Activation of Presynaptic 5-Hydroxytryptamine 2A Receptors Facilitates Excitatory Synaptic Transmission via Protein Kinase C in the Dorsolateral Septal Nucleus

Hasuo, Hiroshi; Matsuoka, Toshimasa; Akasu, Takashi

doi:10.1523/jneurosci.22-17-07509.2002

Cited by 59 publications

(44 citation statements)

References 50 publications

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“…This later effect may result from the postsynaptic effect of 5HT on input resistance as analyzed in the mathematical model presented in this paper. However, the increase of EPSP amplitude in Dep MNs could also involve presynaptic mechanisms as was shown in rat dorsolateral septal nucleus via 5HT2A receptors (Hasuo et al, 2002).…”

Section: Effect Of 5ht On the Polysynaptic Excitatory Pathwaymentioning

confidence: 83%

Serotonin Enhances the Resistance Reflex of the Locomotor Network of the Crayfish through Multiple Modulatory Effects that Act Cooperatively

Bon-Jégo

Cattaert²,

Pearlstein³

2004

J. Neurosci.

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Serotonin (5HT) is an endogenous amine that modifies posture in crustacea. Here, we examined the mechanisms of action of 5HT on the resistance reflex in crayfish legs. This reflex, which counteracts movements imposed on a limb, is based on a negative feedback system formed by proprioceptors that sense joint angle movements and activate opposing motoneurons. We performed intracellular recordings from depressor motoneurons while repetitively stretching and releasing a leg joint proprioceptor in a resting in vitro preparation (i.e., a preparation that lacks spontaneous rhythmic activity). 5HT increased the amplitude of the depolarization during the release phase of the proprioceptor (corresponding to an upward movement of the leg) and the discharge frequency of the motoneurons. The 5HT-induced increase in the resistance reflex is caused, to a large extent, by polysynaptic pathways because it was very attenuated in the presence of high divalent cation solution. In addition to this activation of the polysynaptic pathways, 5HT also has postsynaptic effects that enhance the resistance reflex. 5HT causes a tonic depolarization, as well as an increase in the time constant and input resistance of motoneurons. We developed a simple mathematical model to describe the integrative properties of the motoneurons. The conclusion of this study is that the input frequency and the decay time constant of the EPSPs interact in such a way that small simultaneous changes in these parameters can cause a large effect on summation. Therefore, the conjunction of presynaptic and postsynaptic changes produces a strong cooperative effect on the resistance reflex response.

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Section: Effect Of 5ht On the Polysynaptic Excitatory Pathwaymentioning

confidence: 83%

Serotonin Enhances the Resistance Reflex of the Locomotor Network of the Crayfish through Multiple Modulatory Effects that Act Cooperatively

Bon-Jégo

Cattaert²,

Pearlstein³

2004

J. Neurosci.

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“…Serotonergic hyperpolarization at the axon initial segment via 5HT-1A receptors should increase the driving force for the depolarizing GABAergic input arriving from AACs (Khirug et al, 2008;Woodruff et al, 2009) supporting our results showing reliable disynaptic EPSPs due to spike triggering in pyramidal neurons by AACs in the presence of 5-HT. However, 5HT-2A receptor activation usually regarded as excitatory (Aghajanian and Marek, 1997) and implicated in a wide range of functions ranging from dendritic excitation in the neocortex (Aghajanian and Marek, 1997) to presynaptic facilitation (Hasuo et al, 2002) or depression (Best and Regehr, 2008) of glutamatergic transmission in subcortical areas also led to the suppression of glutamate-dependent feedforward network events. Moreover, activation of 5HT-2A receptors were found to suppress neuronal firing in the prefrontal cortex of monkeys while performing a working memory task (Williams et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Fluoxetine (Prozac) and Serotonin Act on Excitatory Synaptic Transmission to Suppress Single Layer 2/3 Pyramidal Neuron-Triggered Cell Assemblies in the Human Prefrontal Cortex

et al. 2012

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Selective serotonin reuptake inhibitors are the most widely prescribed drugs targeting the CNS with acute and chronic effects in cognitive, emotional and behavioral processes. This suggests that microcircuits of the human cerebral cortex are powerfully modulated by selective serotonin reuptake inhibitors, however, direct measurements of serotonergic regulation on human synaptic interactions are missing. Using multiple whole-cell patch-clamp recordings from neurons in acute cortical slices derived from nonpathological human samples of the prefrontal cortex, we show that neuronal assemblies triggered by single action potentials of individual neurons in the human cortex are suppressed by therapeutic doses of fluoxetine (Prozac). This effect is boosted and can be mimicked by physiological concentrations of serotonin through 5HT-2A and 5HT-1A receptors. Monosynaptic excitatory connections from pyramidal cells to interneurons were suppressed by application of serotonin leaving the monosynaptic output of GABAergic cells unaffected. Changes in failure rate, in paired-pulse ratio, and in the coefficient of variation of the amplitude of EPSPs suggest a presynaptic action of serotonin. In conclusion, activation of neuronal assemblies, which were suggested as building blocks of high order cognitive processes, are effectively downregulated by the acute action of selective serotonin reuptake inhibitors or serotonin at the site of pyramidal output in human microcircuits.

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“…By activation of 5-HT 3 receptors, instead, 5-HT stimulates the release of either glutamate [7,57,185] or GABA [90,96,179]. Also 5-HT 2 receptors were shown to stimulate GABA release [2] and to either increase [2,72,177] or reduce [118] glutamate release in distinct structures.…”

Section: Modes Of Interactionmentioning

confidence: 99%

“…On the other side, 5-HT 2A receptors stimulate glutamate release from fibers arising in the CA1 and CA3 regions and directed to dorsolateral septal nucleus [72].…”

Section: Modulation Of Glutamate Transmissionmentioning

confidence: 99%

Serotonin as a Modulator of Glutamate- and GABA-Mediated Neurotransmission: Implications in Physiological Functions and in Pathology

Ciranna

2006

272

170

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Abstract:The neurotransmitter serotonin (5-HT), widely distributed in the central nervous system (CNS), is involved in a large variety of physiological functions. In several brain regions 5-HT is diffusely released by volume transmission and behaves as a neuromodulator rather than as a "classical" neurotransmitter. In some cases 5-HT is co-localized in the same nerve terminal with other neurotransmitters and reciprocal interactions take place. This review will focus on the modulatory action of 5-HT on the effects of glutamate and -amino-butyric acid (GABA), which are the principal neurotransmitters mediating respectively excitatory and inhibitory signals in the CNS. Examples of interaction at preand/or post-synaptic levels will be illustrated, as well as the receptors involved and their mechanisms of action. Finally, the physiological meaning of neuromodulatory effects of 5-HT will be briefly discussed with respect to pathologies deriving from malfunctioning of serotonin system.

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Activation of Presynaptic 5-Hydroxytryptamine 2A Receptors Facilitates Excitatory Synaptic Transmission via Protein Kinase C in the Dorsolateral Septal Nucleus

Cited by 59 publications

References 50 publications

Serotonin Enhances the Resistance Reflex of the Locomotor Network of the Crayfish through Multiple Modulatory Effects that Act Cooperatively

Serotonin Enhances the Resistance Reflex of the Locomotor Network of the Crayfish through Multiple Modulatory Effects that Act Cooperatively

Fluoxetine (Prozac) and Serotonin Act on Excitatory Synaptic Transmission to Suppress Single Layer 2/3 Pyramidal Neuron-Triggered Cell Assemblies in the Human Prefrontal Cortex

Serotonin as a Modulator of Glutamate- and GABA-Mediated Neurotransmission: Implications in Physiological Functions and in Pathology

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