Serotonergic Regulation of Membrane Potential in Developing Rat Prefrontal Cortex: Coordinated Expression of 5-Hydroxytryptamine (5-HT)1A, 5-HT2A, and 5-HT7Receptors

Béïque, Jean Claude; Campbell, Brian; Perring, Paul; Hamblin, Mark W.; Walker, Paul D.; Mladenovic, Ljiljana; Andrade, Rodrigo

doi:10.1523/jneurosci.5113-03.2004

Cited by 175 publications

(177 citation statements)

References 77 publications

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“…DOI (3 mM, 15 min; 5-100 min washout) had little or no effect on membrane and spike properties of layer V pyramidal neurons, consistent with previous slice work in older animals (Zhang, 2003;Beique et al, 2004). All neurons were tested within 3 min of achieving whole-cell configuration, N ¼ 9 neurons before DOI, resting potential: À69.971.5 mV, spike amplitude: 90.072.5 mV; input resistance: 86.179.5 MO; N ¼ 10 cells after DOI, resting potential: À69.170.9 mV; spike amplitude 90.772.8 mV; input resistance: 90.0713.6 MO.…”

Section: Effects Of a Hallucinogen On Electrophysiological Propertiessupporting

confidence: 87%

Hallucinogen-Induced UP States in the Brain Slice of Rat Prefrontal Cortex: Role of Glutamate Spillover and NR2B-NMDA Receptors

Lambe

Aghajanian

2005

Neuropsychopharmacol

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Psychedelic hallucinogens (eg LSD or DOI) induce disturbances of mood, perception, and cognition through stimulation of serotonin 5-HT 2A receptors. While these drugs are not proconvulsant, they have been shown by microdialysis to increase extracellular glutamate in the prefrontal cortex. Electrophysiological studies in the rat prefrontal slice have shown that both LSD and DOI enhance a prolonged, late wave of glutamate release onto layer V pyramidal neurons after an electrical stimulus. Here, we hypothesize that the network activity underlying this UP state involves glutamate spillover from excitatory synapses. To test this hypothesis, we raised the viscosity of the extracellular solution by adding the inert macromolecule dextran (B1 mM) that is known to retard glutamate overflow into the extrasynaptic space. Dextran suppressed the UP state or late excitatory postsynaptic current (EPSC), but neither the fast EPSC, the traditional polysynaptic EPSC, nor a synaptic form of 5-HT 2A -mediated transmission (serotonin-induced spontaneous EPSCs). Consistent with the previous work showing that extrasynaptic glutamate transmission in adult depends on NR2B-containing NMDA receptors, we found that NR2B-selective antagonists, ifenprodil and Ro25-6981, also suppressed the late EPSCs. The effect of psychedelic hallucinogens on UP states could be partially mimicked by inhibiting glutamate uptake but only after blocking inhibitory group II metabotropic glutamate receptors. This difference suggests that hallucinogens increase glutamate spillover in a phasic manner unlike glutamate uptake inhibitors. Increases in glutamate spillover have been suggested to recruit synapses not directly in the pathway activated by the electrical stimulus. Such recruitment could account for certain cognitive, affective, and sensory perturbations generated by psychedelic hallucinogens.

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Section: Effects Of a Hallucinogen On Electrophysiological Propertiessupporting

confidence: 87%

Hallucinogen-Induced UP States in the Brain Slice of Rat Prefrontal Cortex: Role of Glutamate Spillover and NR2B-NMDA Receptors

Lambe

Aghajanian

2005

Neuropsychopharmacol

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“…The agonist was used to induce dissociation between LFP and MUA activity. This dissociation is due to the fact that BP554 selectively hyperpolarizes pyramidal neurons in cortex through an increase in potassium conductivity that clamps the neuronal membrane close to this ion's reversal potential (13,17). Because of this pharmacological specificity and the narrow distribution of 5-HT1A receptors around the axon hillock of these neurons, the 5-HT1A agonist BP554 acts as a gatekeeper for the output of the neuronal network (MUA) (14,18).…”

Section: Discussionmentioning

confidence: 99%

“…BP554 is a centrally active 5-HT1A agonist whose primary function is to raise the spike threshold of pyramidal neurons by hyperpolarization (11). The hyperpolarization triggered by the 5-HT1A receptor is mostly driven by a potassium current, stabilizing the membrane of pyramidal neurons at a hyperpolarized level and reaching a spiking threshold only under a much heavier synaptic load (12,13). In the macaque cortex, the 5-HT1A receptors show a discrete localization on the initial segment of the axon hillock in layer-3 and layer-5 pyramidal neurons (14).…”

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confidence: 99%

The effect of a serotonin-induced dissociation between spiking and perisynaptic activity on BOLD functional MRI

Rauch

Rainer

Logothetis

2008

Proc. Natl. Acad. Sci. U.S.A.

141

101

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The relationship of the blood oxygen-level-dependent (BOLD) signal to its underlying neuronal activity is still poorly understood. Combined physiology and functional MRI experiments suggested that local field potential (LFP) is a better predictor of the BOLD signal than multiunit activity (MUA). To further explore this relationship, we simultaneously recorded BOLD and electrophysiological activity while inducing a dissociation of MUA from LFP activity with injections of the neuromodulator BP554 into the primary visual cortex of anesthetized monkeys. BP554 is a 5-HT1A agonist acting primarily on the membrane of efferent neurons by potassium-induced hyperpolarization. Its infusion in visual cortex reliably reduced MUA without affecting either LFP or BOLD activity. This finding suggests that the efferents of a neuronal network pose relatively little metabolic burden compared with the overall presynaptic and postsynaptic processing of incoming afferents. We discuss implications of this finding for the interpretation of BOLD activity.5-HT1A ͉ BP554 ͉ local field potentials ͉ multiunit activity

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“…Other in vivo and in vitro studies suggest that 5-HT 7 receptors can mediate the effects of 5-HT on hippocampus glucocorticoid receptor expression (Weaver et al, 2001;Laplante et al, 2002;Beique et al, 2004). Glucocorticoid has been tentatively associated with neurotoxicity, and considering the neurodevelopmental hypothesis of schizophrenia might have some role in this disease (Cotter and Pariante, 2002).…”

Section: Introductionmentioning

confidence: 99%

Positive Association of the Serotonin 5-HT7 Receptor Gene with Schizophrenia in a Japanese Population

Ikeda

Iwata

Kitajima

et al. 2005

Neuropsychopharmacol

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Several lines of evidence suggest that abnormalities in the serotonin system may be related to the pathophysiology of schizophrenia. The 5-HT 7 receptor is considered to be a possible schizophrenia-susceptibility factor, based on findings from binding, animal, postmortem, and genomewide linkage studies. In this study, we conducted linkage disequilibrium (LD) mapping of the human 5-HT 7 receptor gene (HTR7) and selected four 'haplotype-tagging (ht) SNPs'. Using these four htSNPs, we then conducted an LD case-control association analysis in 383 Japanese schizophrenia patients and 351 controls. Two htSNPs (SNP2 and SNP5) and haplotypes were found to be associated with schizophrenia. A promoter SNP (SNP2) was further assessed in a dual-luciferase reporter assay, but it was not found to have any functional relevance. Although we failed to find an actual susceptibility variant that could modify the function of HTR7, our results support the supposition that HTR7 is a susceptibility gene for schizophrenia in this ethnic group.

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Serotonergic Regulation of Membrane Potential in Developing Rat Prefrontal Cortex: Coordinated Expression of 5-Hydroxytryptamine (5-HT)_1A, 5-HT_2A, and 5-HT₇Receptors

Abstract: The developing prefrontal cortex receives a dense serotonergic innervation, yet little is known about the actions of serotonin

Cited by 175 publications

References 77 publications

Hallucinogen-Induced UP States in the Brain Slice of Rat Prefrontal Cortex: Role of Glutamate Spillover and NR2B-NMDA Receptors

Hallucinogen-Induced UP States in the Brain Slice of Rat Prefrontal Cortex: Role of Glutamate Spillover and NR2B-NMDA Receptors

The effect of a serotonin-induced dissociation between spiking and perisynaptic activity on BOLD functional MRI

Positive Association of the Serotonin 5-HT7 Receptor Gene with Schizophrenia in a Japanese Population

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