Neurochemical afferents controlling the activity of serotonergic neurons in the dorsal raphe nucleus: microiontophoretic studies in the awake cat

Abstract

Serotonergic (5-HT) neurons of the brainstem dorsal raphe nucleus (DRN) have been implicated in a diversity of physiological and behavioral processes in vertebrates. However, despite extensive information about the intrinsic properties and the efferent projections of this neurochemical system, little information is available regarding the afferents that control its activity. This study investigated the neurotransmitters that regulate the activity of DRN-5-HT neurons under physiologically relevant conditions, by utilizing microiontophoresis in combination with single-unit recordings in the awake, head-restrained cat. This made it possible to examine the direct effects of neurotransmitters on DRN-5-HT neuronal activity, and, through the use of specific antagonists, to study the roles of these neurotransmitter inputs during physiological conditions that influence DRN-5-HT neuronal activity. The results indicate that (1) iontophoretic application of the GABA antagonist bicuculline reversed the typical suppression of neuronal activity seen during slow wave sleep, but had no effect on maintained activity during wakefulness. The suppression of neuronal activity during REM sleep was generally unaffected by application of bicuculline. This suggests a role for a GABAergic input to DRN-5-HT neurons in controlling some aspects of their state-dependent activity. (2) Iontophoretic application of the excitatory amino acid (EAA) antagonist kynurenic acid reduced the magnitude of the neuronal response evoked by phasic auditory stimuli, but had no effect on the spontaneous activity of these neurons, suggesting a role for an EAA input to the DRN in mediating the response to phasic sensory stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Midbrain Raphe Modulation of Nonphotic Circadian Clock Resetting and 5-HT Release in the Mammalian Suprachiasmatic Nucleus

“…These results are consistent with reports that GABA inhibits DRN neuronal activity (Gallager and Aghajanian, 1976;Levine and Jacobs, 1992) and mediates IPSPs in DRN serotonergic cells (Pan and Williams, 1989). Also, reduced DRN neuronal discharge during sleep is associated with increased GABA release, and this reduction is reversed by bicuculline (Levine and Jacobs, 1992;Nitz and Siegel, 1997;Gervasoni et al, 2000).…”

Preoptic Area Neurons and the Homeostatic Regulation of Rapid Eye Movement Sleep

“…These monoaminergic cells are active during waking, decrease activity during non-REM sleep, and become inactive during REM sleep (Heym et al, 1982;Fornal et al, 1985;Sakai, 1986;Reiner and McGeer, 1987;Yamuy et al, 1995Yamuy et al, , 1998Thakkar et al, 1998;Gervasoni et al, 2000). Evidence suggests that the quiescence of these cells during REM sleep is attributable to GABA-mediated inhibition (Levine and Jacobs, 1992;Wang et al, 1992;Siegel, 1996, 1997a,b;Gervasoni et al, 2000). Because both the MnPN and the vlPOA project to the DRN and LC (Zardetto-Smith and Johnson, 1995;Steininger et al, 2001;Lu et al, 2002) and they both contain populations of sleep-active GABAergic neurons, they may be a source of inhibition of monoaminergic systems at REM sleep onset.…”

Adult AMPA GLUA1 Receptor Subunit Loss in 5-HT Neurons Results in a Specific Anxiety-Phenotype with Evidence for Dysregulation of 5-HT Neuronal Activity

“…Thus, we hypothesize the enhanced AMPA response observed in 5-HT neurons lacking GLUA1 is mediated by receptors composed of the remaining subunits, which effectively substitute for GLUA1. During quiet wake and in animals under anesthesia, AMPA receptors on 5-HT neurons do not appear to be tonically activated (Levine and Jacobs, 1992). However, some evidence suggests that AMPA-mediated glutamatergic tone does drive 5-HT firing during the active dark phase (Tao and Auerbach, 2000).…”

“…The principal receptor for fast glutamate-mediated signal transmission is the AMPA receptor. In the raphe nuclei, it has been shown that activation of AMPA receptors on 5-HT neurons leads to increased firing in these neurons and increased 5-HT release (Gartside et al, 2007;Levine and Jacobs, 1992). Four subunits of the AMPA receptor, GLUA1-A4, contribute to the formation of different cell-typedependent heterotetrameric receptors (Dingledine et al, 1999).…”