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Daniel S. Zahm - One of the best experts on this subject based on the ideXlab platform.
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ORIGINAL ARTICLE
2016Co-Authors: Daniel S. ZahmAbstract:Mesopontine rostromedial tegmental nucleus neurons projecting to the dorsal raphe and pedunculopontine tegmental nucleus: psychostimulant-elicited Fos expression and collateralizatio
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The Mesopontine rostromedial tegmental nucleus: an integrative modulator of the reward system
Basal ganglia, 2011Co-Authors: Heather N. Lavezzi, Daniel S. ZahmAbstract:The Mesopontine rostromedial tegmental nucleus (RMTg) is a newly discovered brain structure thought to profoundly influence reward-related pathways. The RMTg is prominently GABAergic, receives dense projections from the lateral habenula and projects strongly to the midbrain ventral tegmental area and substantia nigra compacta. It receives additional afferent connections from widespread brain structures and sends additional strong efferent connections to a number of non-dopaminergic brainstem structures and, to a lesser extent, the forebrain. Projection neurons of the RMTg have been shown to express Fos in response to aversive stimuli and/or reward omission and psychostimulant drug administration. This review will first recount how the RMTg was discovered and then describe in greater detail what is known about its neuroanatomical relationships, including afferent and efferent connections, neurotransmitters, and receptors. Finally, we will focus on what has been reported about its function.
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The caudal sublenticular region/anterior amygdaloid area is the only part of the rat forebrain and Mesopontine tegmentum occupied by magnocellular cholinergic neurons that receives outputs from the central division of extended amygdala
Brain research, 2002Co-Authors: Myriam Gastard, Sarah L. Jensen, John R. Martin, Evelyn A. Williams, Daniel S. ZahmAbstract:Ascending cholinergic projections and the central nucleus of the amygdala (CeA) have both been implicated in attentional and orienting mechanisms leading to adaptive behavioral responses. In view of this, the present study was carried out to identify relevant neuroanatomical relationships in the form of projections from the CeA and a related structure, the dorsolateral divison of the bed nucleus of the stria terminalis (dlBST), to parts of the basal forebrain and Mesopontine tegmentum that contain magnocellular cholinergic neurons. The CeA and dlBST are components of the 'central division of extended amygdala'. Following injections of the anterogradely transported compounds, Phaseolus vulgaris-leucoagglutinin or biotinylated dextran amine, into the CeA or dlBST, sections were processed with immunohistochemical reagents to localize the anterograde tracer and choline acetyltransferase (ChAT). The trajectories of efferent projections from CeA and dlBST were qualitatively similar. Few ChAT-immunoreactive (ir) neurons were present within the extended amygdala or regions containing the dense terminations of its efferent projections, with the striking exception of the caudal sublenticular/anterior amygdaloid region. The ChAT-ir neurons there, however, were significantly smaller and weakly ChAT-ir as compared to those located outside of the dense extended amygdaloid terminations. In the Mesopontine tegmentum, the robust downstream projection from the extended amygdala was centered medial to ChAT-ir neurons of the pedunculopontine tegmental nucleus. The differentiated character of the relationships between extended amygdala and forebrain and Mesopontine districts containing ChAT-ir neurons that give rise to ascending projections may have significant implications for the control of cortical and diencephalic acetylcholine release and accompanying effects on attention, vigilance and locomotor activation.
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the caudal sublenticular region anterior amygdaloid area is the only part of the rat forebrain and Mesopontine tegmentum occupied by magnocellular cholinergic neurons that receives outputs from the central division of extended amygdala
Brain Research, 2002Co-Authors: Myriam Gastard, Sarah L. Jensen, John R. Martin, Evelyn A. Williams, Daniel S. ZahmAbstract:Ascending cholinergic projections and the central nucleus of the amygdala (CeA) have both been implicated in attentional and orienting mechanisms leading to adaptive behavioral responses. In view of this, the present study was carried out to identify relevant neuroanatomical relationships in the form of projections from the CeA and a related structure, the dorsolateral divison of the bed nucleus of the stria terminalis (dlBST), to parts of the basal forebrain and Mesopontine tegmentum that contain magnocellular cholinergic neurons. The CeA and dlBST are components of the 'central division of extended amygdala'. Following injections of the anterogradely transported compounds, Phaseolus vulgaris-leucoagglutinin or biotinylated dextran amine, into the CeA or dlBST, sections were processed with immunohistochemical reagents to localize the anterograde tracer and choline acetyltransferase (ChAT). The trajectories of efferent projections from CeA and dlBST were qualitatively similar. Few ChAT-immunoreactive (ir) neurons were present within the extended amygdala or regions containing the dense terminations of its efferent projections, with the striking exception of the caudal sublenticular/anterior amygdaloid region. The ChAT-ir neurons there, however, were significantly smaller and weakly ChAT-ir as compared to those located outside of the dense extended amygdaloid terminations. In the Mesopontine tegmentum, the robust downstream projection from the extended amygdala was centered medial to ChAT-ir neurons of the pedunculopontine tegmental nucleus. The differentiated character of the relationships between extended amygdala and forebrain and Mesopontine districts containing ChAT-ir neurons that give rise to ascending projections may have significant implications for the control of cortical and diencephalic acetylcholine release and accompanying effects on attention, vigilance and locomotor activation.
Marshall Devor - One of the best experts on this subject based on the ideXlab platform.
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Reduced Sensitivity to Anesthetic Agents upon Lesioning the Mesopontine Tegmental Anesthesia Area in Rats Depends on Anesthetic Type
Anesthesiology, 2020Co-Authors: Anne Minert, Mark Baron, Marshall DevorAbstract:BACKGROUND The brainstem Mesopontine tegmental anesthesia area is a key node in circuitry responsible for anesthetic induction and maintenance. Microinjecting the γ-aminobutyric acid-mediated (GABAergic) anesthetic pentobarbital in this nucleus rapidly and reversibly induces general anesthesia, whereas lesioning it renders the animal relatively insensitive to pentobarbital administered systemically. This study investigated whether effects of lesioning the Mesopontine tegmental anesthesia area generalize to other anesthetic agents. METHODS Cell-selective lesions were made using ibotenic acid, and rats were later tested for changes in the dose-response relation to etomidate, propofol, alfaxalone/alfadolone, ketamine, and medetomidine delivered intravenously using a programmable infusion pump. Anesthetic induction for each agent was tracked using five behavioral endpoints: loss of righting reflex, criterion for anesthesia (score of 11 or higher), criterion for surgical anesthesia (score of 14 or higher), antinociception (loss of pinch response), and deep surgical anesthesia (score of 16). RESULTS As reported previously for pentobarbital, on-target Mesopontine tegmental anesthesia area lesions reduced sensitivity to the GABAergic anesthetics etomidate and propofol. The dose to achieve a score of 16 increased to 147 ± 50% of baseline in control animals ± SD (P = 0.0007; 7 lesioned rats and 18 controls) and 136 ± 58% of baseline (P = 0.010; 6 lesioned rats and 21 controls), respectively. In contrast, responsiveness to the neurosteroids alfaxalone and alfadolone remained unchanged compared with baseline (94 ± 24%; P = 0.519; 6 lesioned rats and 18 controls) and with ketamine increased slightly (90 ± 11%; P = 0.039; 6 lesioned rats and 19 controls). The non-GABAergic anesthetic medetomidine did not induce criterion anesthesia even at the maximal dose tested. The dose to reach the maximal anesthesia score actually obtained was unaffected by the lesion (112 ± 8%; P = 0.063; 5 lesioned rats and 18 controls). CONCLUSIONS Inability to induce anesthesia in lesioned animals using normally effective doses of etomidate, propofol, and pentobarbital suggests that the Mesopontine tegmental anesthesia area is the effective target of these, but not necessarily all, GABAergic anesthetics upon systemic administration. Cortical and spinal functions are likely suppressed by recruitment of dedicated ascending and descending pathways rather than by direct, distributed drug action.
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Location of the Mesopontine Neurons Responsible for Maintenance of Anesthetic Loss of Consciousness.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2017Co-Authors: Anne Minert, Shai-lee Yatziv, Marshall DevorAbstract:The transition from wakefulness to general anesthesia is widely attributed to suppressive actions of anesthetic molecules distributed by the systemic circulation to the cerebral cortex (for amnesia and loss of consciousness) and to the spinal cord (for atonia and antinociception). An alternative hypothesis proposes that anesthetics act on one or more brainstem or diencephalic nuclei, with suppression of cortex and spinal cord mediated by dedicated axonal pathways. Previously, we documented induction of an anesthesia-like state in rats by microinjection of small amounts of GABAA-receptor agonists into an upper brainstem region named the Mesopontine tegmental anesthesia area (MPTA). Correspondingly, lesioning this area rendered animals resistant to systemically delivered anesthetics. Here, using rats of both sexes, we applied a modified microinjection method that permitted localization of the anesthetic-sensitive neurons with much improved spatial resolution. Microinjected at the MPTA hotspot identified, exposure of 1900 or fewer neurons to muscimol was sufficient to sustain whole-body general anesthesia; microinjection as little as 0.5 mm off-target did not. The GABAergic anesthetics pentobarbital and propofol were also effective. The GABA-sensitive cell cluster is centered on a tegmental (reticular) field traversed by fibers of the superior cerebellar peduncle. It has no specific nuclear designation and has not previously been implicated in brain-state transitions. SIGNIFICANCE STATEMENT General anesthesia permits pain-free surgery. Furthermore, because anesthetic agents have the unique ability to reversibly switch the brain from wakefulness to a state of unconsciousness, knowing how and where they work is a potential route to unraveling the neural mechanisms that underlie awareness itself. Using a novel method, we have located a small, and apparently one of a kind, cluster of neurons in the Mesopontine tegmentum that are capable of effecting brain-state switching when exposed to GABAA-receptor agonists. This action appears to be mediated by a network of dedicated axonal pathways that project directly and/or indirectly to nearby arousal nuclei of the brainstem and to more distant targets in the forebrain and spinal cord.
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Mesopontine switch for the induction of general anesthesia by dedicated neural pathways
Anesthesia & Analgesia, 2016Co-Authors: Inna Sukhotinsky, Anne Minert, Peter Soja, Marshall DevorAbstract:We review evidence that the induction of anesthesia with GABAergic agents is mediated by a network of dedicated axonal pathways, which convey a suppressive signal to remote parts of the central nervous system. The putative signal originates in an anesthetic-sensitive locus in the brainstem that we refer to as the Mesopontine tegmental anesthesia area (MPTA). This architecture stands in contrast to the classical notion that anesthetic molecules themselves directly mediate anesthetic induction after global distribution by the vascular circulation. The MPTA came to light in a systematic survey of the rat brain as a singular locus at which microinjection of minute quantities of GABAergic anesthetics is able to reversibly induce a state resembling surgical anesthesia. The rapid onset of anesthesia, the observed target specificity, and the fact that effective doses are far too small to survive dilution during vascular redistribution to distant areas in the central nervous system are all incompatible with the classical global suppression model. Lesioning the MPTA selectively reduces the animal's sensitivity to systemically administered anesthetics. Taken together, the microinjection data show that it is sufficient to deliver γ-aminobutyric acid A receptor (GABAA-R) agonists to the MPTA to induce an anesthesia-like state and the lesion data indicate that MPTA neurons are necessary for anesthetic induction by the systemic route at clinically relevant doses. Known connectivity of the MPTA provides a scaffold for defining the specific projection pathways that mediate each of the functional components of anesthesia. Because MPTA lesions do not induce coma, the MPTA is not a key arousal nucleus essential for maintaining the awake state. Rather, it appears be a "gatekeeper" of arousal function, a major element in a flip-flop switching mechanism that executes rapid and reversible transitions between the awake and the anesthetic state.
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Bulbospinal neurons implicated in Mesopontine-induced anesthesia are substantially collateralized.
The Journal of comparative neurology, 2008Co-Authors: K Reiner, Inna Sukhotinsky, Marshall DevorAbstract:Microinjection of pentobarbital or other γ-aminobutyric acid type A receptor (GABAA-R) active anesthetics into a brainstem region in the rat that we have called the Mesopontine tegmental anesthesia area (MPTA) induces a general anesthesia-like state that includes suppression of locomotor activity, loss of the righting reflex, atonia, antinociception, and apparent loss of consciousness. The suppression of muscle tone and of nocifensive spinal reflexes suggests a direct or indirect effect at the level of the spinal cord itself, an inference supported by anterograde tracing from the MPTA area. We have now used single and double retrograde tracing to characterize this bulbospinal pathway further. The MPTA contains the majority of all bulbospinal neurons present at Mesopontine levels (65.8%). Many of these neurons, although not all, appear to have a highly collateralized projection pattern within the spinal cord. About 40% of the MPTA neurons that project to the lumbar spinal cord also have collaterals at cervical levels, and about 60% of those with projections to the ventral horn also have projections to the dorsal horn (at cervical levels). However, the large majority projects either ipsilaterally or contralaterally. Relatively few (∼13%) send collaterals to both sides of the spinal cord. The pattern of connectivity revealed appears to be consistent with a system designed primarily to modulate motor and sensory functions globally, over the entire neuraxis, rather than regionally or segmentally. J. Comp. Neurol. 508:418–436, 2008. © 2008 Wiley-Liss, Inc.
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reversible analgesia atonia and loss of consciousness on bilateral intracerebral microinjection of pentobarbital
Pain, 2001Co-Authors: Marshall Devor, Vladimir ZalkindAbstract:Abstract Concussion, asphyxia, and systemically administered general anesthetics all induce reversible depression of the organism's response to noxious stimuli as one of the elements of loss of consciousness. This is so even for barbiturate anesthetics, which have only modest analgesic efficacy at subanesthetic doses. Little is known about the neural circuits involved in this form of antinociception, although for anesthetic agents, at least, it is usually presumed that the drugs act in widely distributed regions of the nervous system. We now report the discovery of a focal zone in the brainstem Mesopontine tegmentum in rats at which microinjection of minute quantities of pentobarbital induces a transient, reversible anesthetic-like state with non-responsiveness to noxious stimuli, flaccid atonia, and absence of the righting reflex. The behavioral suppression is accompanied by slow-wave EEG and, presumably, loss of consciousness. This zone, which we refer to as the Mesopontine tegmental anesthesia locus (MPTA), apparently contains a barbiturate-sensitive ‘switch’ for both cortical and spinal activity. The very existence of the MPTA locus has implications for an understanding of the neural circuits that control motor functions and pain sensation, and for the cerebral representation of consciousness.
Christopher S. Leonard - One of the best experts on this subject based on the ideXlab platform.
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Direct and Indirect Excitation of Laterodorsal Tegmental Neurons by Hypocretin/Orexin Peptides: Implications for Wakefulness
2014Co-Authors: Sophie Burlet, Christopher J. Tyler, Christopher S. LeonardAbstract:Compelling evidence links the recently discovered hypotha-lamic peptides Hypocretin/Orexin (Hcrt/Orx) to rapid eye move-ment sleep (REM) control and the sleep disorder narcolepsy, yet how they influence sleep-related systems is not well under-stood. We investigated the action of Hcrt/Orx on Mesopontine cholinergic (MPCh) neurons of the laterodorsal tegmental nu-cleus (LDT), a target group whose function is altered in canine narcolepsy and appears pivotal for normal REM and wakeful-ness. Extracellular recordings from mouse brainstem slices revealed that Hcrt/Orx evoked prolonged firing of LDT neurons. Whole-cell recordings revealed that Hcrt/Orx had actions on both presynaptic neurons and at postsynaptic sites. Hcrt/Orx produced an increase in frequency and amplitude of sponta-neous EPSCs without equivalent effect on IPSCs, by triggering action potentials and enhancing spike-evoked synaptic trans
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hypocretin orexin receptor functions in Mesopontine systems regulating sleep arousal and cataplexy
2011Co-Authors: Christopher S. Leonard, Mike Kalogiannis, Kristi A KohlmeierAbstract:It is eminently clear from numerous chapters in this volume that the orexin (hypocretin) neuropeptides are necessary for the normal expression of waking and sleep. However, it remains fundamentally unclear how the absence of signaling by these peptides results in the symptoms of narcolepsy. Which of the many neurons bearing orexin receptors are necessary to sustain normal waking and sleep, and which of the numerous orexin actions are required for these processes? Does the simple loss of orexin’s excitatory actions produce narcolepsy, or are there more subtle aspects to the loss of orexin signaling that result in plastic or trophic changes that give rise to the symptoms of narcolepsy and cataplexy?
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Urotensin II acts as a modulator of Mesopontine cholinergic neurons.
Brain research, 2005Co-Authors: S D Clark, H P Nothacker, Christopher S. Leonard, Charles D. Blaha, Christopher J. Tyler, Dee M. Duangdao, Stephen L. Grupke, David R. Helton, O CivelliAbstract:Urotensin II (UII) is a vasomodulatory peptide that was not predicted to elicit CNS activity. However, because we have recently shown that the urotensin II receptor (UII-R) is selectively expressed in rat Mesopontine cholinergic (MPCh) neurons, we hypothesize that UII may have a central function. The present study demonstrates that the UII system is able to modulate MPCh neuron activity. Brain slice experiments demonstrate that UII excites MPCh neurons of the mouse laterodorsal tegmentum (LDTg) by activating a slow inward current. Furthermore, microinfusion of UII into the ventral tegmental area produces a sustained increase in dopamine efflux in the nucleus accumbens, as measured by in vivo chronoamperometry. In agreement with UII activation of MPCh neurons, intracerebroventricular injections of UII significantly modulate ambulatory movements in both rats and mice but do not significantly affect startle habituation or prepulse inhibition. The present study establishes that UII is a neuromodulator that may be exploited to target disorders involving MPCh dysfunction.
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Activity-Dependent Nitric Oxide Concentration Dynamics in the Laterodorsal Tegmental Nucleus In Vitro
Journal of neurophysiology, 2001Co-Authors: Christopher S. Leonard, E. K. Michaelis, K. M. MitchellAbstract:The behavioral-state related firing of Mesopontine cholinergic neurons of the laterodorsal tegmental nucleus appears pivotal for generating both arousal and rapid-eye-movement sleep. Since these ne...
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Serotonergic inhibition of action potential evoked calcium transients in NOS-containing Mesopontine cholinergic neurons.
Journal of neurophysiology, 2000Co-Authors: Christopher S. Leonard, Sanjai R. Rao, Takafumi InoueAbstract:Nitric oxide synthase (NOS)-containing Mesopontine cholinergic (MPCh) neurons of the laterodorsal tegmental nucleus (LDT) are hypothesized to drive the behavioral states of waking and REM sleep thr...
O Civelli - One of the best experts on this subject based on the ideXlab platform.
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Urotensin II acts as a modulator of Mesopontine cholinergic neurons.
Brain research, 2005Co-Authors: S D Clark, H P Nothacker, Christopher S. Leonard, Charles D. Blaha, Christopher J. Tyler, Dee M. Duangdao, Stephen L. Grupke, David R. Helton, O CivelliAbstract:Urotensin II (UII) is a vasomodulatory peptide that was not predicted to elicit CNS activity. However, because we have recently shown that the urotensin II receptor (UII-R) is selectively expressed in rat Mesopontine cholinergic (MPCh) neurons, we hypothesize that UII may have a central function. The present study demonstrates that the UII system is able to modulate MPCh neuron activity. Brain slice experiments demonstrate that UII excites MPCh neurons of the mouse laterodorsal tegmentum (LDTg) by activating a slow inward current. Furthermore, microinfusion of UII into the ventral tegmental area produces a sustained increase in dopamine efflux in the nucleus accumbens, as measured by in vivo chronoamperometry. In agreement with UII activation of MPCh neurons, intracerebroventricular injections of UII significantly modulate ambulatory movements in both rats and mice but do not significantly affect startle habituation or prepulse inhibition. The present study establishes that UII is a neuromodulator that may be exploited to target disorders involving MPCh dysfunction.
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The urotensin II receptor is expressed in the cholinergic Mesopontine tegmentum of the rat.
Brain research, 2001Co-Authors: S D Clark, H P Nothacker, Z Wang, Y Saito, F M Leslie, O CivelliAbstract:Urotensin II (UII) is a peptide known to be a potent vasoconstrictor. The urotensin II receptor (UII-R) is expressed not only in peripheral tissues but also in the brain of rodents. As a basis for studies of UII central nervous system actions, UII-R localization in the rat brain was analyzed by in situ hybridization and by in situ binding. UII-R mRNA was found in the Mesopontine tegmental area colocalizing with choline acetyltransferase. Binding sites were detected throughout the brain with the highest levels found in the pedunculopontine tegmental area, the lateral dorsal tegmental area, and the lateral septal, medial habenular, and interpeduncular nuclei. The majority of these brain nuclei are sites of axonal termination originating from the Mesopontine areas, suggesting that UII-R is a presynaptic receptor. This distribution of UII-R in the cholinergic Mesopontine area indicates that the UII system may be involved in sensory-motor integration and perhaps in central nervous system blood flow.
Peter B Reiner - One of the best experts on this subject based on the ideXlab platform.
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are Mesopontine cholinergic neurons either necessary or sufficient components of the ascending reticular activating system
Seminars in Neuroscience, 1995Co-Authors: Peter B ReinerAbstract:Abstract The reticular activating system is thought to be composed of one or more thalamo-cortical afferents whose activation results in desynchronization of the electroencephalogram. In recent years, a strong body of correlative evidence has accumulated suggesting that Mesopontine cholinergic neurons are a key component of the reticular activating system. However, despite intense study, several critical predictions of the hypothesis remain unfulfilled, and it is still not possible to conclude that Mesopontine cholinergic neuronal activity is either necessary or sufficient for generation of desynchrony. Specific criteria required to satisfy this hypothesis are put forth, and potential experimental approaches required are outlined. Such rigorous treatment of this issue will assist in maintaining the rapid pace of advance in this field.
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State-dependent release of acetylcholine in rat thalamus measured by in vivo microdialysis
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1994Co-Authors: Julie A. Williams, Hans C Fibiger, Jeff Comisarow, Jamie C. Day, Peter B ReinerAbstract:Mesopontine cholinergic neurons have long been thought to play a key role in behavioral state control. In particular, they have been implicated in the process of EEG desynchrony and in the generation of rapid eye movement (REM) sleep. However, the behavioral profile of identified Mesopontine cholinergic neurons has not been unequivocally demonstrated. In an attempt to address this issue, in vivo microdialysis was used to monitor acetylcholine (ACh) release across behavioral state in the rat thalamus, a major projection site of Mesopontine cholinergic neurons. Because REM periods in rats are of short duration, a method was developed to collect and accumulate sufficiently large samples from each of the individual states of wake, slow-wave sleep, and REM sleep to permit off-line analysis via (HPLC- ECD). Probe placement and the source of cholinergic innervation to the vicinity of the microdialysis probe were verified using retrograde tracing combined with ChAT immunohistochemistry. Finally, the sodium and calcium dependence of ACh measured in the thalamus were tested using TTX and calcium-free dialysates. The results showed that (1) extracellular ACh concentrations in the thalamus are high during both wake and REM sleep and significantly lower during slow-wave sleep, (2) the majority of cholinergic projections to the vicinity of the dialysis probes originate in the Mesopontine tegmentum, and (3) ACh release in the thalamus is due to sodium- and calcium-dependent mechanisms. In contrast to predictions of some previous hypotheses, these results demonstrate that Mesopontine cholinergic neurons are active during both wake and REM sleep.
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Noradrenaline hyperpolarizes identified rat Mesopontine cholinergic neurons in vitro
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1993Co-Authors: Julie A. Williams, Peter B ReinerAbstract:Inhibition of brainstem cholinergic neurons by noradrenergic neurons of the locus ceruleus has long been suggested as a key mechanism of behavioral state control. In particular, the commonly held view is that noradrenaline (NA) plays a permissive role in rapid eye movement (REM) sleep generation by disinhibiting brainstem cholinergic neurons. While this notion has been supported by numerous investigations, the inhibition of cholinergic neurons by NA has never been directly demonstrated. The purpose of this study was to investigate the effects of NA upon identified cholinergic neurons in the rat Mesopontine tegmentum. Using whole-cell patch-clamp recordings in slices, 175 cells were studied during bath application of 50 microM NA. Cholinergic neurons were positively identified by intracellular labeling with biocytin and subsequent staining with NADPH-diaphorase, a reliable marker for brainstem cholinergic neurons (Vincent et al., 1983). Successful intracellular labeling was obtained in 96 cells. Ninety-two percent (36 of 39) of cholinergic neurons hyperpolarized in response to NA, while noncholinergic cells (n = 57) exhibited mixed responses. Application of NA in a low-Ca2+, high-Mg2+ solution elicited the same hyperpolarizing effect as in normal solution, which indicated that the effect of NA on cholinergic neurons was direct. The noradrenergic hyperpolarization was mimicked by the alpha 2-adrenoceptor agonist UK- 14,304, and was blocked by the alpha 2-adrenoceptor antagonist idazoxan, which suggested an alpha 2-mediated response. Finally, voltage-clamp experiments revealed that NA activates the inwardly rectifying potassium current, IKG.(ABSTRACT TRUNCATED AT 250 WORDS)
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Membrane properties of Mesopontine cholinergic neurons studied with the whole-cell patch-clamp technique: implications for behavioral state control
Journal of Neurophysiology, 1992Co-Authors: Anita Kamondi, Julie A. Williams, B. Hutcheon, Peter B ReinerAbstract:1. The whole-cell patch-clamp technique was used to study the membrane properties of identified cholinergic and noncholinergic laterodorsal tegmental neurons in slices of rat brain maintained in vitro. 2. On the basis of their expression of the transient outward potassium current IA and the transient inward calcium current IT, three classes of neurons were observed: type I neurons exhibited a large IT; type II neurons exhibited a prominent IA; and type III neurons exhibited both IA and IT. 3. Combining intracellular deposition of biocytin with NADPH diaphorase histochemistry revealed that the vast majority of type III neurons were cholinergic, whereas only a minority of type I and type II neurons were cholinergic. Thus Mesopontine cholinergic neurons possess intrinsic ionic currents capable of inducing burst firing. 4. Delineation of the intrinsic membrane properties of identified Mesopontine cholinergic neurons, in concert with recent results regarding the responses of these neurons to neurotransmitter agents, has led us to present a unifying and mechanistic hypothesis of brain stem cholinergic function in the control of behavioral states.