Electrophysiological and pharmacological characterization of serotonergic dorsal raphe neurons recorded extracellularly and intracellularly in rat brain slices

Vandermaelen, Cam P.; Aghajanian, George K.

doi:10.1016/0006-8993(83)90011-2

Cited by 484 publications

(302 citation statements)

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“…The few spontaneously active 5-HT neurons in vitro represent a subset of cells with tonic pacemaker properties (Mosko and Jacobs, 1976;Burlhis and Aghajanian, 1987). Serotonergic spontaneously active cells in this study all had "clocklike" firing patterns whose rates fell within the range reported previously for 5-HT DRN neurons in vivo and in vitro (0.5-2.5 Hz; Vandermaelen and Aghajanian, 1983). Nonserotonergic spontaneously active cells had a significantly higher firing rate such that the firing rate of 4/5 cells was out of this reported range.…”

Section: Discussionsupporting

confidence: 76%

“…A long spike duration of approximately 1.8 ms has also been reported to distinguish 5-HT neurons (Vandermaelen and Aghajanian, 1983), though this property was statistically indistinguishable between the two cell types. A large AHP, both in amplitude (10-20 mV) and duration (200-800 ms) has been noted for 5-HT neurons (Vandermaelen and Aghajanian, 1983), though the AHPs from both cell types were large, falling within these ranges. Our findings thus indicate that these membrane characteristics, though accurately descriptive of 5-HT-containing DRN neurons, should not be used as a means of distinguishing 5-HT from non-5-HT-containing cells.…”

Section: Discussionmentioning

confidence: 95%

“…Aghajanian and Vandermaelen (1982), using in vivo intracellular recording techniques followed by neurochemical identification of the recorded cell, found that 5-HTcontaining neurons have a slow, rhythmic firing pattern, a large afterhyperpolarization potential (AHP), gradual interspike depolarization, and a long duration action potential. Later studies using intracellular recording in brain slices examined the characteristics of putative serotonergic neurons in more detail (Vandermaelen and Aghajanian, 1983;Burlhis and Aghajanian, 1987). These cells are either silent or spontaneously active with a slow, regular firing pattern (0.5-2.5 Hz), a high input resistance (150-400 MΩ), and have a long duration action potential (approximately 1.8 ms) followed by a large, slow AHP (amplitude=10-20 mV, duration=200-800 ms).…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

“…Although 5-CT is a mixed 5-HT 1/7 agonist, the hyperpolarization response examined here has been shown to be mediated by the 5-HT 1A receptor (Williams et al, 1988;Corradetti et al, 1996). α 1 adrenergic receptors were stimulated by bath application of the selective agonist phenylephrine (PE, 3 μM; Vandermaelen and Aghajanian, 1983;Pan et al, 1994).…”

Section: Intracellular Sharp Electrode Recordingmentioning

confidence: 99%

“…5A To explore this phenomenon more fully, the adrenergic agonist PE was administered in the perfusion bath of silent cells. PE elicits firing in 5-HT cells by stimulating α 1 receptors, a major excitatory input to 5-HT DRN cells in vivo that is severed in the in vitro slice preparation (Vandermaelen and Aghajanian, 1983;Pan et al, 1994). PE (3 μM) elicited firing in both 5-HT (N=5) and non-5-HT cells (N=7).…”

mentioning

confidence: 99%

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Distinguishing characteristics of serotonin and non-serotonin-containing cells in the dorsal raphe nucleus: electrophysiological and immunohistochemical studies

et al. 2003

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The membrane properties and receptor-mediated responses of rat dorsal raphe nucleus neurons were measured using intracellular recording techniques in a slice preparation. After each experiment, the recorded neuron was filled with neurobiotin and immunohistochemically identified as 5-hydroxytryptamine (5-HT)-immunopositive or 5-HT-immunonegative. The cellular characteristics of all recorded neurons conformed to previously determined classic properties of serotonergic dorsal raphe nucleus neurons: slow, rhythmic activity in spontaneously active cells, broad action potential and large afterhyperpolarization potential. Two electrophysiological characteristics were identified that distinguished 5-HT from non-5-HT-containing cells in this study. In 5-HT-immunopositive cells, the initial phase of the afterhyperpolarization potential was gradual (tau=7.3±1.9) and in 5-HTimmunonegative cells it was abrupt (tau=1.8±0.6). In addition, 5-HT-immunopositive cells had a shorter membrane time constant (tau=21.4±4.4) than 5-HT-immunonegative cells (tau=33.5±4.2). Interestingly, almost all recorded neurons were hyperpolarized in response to stimulation of the inhibitory 5-HT 1A receptor. These results suggested that 5-HT 1A receptors are present on non-5-HT as well as 5-HT neurons. This was confirmed by immunohistochemistry showing that although the majority of 5-HT-immunopositive cells in the dorsal raphe nucleus were double-labeled for 5-HT 1A receptor-IR, a small but significant population of 5-HT-immunonegative cells expressed the 5-HT 1A receptor. These results underscore the heterogeneous nature of the dorsal raphe nucleus and highlight two membrane properties that may better distinguish 5-HT from non-5-HT cells than those typically reported in the literature. In addition, these results present electrophysiological and anatomical evidence for the presence of 5-HT 1A receptors on non-5-HT neurons in the dorsal raphe nucleus.Keywords 5-HT; 5-HT 1A receptor; intracellular; slice; rat The dorsal raphe nucleus (DRN) is generally considered a serotonergic nucleus because it is the largest source of 5-hydroxytryptamine (5-HT) terminals in the forebrain. However, substantial evidence points to the heterogeneous nature of the DRN. For example, the proportion of 5-HT-containing cells in the DRN is estimated to range from one to two thirds (Steinbusch et al., 1980;Descarries et al., 1982;Jacobs and Azmitia, 1992;Baumgarten and Grozdanovic, 1997). The remaining non-serotonergic cells contain a variety of other neurotransmitters and neuromodulators including dopamine, norepinephrine, glutamate, *Corresponding author: Tel: +1-215-590-0656; fax: +1-215-590-0109. kirbyl@email.chop.edu (L. G. Kirby). NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2010 March 5. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptGABA, enkephalin, substance P, neuropeptide Y, thyrotropin-releasing hormone, vasoactive intestinal polypeptide, cholecystokinin, gastrin and neurotensin (for review...

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 95%

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Section: Intracellular Sharp Electrode Recordingmentioning

confidence: 99%

mentioning

confidence: 99%

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Distinguishing characteristics of serotonin and non-serotonin-containing cells in the dorsal raphe nucleus: electrophysiological and immunohistochemical studies

et al. 2003

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Lower brainstem catecholamine afferents to the rat dorsal raphe nucleus

et al. 1996

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A large body of data suggests that the activation of alpha 1 receptors by a tonic noradrenergic input might be responsible for the tonic discharge of the serotonergic neurons of the dorsal raphe nucleus (DRN). To test this hypothesis, it was necessary to determine the origin of the noradrenergic and adrenergic innervation of these neurons. For this purpose, we combined small iontophoretic injections of the sensitive retrograde tracer cholera toxin b subunit (CTb) in the different subdivisions of the DRN with tyrosine hydroxylase immunohistochemistry. After CTb injections in the ventral or dorsal parts of the central DRN, a small number of double-labeled cells was observed in the locus coeruleus (A6 noradrenergic cell group), the A5 noradrenergic group, the dorsomedial medulla (C3 adrenergic cell group), and the lateral paragigantocellular nucleus (C1 adrenergic cell group). After CTb injections in the lateral wings or the dorsal part of the rostral DRN, a similar number of double-labeled cells was seen in C3. Slightly more double-labeled cells were seen in A6 and A5. In addition, a substantial to large number of double-labeled cells appeared in C1, the commissural part of the nucleus of the solitary tract (A2 noradrenergic cell group) and the caudoventrolateral medulla (A1 noradrenergic cell group). These results indicate that the noradrenergic and adrenergic inputs to the DRN arise from all the catecholaminergic cell groups of the lower brainstem except the A7 noradrenergic group. They further reveal the existence of a topographical organization of these afferents to the different subdivisions of the DRN.

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Fluoxetine-induced desensitization of somatodendritic 5-HT1A autoreceptors is independent of glucocorticoid(s)

Poul¹,

Laaris²,

Hamon³

et al. 1997

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Previous in vitro studies showed that glucocorticoid receptor activation (notably by corticosterone) could induce a functional desensitization of somatodendritic 5-HT1A autoreceptors in the dorsal raphe nucleus [Laaris et al. (1995) Neuropharmacology 34:1201-1210], similar to that due to in vivo subchronic treatment with a 5-HT reuptake inhibitor, such as fluoxetine, in rats. In the present study, we investigated whether a link might exist between these effects, i.e., whether glucocorticoid receptor activation could be responsible for the fluoxetine-induced desensitization of 5-HT1A autoreceptors. In vitro recording in the dorsal raphe nucleus of brain-stem slices showed that subchronic treatment with fluoxetine (5 mg/kg intraperitoneally (i.p.), daily for 3-7 days) significantly reduced the potency of the 5-HT1A receptor agonist ipsapirone to inhibit the firing rate of serotoninergic neurons. Parallel experiments in adrenalectomized and sham-operated rats indicated that subchronic fluoxetine treatment produced a similar shift to the right of the ipsapirone inhibition curve in both groups of animals. Furthermore, the subchronic blockade of glucocorticoid receptors by RU 38486 (25 mg/kg subcutaneously (s.c.), daily) in intact rats treated with fluoxetine (5 mg/kg i.p., daily for 3 days) did not affect the ability of the latter treatment to reduce the potency of ipsapirone to inhibit the firing of serotoninergic neurons. These data suggest that glucocorticoid receptors (and their possible activation by corticosterone) are not involved in the functional desensitization of somatodendritic 5-HT1A autoreceptors, which occurs during long-term treatment with a serotonin reuptake inhibitor such as fluoxetine.

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Electrophysiological and pharmacological characterization of serotonergic dorsal raphe neurons recorded extracellularly and intracellularly in rat brain slices

Cited by 484 publications

References 25 publications

Distinguishing characteristics of serotonin and non-serotonin-containing cells in the dorsal raphe nucleus: electrophysiological and immunohistochemical studies

Distinguishing characteristics of serotonin and non-serotonin-containing cells in the dorsal raphe nucleus: electrophysiological and immunohistochemical studies

Lower brainstem catecholamine afferents to the rat dorsal raphe nucleus

Fluoxetine-induced desensitization of somatodendritic 5-HT1A autoreceptors is independent of glucocorticoid(s)

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