scholarly journals Dual Orexin Actions on Dorsal Raphe and Laterodorsal Tegmentum Neurons: Noisy Cation Current Activation and Selective Enhancement of Ca2+ Transients Mediated by L-Type Calcium Channels

2008 ◽  
Vol 100 (4) ◽  
pp. 2265-2281 ◽  
Author(s):  
K. A. Kohlmeier ◽  
S. Watanabe ◽  
C. J. Tyler ◽  
S. Burlet ◽  
C. S. Leonard
Keyword(s):  
Brain Slices ◽  
Cholinergic Neurons ◽  
Cell Types ◽  
Dorsal Raphe ◽  
Central Neurons ◽  
Cation Current ◽  
Current Activation ◽  
Reticular Activating System ◽  
Selective Enhancement ◽  
Dorsal Raphé

The hypocretin/orexins (Hcrt/Orxs) are hypothalamic neuropeptides that regulate stress, addiction, feeding, and arousal behaviors. They depolarize many types of central neurons and can increase [Ca2+]i in some, including those of the dorsal raphe (DR) and laterodorsal tegmental (LDT) nuclei—two structures likely to contribute to the behavioral actions of Hcrt/Orx. In this study, we used simultaneous whole cell and Ca2+-imaging methods in mouse brain slices to compare the Hcrt/Orx-activated current in DR and LDT neurons and to determine whether it contributes to the Ca2+ influx evoked by Hcrt/Orx. We found Hcrt/Orx activates a similar noisy cation current that reversed near 0 mV in both cell types. Contrary to our expectation, this current did not contribute to the somatic Ca2+ influx evoked by Hcrt/Orx. In contrast, Hcrt/Orx enhanced the Ca2+ transients produced by voltage steps (−60 to −30 mV) by ∼30% even in neurons lacking an inward current. This effect was abolished by nifedipine, augmented by Bay-K and abolished by bisindolylmaleimide I. Thus Hcrt/Orx has two independent actions: activation of noisy cation channels that generate depolarization and activation of a protein kinase C (PKC)-dependent enhancement of Ca2+ transients mediated by L-type Ca2+ channels. Immunocytochemistry verified that both these actions occurred in serotonergic and cholinergic neurons, indicating that Hcrt/Orx can function as a neuromodulator in these key neurons of the reticular activating system. Because regulation of Ca2+ transients mediated by L-channels is often linked to the control of transcriptional signaling, our findings imply that Hcrt/Orxs may also function in the regulation of long-term homeostatic or trophic processes.

Opposing Electrophysiological Actions of 5-HT on Noncholinergic and Cholinergic Neurons in the Rat Ventral Pallidum In Vitro

2004 ◽  
Vol 92 (1) ◽  
pp. 433-443 ◽  
Author(s):  
C. Peter Bengtson ◽  
David J. Lee ◽  
Peregrine B. Osborne
Keyword(s):  
Partial Agonist ◽  
Brain Slices ◽  
Cholinergic Neurons ◽  
Receptor Activation ◽  
Dorsal Raphe ◽  
Ventral Pallidum ◽  
Inward Current ◽  
Inward Currents ◽  
Dorsal Raphé

The ventral pallidum in rat is a basal forebrain structure that contains neurons that project in the limbic striatopallidal circuitry and magnocellular cholinergic corticopetal neurons. Because 5-hydroxytryptamine (5-HT) terminals on dorsal raphe projections form close appositions with these neurons, we made patch-clamp recordings in immature rat brain slices to determine whether they are modulated by postsynaptic 5-HT receptors. Inward currents were predominantly induced by 5-HT in noncholinergic neurons, which were distinguished from cholinergic neurons by immunohistochemical and electrophysiological criteria. The inward current induced by 5-HT was mimicked and occluded when adenylyl cyclase was stimulated with forskolin, and was almost abolished when h-currents in noncholinergic neurons were blocked with cesium. Consistent with 5-HT7 receptor activation of h-curents by cAMP in other brain regions, we found inward currents were mimicked by the mixed 5-HT1/5-HT7 agonists 5-methoxytryptamine, and by 5-carboxamidotryptamine (5-CT), which was more potent than 5-HT. In contrast, 5-HT1 preferring 8-OH-DPAT was a weak partial agonist, and the 5-HT1–selective antagonist pindolol had no effect. However, despite this profile, antagonists that bind at the 5-HT7 receptor only partly reduced the agonist inward current (SB-269970 and clozapine), or had no effect (mianserin and pimozide). We found in cholinergic neurons that 5-HT predominantly induced hyperpolarizing currents, which were carried by potassium channels, and were smaller than currents induced by 8-OH-DPAT and 5-CT. We conclude from this study that ascending 5-HT projections from the dorsal raphe could have direct and opposite effects on the activities of neurons within the limbic striatopallidal and cholinergic corticopetal circuitry in the ventral pallidum.

scholarly journals A Neural Correlate of Predicted and Actual Reward-Value Information in Monkey Pedunculopontine Tegmental and Dorsal Raphe Nucleus during Saccade Tasks

2011 ◽  
Vol 2011 ◽  
pp. 1-21 ◽  
Author(s):  
Ken-ichi Okada ◽  
Kae Nakamura ◽  
Yasushi Kobayashi
Keyword(s):  
Reinforcement Learning ◽  
Dopaminergic Neurons ◽  
Dorsal Raphe Nucleus ◽  
Cholinergic Neurons ◽  
Extracellular Recording ◽  
Movement Control ◽  
Dorsal Raphe ◽  
Raphe Nucleus ◽  
Pedunculopontine Tegmental Nucleus ◽  
Dorsal Raphé

Dopamine, acetylcholine, and serotonin, the main modulators of the central nervous system, have been proposed to play important roles in the execution of movement, control of several forms of attentional behavior, and reinforcement learning. While the response pattern of midbrain dopaminergic neurons and its specific role in reinforcement learning have been revealed, the role of the other neuromodulators remains rather elusive. Here, we review our recent studies using extracellular recording from neurons in the pedunculopontine tegmental nucleus, where many cholinergic neurons exist, and the dorsal raphe nucleus, where many serotonergic neurons exist, while monkeys performed eye movement tasks to obtain different reward values. The firing patterns of these neurons are often tonic throughout the task period, while dopaminergic neurons exhibited a phasic activity pattern to the task event. The different modulation patterns, together with the activity of dopaminergic neurons, reveal dynamic information processing between these different neuromodulator systems.

Hypocretin/Orexin Peptide Signaling in the Ascending Arousal System: Elevation of Intracellular Calcium in the Mouse Dorsal Raphe and Laterodorsal Tegmentum

2004 ◽  
Vol 92 (1) ◽  
pp. 221-235 ◽  
Author(s):  
Kristi A. Kohlmeier ◽  
Takafumi Inoue ◽  
Christopher S. Leonard
Keyword(s):  
Intracellular Calcium ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Brain Slices ◽  
Dorsal Raphe ◽  
No Production ◽  
Orexin Receptors ◽  
Laterodorsal Tegmentum ◽  
Dependent Processes ◽  
Dorsal Raphé

Dysfunction of the hypocretin/orexin (Hcrt/Orx) peptide system is closely linked to the sleep disorder narcolepsy, suggesting that it is also central to the normal regulation of sleep and wakefulness. Indeed, Hcrt/Orx peptides produce long-lasting excitation of arousal-related neurons, including those in the laterodorsal tegmentum (LDT) and the dorsal raphe (DR), although the mechanisms underlying these actions are not understood. Since Hcrt/Orx mobilizes intracellular calcium ([Ca2+]i) in cells transfected with orexin receptors and since receptor-mediated Ca2+ transients are ubiquitous signaling mechanisms, we investigated whether Hcrt/Orx regulates [Ca2+]i in the LDT and DR. Changes in [Ca2+]i were monitored by fluorescence changes of fura-2 AM loaded cells in young mouse brain slices. We found Hcrt/Orx (Orexin-A, 30-1,000 nM) evoked long-lasting increases in [Ca2+]i with differing temporal profiles ranging from spiking to smooth plateaus. A fragment of Hcrt/Orx (16-33) failed to evoke changes in [Ca2+]i and changes were not blocked by TTX or ionotropic glutamate receptor antagonists, suggesting they resulted from specific activation of postsynaptic orexin receptors. Unlike orexin receptor–transfected cells, Hcrt/Orx-responses were not attenuated by depletion of Ca2+ stores with cyclopiazonic acid (CPA; 3-30 μM), thapsigargin (3 μM), or ryanodine (20 μM), although store-depletion by either CPA or ryanodine blocked Ca2+ mobilization by the metabotropic glutamate receptor agonist (±)-1-aminocyclopentane- trans-1,3-dicarboxylic acid ( trans-ACPD; 30 μM). In contrast, Hcrt/Orx responses were strongly attenuated by lowering extracellular Ca2+ (∼20 μM) but were not inhibited by concentrations of KB-R7943 (10 μM) selective for blockade of sodium/calcium exchange. Nifedipine (10 μM), inhibited Hcrt/Orx responses but was more effective at abolishing spiking than plateau responses. Bay K 8644 (5-10 μM), an L-type calcium channel agonist, potentiated responses. Finally, responses were attenuated by inhibitors of protein kinase C (PKC) but not by inhibitors of adenylyl cyclase. Collectively, our findings indicate that Hcrt/Orx signaling in the reticular activating system involves elevation of [Ca2+]i by a PKC-involved influx of Ca2+ across the plasma membrane, in part, via L-type calcium channels. Thus the physiological release of Hcrt/Orx may help regulate Ca2+-dependent processes such as gene expression and NO production in the LDT and DR in relation with behavioral state. Accordingly, the loss of Hcrt/Orx signaling in narcolepsy would be expected to disrupt calcium-dependent processes in these and other target structures.

scholarly journals Target-specific modulation of the descending prefrontal cortex inputs to the dorsal raphe nucleus by cannabinoids

2016 ◽  
Vol 113 (19) ◽  
pp. 5429-5434 ◽  
Author(s):  
Sean D. Geddes ◽  
Saleha Assadzada ◽  
David Lemelin ◽  
Alexandra Sokolovski ◽  
Richard Bergeron ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Dorsal Raphe Nucleus ◽  
Cell Types ◽  
Dorsal Raphe ◽  
Raphe Nucleus ◽  
Wide Range ◽  
Stress Processing ◽  
Large Ensembles ◽  
Distributed Regulation ◽  
Dorsal Raphé

Serotonin (5-HT) neurons located in the raphe nuclei modulate a wide range of behaviors by means of an expansive innervation pattern. In turn, the raphe receives a vast array of synaptic inputs, and a remaining challenge lies in understanding how these individual inputs are organized, processed, and modulated in this nucleus to contribute ultimately to the core coding features of 5-HT neurons. The details of the long-range, top-down control exerted by the medial prefrontal cortex (mPFC) in the dorsal raphe nucleus (DRN) are of particular interest, in part, because of its purported role in stress processing and mood regulation. Here, we found that the mPFC provides a direct monosynaptic, glutamatergic drive to both DRN 5-HT and GABA neurons and that this architecture was conducive to a robust feed-forward inhibition. Remarkably, activation of cannabinoid (CB) receptors differentially modulated the mPFC inputs onto these cell types in the DRN, in effect regulating the synaptic excitatory/inhibitory balance governing the excitability of 5-HT neurons. Thus, the CB system dynamically reconfigures the processing features of the DRN, a mood-related circuit believed to provide a concerted and distributed regulation of the excitability of large ensembles of brain networks.

MDMA (3,4-methylenedioxymethamphetamine) inhibits the firing of dorsal raphe neurons in brain slices via release of serotonin

1989 ◽  
Vol 167 (3) ◽  
pp. 375-383 ◽  
Author(s):  
Jeffrey S. Sprouse ◽  
Charles W. Bradberry ◽  
Robert H. Roth ◽  
George K. Aghajanian
Keyword(s):  
Brain Slices ◽  
Dorsal Raphe ◽  
Dorsal Raphé ◽  
Raphe Neurons
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