, while inhibitory responses rarely persisted for more than 20 s. The tail heat-evoked responses of serotonergic cells were compared to those of non-serotonergic cells ( n = 186). Non-serotonergic cells that responded to noxious tail heat had significantly greater response magnitudes, averaging 75–95 spikes in 10 s, than heat-responsive serotonergic cells. In addition, most heat-responsive non-serotonergic cells responded for at least 30 s after stimulus onset. These results demonstrate that the tail heat-evoked responses of serotonergic RM cells are qualitatively and quantitatively distinct from those of non-serotonergic onand off cells. It is therefore unlikely that serotonergic RM cells, even the subpopulation that responds to noxious tail heat, share a physiological function with on and offcells.

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Human cortical–hippocampal dialogue in wake and slow-wave sleep

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1607289113 ◽

2016 ◽

Vol 113 (44) ◽

pp. E6868-E6876 ◽

Cited By ~ 46

Author(s):

Anish Mitra ◽

Abraham Z. Snyder ◽

Carl D. Hacker ◽

Mrinal Pahwa ◽

Enzo Tagliazucchi ◽

...

Keyword(s):

Cerebral Cortex ◽

Slow Wave ◽

Information Transfer ◽

Direct Evidence ◽

Slow Wave Sleep ◽

Declarative Memory ◽

Resting State Fmri ◽

Reverse Direction ◽

State Dependent ◽

Band Activity

Declarative memory consolidation is hypothesized to require a two-stage, reciprocal cortical–hippocampal dialogue. According to this model, higher frequency signals convey information from the cortex to hippocampus during wakefulness, but in the reverse direction during slow-wave sleep (SWS). Conversely, lower-frequency activity propagates from the information “receiver” to the “sender” to coordinate the timing of information transfer. Reversal of sender/receiver roles across wake and SWS implies that higher- and lower-frequency signaling should reverse direction between the cortex and hippocampus. However, direct evidence of such a reversal has been lacking in humans. Here, we use human resting-state fMRI and electrocorticography to demonstrate that δ-band activity and infraslow activity propagate in opposite directions between the hippocampus and cerebral cortex. Moreover, both δ activity and infraslow activity reverse propagation directions between the hippocampus and cerebral cortex across wake and SWS. These findings provide direct evidence for state-dependent reversals in human cortical–hippocampal communication.

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Sleep-Like States Modulate Functional Connectivity in the Rat Olfactory System

Journal of Neurophysiology ◽

10.1152/jn.00711.2010 ◽

2010 ◽

Vol 104 (6) ◽

pp. 3231-3239 ◽

Cited By ~ 31

Author(s):

Donald A. Wilson ◽

Xiaodan Yan

Keyword(s):

Functional Connectivity ◽

Olfactory Bulb ◽

Slow Wave ◽

Slow Wave Sleep ◽

Dorsal Hippocampus ◽

Piriform Cortex ◽

Field Potential ◽

Wave State ◽

State Dependent ◽

Hippocampal Activity

The present study was an examination of state-dependent functional connectivity during spontaneous activity between the piriform cortex and its upstream and downstream connections. Rats were anesthetized with urethan and allowed to spontaneously cycle between fast- and slow-wave states similar to fast- and slow-wave sleep states. Local field potential recordings were made from the olfactory bulb, piriform cortex, dorsal hippocampus, amygdala, and primary visual cortex. The results demonstrate that during slow-wave sleep-like states, when the piriform cortex shows reduced sensitivity to odor input via the olfactory bulb, there is enhanced coherence with other forebrain structures. Granger causality analyses suggest that the link between piriform cortical and hippocampal activity during slow-wave state is in the direction of the hippocampus to the piriform cortex rather than the reverse. The results suggest that slow-wave sleep-like states may provide an opportunity for the transfer and/or consolidation of information related to odor memories, specifically at a time when the piriform cortex is less sensitive to sensory input.

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