Serotonergic and Nonserotonergic Dorsal Raphe Neurons Are Pharmacologically and Electrophysiologically Heterogeneous

2004 ◽  
Vol 92 (6) ◽  
pp. 3532-3537 ◽  
Author(s):  
Silvia Marinelli ◽  
Stephen A. Schnell ◽  
Stephen P. Hack ◽  
MacDonald J. Christie ◽  
Martin W. Wessendorf ◽  
...  
Keyword(s):  
Action Potential ◽  
Tryptophan Hydroxylase ◽  
Large Population ◽  
Receptor Activation ◽  
Dorsal Raphe ◽  
Inward Currents ◽  
Different Populations ◽  
The Brain ◽  
Dorsal Raphé

The dorsal raphe nucleus (DRN) projects serotonergic axons throughout the brain and is involved in a variety of physiological functions. However, it also includes a large population of cells that contain other neurotransmitters. To clarify the physiological and pharmacological differences between the serotonergic and nonserotonergic neurons of the DRN, their postsynaptic responses to 5-hydroxytryptamine (5-HT, serotonin) and to selective activation of 5-HT1A or 5-HT2A/C receptors and their action potential characteristics were determined using in vitro patch-clamp recordings. The slices containing these neurons were then immunostained for tryptophan hydroxylase (TPH), a marker of serotonergic neurons. It was found that subpopulations of both serotonergic and nonserotonergic neurons responded to 5-HT with outward (i.e., inhibitory) and inward (i.e., excitatory) currents, responded to both 5-HT1A and 5-HT2A/C receptor activation with outward and inward currents, respectively, and displayed overlapping action potential characteristics. These findings suggest that serotonergic and nonserotonergic neurons in the DRN are both heterogeneous with respect to their individual pharmacological and electrophysiological characteristics. The findings also suggest that the activity of the different populations of DRN neurons will display heterogeneous changes when the serotonergic tone in the DRN is altered by neurological disorders or by drug treatment.

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 Dorsal raphe serotonin neurotransmission is required for the expression of nursing behavior and for pup survival

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aude Muzerelle ◽  
Mariano Soiza-Reilly ◽  
Cornelia Hainer ◽  
Pierre-Louis Ruet ◽  
Klaus-Peter Lesch ◽  
...  
Keyword(s):  
Tryptophan Hydroxylase ◽  
Dorsal Raphe ◽  
Normal Mammary Gland ◽  
Knock Out ◽  
Maternal Experience ◽  
Pup Retrieval ◽  
Pup Survival ◽  
Gland Development ◽  
Severe Growth ◽  
Dorsal Raphé

AbstractProper maternal care is an essential factor of reproductive success in mammals, involving a repertoire of behaviors oriented toward the feeding and care of the offspring. Among the neurotransmitters involved in the initiation of these behaviors, serotonin (5-HT) seems to play an important role. Here we compared pup-oriented maternal behaviors in mice with constitutive 5-HT depletion, the tryptophan hydroxylase 2-knock-out (Tph2-KO) and the Pet1-KO mice. We report that the only common pup-oriented defect in these 2 hyposerotoninergic models is a defective nursing in parturient mice and altered nursing-like (crouching) behavior in virgin mice, while pup retrieval defects are only present in Tph2-KO. Despite a normal mammary gland development and milk production, the defect in appropriate nursing is responsible for severe growth retardation and early lethality of pups born to hyposerotonergic dams. This nursing defect is due to acute rather constitutive 5-HT depletion, as it is reproduced by adult knockdown of Tph2 in the dorsal raphe nucleus in mothers with a prior normal maternal experience. We conclude that 5-HT innervation from the dorsal raphe is required for both the initiation and maintenance of a normal nursing behavior. Our findings may be related to observations of reduced maternal/infant interactions in human depression.

scholarly journals Simultaneous CMOS-Based Imaging of Calcium Signaling of the Central Amygdala and the Dorsal Raphe Nucleus During Nociception in Freely Moving Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Romeo Rebusi ◽  
Joshua Phillipe Olorocisimo ◽  
Jeric Briones ◽  
Yasumi Ohta ◽  
Makito Haruta ◽  
...  
Keyword(s):  
Calcium Signaling ◽  
Dorsal Raphe Nucleus ◽  
Dorsal Raphe ◽  
Raphe Nucleus ◽  
Central Amygdala ◽  
Critical Areas ◽  
Freely Moving ◽  
Increased Activity ◽  
The Brain ◽  
Dorsal Raphé

Fluorescence imaging devices have been indispensable in elucidating the workings of the brain in living animals, including unrestrained, active ones. Various devices are available, each with their own strengths and weaknesses in terms of many factors. We have developed CMOS-based needle-type imaging devices that are small and lightweight enough to be doubly implanted in freely moving mice. The design also allowed angled implantations to avoid critical areas. We demonstrated the utility of the devices by using them on GCaMP6 mice in a formalin test experiment. Simultaneous implantations to the capsular-lateral central amygdala (CeLC) and dorsal raphe nucleus (DRN) were proven to be safe and did not hinder the execution of the study. Analysis of the collected calcium signaling data, supported by behavior data, showed increased activity in both regions as a result of pain stimulation. Thus, we have successfully demonstrated the various advantages of the device in its application in the pain experiment.

Activity-Related Calcium Dynamics in Motoneurons of the Nucleus Hypoglossus From Mouse

1999 ◽  
Vol 82 (6) ◽  
pp. 2936-2946 ◽  
Author(s):  
Mario B. Lips ◽  
Bernhard U. Keller
Keyword(s):  
Quantitative Analysis ◽  
Action Potential ◽  
Calcium Binding ◽  
Calcium Influx ◽  
Binding Capacity ◽  
Calcium Transients ◽  
Calcium Dynamics ◽  
The Brain

A quantitative analysis of activity-related calcium dynamics was performed in motoneurons of the nucleus hypoglossus in the brain stem slice preparation from mouse by simultaneous patch-clamp and microfluorometric calcium measurements. Motoneurons were analyzed under in vitro conditions that kept them in a functionally intact state represented by rhythmic, inspiratory-related bursts of excitatory postsynaptic currents and associated action potential discharges. Bursts of electrical activity were paralleled by somatic calcium transients resulting from calcium influx through voltage-activated calcium channels, where each action potential accounted for a calcium-mediated charge influx around 2 pC into the somatic compartment. Under in vivo conditions, rhythmic-respiratory activity in young mice occurred at frequencies up to 5 Hz, demonstrating the necessity for rapid calcium elevation and recovery in respiratory-related neurons. The quantitative analysis of hypoglossal calcium homeostasis identified an average extrusion rate, but an exceptionally low endogenous calcium binding capacity as cellular parameters accounting for rapid calcium signaling. Our results suggest that dynamics of somatic calcium transients 1) define an upper limit for the maximum frequency of respiratory-related burst discharges and 2) represent a potentially dangerous determinant of intracellular calcium profiles during pathophysiological and/or excitotoxic conditions.

GAT-1 and Reversible GABA Transport in Bergmann Glia in Slices

2002 ◽  
Vol 88 (3) ◽  
pp. 1407-1419 ◽  
Author(s):  
L. Barakat ◽  
A. Bordey
Keyword(s):  
Gaba Receptors ◽  
Receptor Activation ◽  
Bergmann Glia ◽  
Gaba Uptake ◽  
Induced Voltage ◽  
Nipecotic Acid ◽  
Gaba Transporters ◽  
Whole Cell Patch Clamp ◽  
Inward Currents

Although glial GABA uptake and release have been studied in vitro, GABA transporters (GATs) have not been characterized in glia in slices. Whole cell patch-clamp recordings were obtained from Bergmann glia in rat cerebellar slices to characterize carrier-mediated GABA influx and efflux. GABA induced inward currents at −70 mV that could be pharmacologically separated into GABAA receptor and GAT currents. In the presence of GABAA/B/C receptor blockers, mean GABA-induced currents measured −48 pA at −70 mV, were inwardly rectifying between −70 and +50 mV, were inhibited by external Na+ removal, and were diminished by reduction of external Cl−. Nontransportable blockers of GAT-1 (SKF89976-A and NNC-711) and a transportable blocker of all the GAT subtypes (nipecotic acid) reversibly reduced GABA-induced transport currents by 68 and 100%, respectively. A blocker of BGT-1 (betaine) had no effect. SKF89976-A and NNC-711 also suppressed baseline inward currents that likely result from tonic GAT activation by background GABA. The substrate agonists, nipecotic acid and β-alanine but not betaine, induced voltage- and Na+-dependent currents. With Na+ and GABA inside the patch pipette or intracellular GABA perfusion during the recording, SKF89976-A blocked baseline outward currents that activated at −60 mV and increased with more depolarized potentials. This carrier-mediated GABA efflux induced a local accumulation of extracellular GABA detected by GABAA receptor activation on the recorded cell. Overall, these results indicate that Bergmann glia express GAT-1 that are activated by ambient GABA. In addition, GAT-1 in glia can work in reverse and release sufficient GABA to activate nearby GABA receptors.

Sign in / Sign up

Export Citation Format

Share Document