Median and Dorsal Raphe Neurons Are Not Electrophysiologically Identical

Beck, Sheryl G.; Pan, Yu-Zhen; Akanwa, Adaure; Kirby, Lynn G.

doi:10.1152/jn.00744.2003

Cited by 148 publications

(159 citation statements)

References 36 publications

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“…Once the whole cell configuration was obtained, cell characteristics were recorded using current clamp techniques. The cellular characteristics were measured as previously described (Beck et al, 2004). Following the collection of cell characteristics, the pyramidal cell was returned to voltage clamp mode at À60 mV.…”

Section: Whole-cell Recording In Ca1 Pyramidal and Dorsal Raphe Neuronsmentioning

confidence: 99%

“…Brain slice immunohistochemistry for biocytin and tryptophan hydroxylase was conducted to determine whether the neurons recorded from the pet + / + mice contained 5-HT as previously described (Beck et al, 2004). Slices from the pet1 À/À mice were also processed to detect expression of the lacZ marker of 5-HT precursor neurons as previously described (Scott et al, 2005), but using chicken anti-b-galactosidase (1 : 1000, Abcam) and FITC-conjugated goat anti-chicken (1 : 250, Abcam) antibodies.…”

Section: Immunohistochemistrymentioning

confidence: 99%

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The Presynaptic Component of the Serotonergic System is Required for Clozapine's Efficacy

Yadav

Abbas

Farrell

et al. 2010

Neuropsychopharmacol

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Clozapine, by virtue of its absence of extrapyramidal side effects and greater efficacy, revolutionized the treatment of schizophrenia, although the mechanisms underlying this exceptional activity remain controversial. Combining an unbiased cheminformatics and physical screening approach, we evaluated clozapine's activity at 42350 distinct molecular targets. Clozapine, and the closely related atypical antipsychotic drug olanzapine, interacted potently with a unique spectrum of molecular targets. This distinct pattern, which was not shared with the typical antipsychotic drug haloperidol, suggested that the serotonergic neuronal system was a key determinant of clozapine's actions. To test this hypothesis, we used pet1 À/À mice, which are deficient in serotonergic presynaptic markers. We discovered that the antipsychotic-like properties of the atypical antipsychotic drugs clozapine and olanzapine were abolished in a pharmacological model that mimics NMDA-receptor hypofunction in pet1 À/À mice, whereas haloperidol's efficacy was unaffected. These results show that clozapine's ability to normalize NMDA-receptor hypofunction, which is characteristic of schizophrenia, depends on an intact presynaptic serotonergic neuronal system.

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Section: Whole-cell Recording In Ca1 Pyramidal and Dorsal Raphe Neuronsmentioning

confidence: 99%

Section: Immunohistochemistrymentioning

confidence: 99%

The Presynaptic Component of the Serotonergic System is Required for Clozapine's Efficacy

Yadav

Abbas

Farrell

et al. 2010

Neuropsychopharmacol

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“…Interestingly, previous studies have reported differences between the neuronal properties of the DRN and MRN. 31 It is tempting to speculate that the MRN neuronal population sampled in this study may have corresponded to rhombomere 2−3 derived neurons. The availability of mice carrying intersectionally tagged neurons from these cell populations should greatly facilitate further exploration of this issue.…”

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confidence: 86%

Serotonin Neuron Diversity in the Dorsal Raphe

Andrade

Haj‐Dahmane

2013

ACS Chem. Neurosci.

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The dorsal raphe nucleus contains one of the largest groups of serotonergic neurons in the mammalian brain and is the main site of origin of the serotonergic projection to the cerebral cortex. Early electrophysiological studies suggested that serotonergic neurons in this cell group formed a homogeneous cell class. More recent studies however have reported heterogeneity among the core anatomical and electrophysiological properties of these neurons, thus raising the possibility that serotonergic neurons of this cell group may form two or more distinct cell classes. In this Viewpoint, we review these findings and suggest ways to look at cellular heterogeneity among serotonergic neurons.

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“…7,8 Moreover, in vitro patch-clamp studies conducted in brain slices demonstrated a high degree of variability in the passive and active membrane properties of 5-HT neurons. 9,10 Finally, anatomical and electrophysiological studies showed that 5-HT1A receptors are not only expressed in 5-HT neurons, but also in other neuronal classes in the raphe nuclei. 10−12 Together these evidence call to re-evaluate the definition of serotonergic cell, and to determine which methods are most appropriate for their identification.…”

mentioning

confidence: 99%

“…11,16 In addition, electrophysiological studies where hyperpolarizing responses elicited by superfusion of a 5-HT1A agonist were assessed, found a considerable number of nonresponding identified serotonergic cells. 9,10,12,25 We hypothesized that while following the classic dogma to identify 5-HT neurons, many investigators have discarded data involving 5-HT1A-negative serotonergic neurons.…”

mentioning

confidence: 99%

A Subpopulation of Serotonergic Neurons That Do Not Express the 5-HT1A Autoreceptor

Kiyasova

Bonnavion

Scotto-Lomassese

et al. 2012

ACS Chem. Neurosci.

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5-HT neurons are topographically organized in the hindbrain, and have been implicated in the etiology and treatment of psychiatric diseases such as depression and anxiety. Early studies suggested that the raphe 5-HT neurons were a homogeneous population showing similar electrical properties, and feedback inhibition mediated by 5-HT1A autoreceptors. We utilized histochemistry techniques in ePet1-eGFP and 5-HT1A-iCre/ R26R mice to show that a subpopulation of 5-HT neurons do not express the somatodendritic 5-HT1A autoreceptor mRNA. In addition, we performed patch-clamp recordings followed by singlecell PCR in ePet1-eGFP mice. From 134 recorded 5-HT neurons located in the dorsal, lateral, and median raphe, we found lack of 5-HT1A mRNA expression in 22 cells, evenly distributed across raphe subfields. We compared the cellular characteristics of these neuronal types and found no difference in passive membrane properties and general excitability. However, when injected with large depolarizing current, 5-HT1A-negative neurons fired more action potentials, suggesting a lack of autoinhibitory action of local 5-HT release. Our results support the hypothesis that the 5-HT system is composed of subpopulations of serotonergic neurons with different capacity for adaptation.T he 5-hydroxytryptamine (5-HT, serotonin) neurotransmitter system has been strongly implicated in the etiology and treatment of psychiatric diseases such as depression and anxiety. 1,2 5-HT neurons are topographically organized in the hindbrain where distinct groups of neurons receive and send synaptic inputs from/to specific brain regions, suggesting that the neuronal activity of subpopulation of 5-HT neurons is under discrete spatiotemporal control. 3 Given the occurrence of neurochemically diverse neurons in the raphe nuclei, early studies proposed a series of features or "landmarks", common to all 5-HT neurons, that would help in the identification of putative 5-HT cells. 4−6 These included the regular firing of broad action potentials (clocklike activity) followed by a large afterhyperpolarization potential, high input resistance, and suppression of firing by 5-hydroxytryptamine receptor 1A (5-HT1A) agonists. 4−6 However, this dogma is progressively being questioned. Recent studies found that the electrophysiological characteristics of chemically identified 5-HT neurons in the raphe are more diverse than originally thought. Using juxtacellular labeling techniques, it was found that, besides the population of slow-firing clocklike cells, in vivo discharge of 5-HT neurons also includes subpopulations of fastfiring and bursting neurons. 7,8 Moreover, in vitro patch-clamp studies conducted in brain slices demonstrated a high degree of variability in the passive and active membrane properties of 5-HT neurons. 9,10 Finally, anatomical and electrophysiological studies showed that 5-HT1A receptors are not only expressed in 5-HT neurons, but also in other neuronal classes in the raphe nuclei. 10−12 Together these evidence call to re-evaluate the defi...

show abstract

Median and Dorsal Raphe Neurons Are Not Electrophysiologically Identical

Cited by 148 publications

References 36 publications

The Presynaptic Component of the Serotonergic System is Required for Clozapine's Efficacy

The Presynaptic Component of the Serotonergic System is Required for Clozapine's Efficacy

Serotonin Neuron Diversity in the Dorsal Raphe

A Subpopulation of Serotonergic Neurons That Do Not Express the 5-HT1A Autoreceptor

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