5-Hydroxytryptamine increases spontaneous activity of subthalamic neurons in the rat

Flores, Gonzalo; Rosales, Manuel G.; Hernández, Salvador Villalpando; Sierra, Arturo; Aceves, Jorge

doi:10.1016/0304-3940(95)11597-p

Cited by 31 publications

(15 citation statements)

References 20 publications

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“…Interestingly, we also observed that the intrinsic properties of STN neurons are critical determinants of rebound bursting activity. Minute changes in the polarization of STN neurons were sufficient to alter the impact of similar patterns of IPSPs on STN neurons, suggesting that neuromodulators [e.g., acetylcholine (Féger et al 1979), serotonin (Flores et al 1995), and dopamine (Smith and Kieval 2000)] that are known to produce long-lasting changes in the polarization of neurons (reviewed by McCormick and Bal 1997) may be influential in determining the response of STN neurons to synaptic input from the GP. Finally, the observation that STN neurons are heterogeneous with respect to the duration of their rebound bursts implies that these neurons could participate in rhythmic burst activity of different frequencies.…”

Section: Functional Implicationsmentioning

confidence: 99%

Regulation of the Timing and Pattern of Action Potential Generation in Rat Subthalamic Neurons In Vitro by GABA-A IPSPs

Bevan

Magill

Hallworth

et al. 2002

Journal of Neurophysiology

177

170

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. The regulation of activity in the subthalamic nucleus (STN) by GABAergic inhibition from the reciprocally connected globus pallidus (GP) plays an important role in normal movement and disorders of movement. To determine the precise manner in which GABAergic synaptic input, acting at A-type receptors, influences the firing of STN neurons, we recorded the response of STN neurons to GABA-A inhibitory postsynaptic potentials (IPSPs) that were evoked by supramaximal electrical stimulation of the internal capsule using the perforatedpatch technique in slices at 37°C. The mean equilibrium potential of the GABA-A IPSP (EGABA-A IPSP) was Ϫ79.4 Ϯ 7.0 mV. Single IPSPs disrupted the spontaneous oscillation that underlies rhythmic single-spike firing in STN neurons. As the magnitude of IPSPs increased, the effectiveness of prolonging the interspike interval was related more strongly to the phase of the oscillation at which the IPSP was evoked. Thus the largest IPSPs tended to reset the oscillatory cycle, whereas the smallest IPSPs tended to produce relatively phaseindependent delays in firing. Multiple IPSPs were evoked at various frequencies and over different periods and their impact was studied on STN neurons held at different levels of polarization. Multiple IPSPs reduced and/or prevented action potential generation and/or produced sufficient hyperpolarization to activate a rebound depolarization, which generated a single spike or restored rhythmic spiking and/or generated a burst of activity. The pattern of IPSPs and the level of polarization of STN neurons were critical in determining the nature of the response. The duration of bursts varied from 20 ms to several hundred milliseconds, depending on the intrinsic rebound properties of the postsynaptic neuron. These data demonstrate that inhibitory input from the GP can produce a range of firing patterns in STN neurons, depending on the number and frequencies of IPSPs and the membrane properties and voltage of the postsynaptic neuron.

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Section: Functional Implicationsmentioning

confidence: 99%

Regulation of the Timing and Pattern of Action Potential Generation in Rat Subthalamic Neurons In Vitro by GABA-A IPSPs

Bevan

Magill

Hallworth

et al. 2002

Journal of Neurophysiology

177

170

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“…Electrophysiological investigation of serotonin in STN neurons is limited to only one extracellular recording study (Flores et al 1995), which reported an increase in firing by 5-HT. Our study was designed to analyze in detail the effect of 5-HT on firing properties of STN neurons and to determine underlying ionic mechanisms and the receptor subtypes involved.…”

Section: Introductionmentioning

confidence: 99%

Modulation of Spontaneous Firing in Rat Subthalamic Neurons by 5-HT Receptor Subtypes

Xiang

Wang²,

Kitai³

2005

Journal of Neurophysiology

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Xiang, Zixiu, Lie Wang, and Stephen T. Kitai. Modulation of spontaneous firing in rat subthalamic neurons by 5-HT receptor subtypes. J Neurophysiol 93: 1145-1157, 2005 doi:10.1152/jn.00561. 2004. The subthalamic nucleus (STN) is considered to be one of the driving forces in the basal ganglia circuit. The STN is innervated by serotonergic afferents from the raphe nucleus and expresses a variety of 5-HT receptor subtypes. We investigated the effects of 5-HT and 5-HT receptor subtype agonists and antagonists on the firing properties of STN neurons in rat brain slices. We used cell-attached, perforated-patch, and whole cell recording techniques to detect changes in firing frequency and pattern and electrical membrane properties. Due to the depolarization of membrane potential caused by reduced potassium conductance, 5-HT (10 M) increased the firing frequency of STN neurons without changing their firing pattern. Cadmium failed to occlude the effect of 5-HT on firing frequency. 5-HT had no effect on afterhyperpolarization current. These results indicated that the 5-HT action was not mediated by high-voltageactivated calcium channel currents and calcium-dependent potassium currents. 5-HT had no effect on hyperpolarization-activated cation current (I H ) amplitude and voltage-dependence of I H activation, suggesting that I H was not involved in 5-HT-induced excitation. The increased firing by 5-HT was mimicked by 5-HT 2/4 receptor agonist ␣-methyl-5-HT and was partially mimicked by 5-HT 2 receptor agonist DOI or 5-HT 4 receptor agonist cisapride. The 5-HT action was partially reversed by 5-HT 4 receptor antagonist SB 23597-190, 5-HT 2 receptor antagonist ketanserin, and 5-HT 2C receptor antagonist RS 102221. Our data indicate that 5-HT has significant ability to modulate membrane excitability in STN neurons; modulation is accomplished by decreasing potassium conductance by activating 5-HT 4 and 5-HT 2C receptors.

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“…Endogenous application of 5-HT in mouse and rat brain slices increased the firing frequency of subthalamic neurons (Flores et al, 1995;Stanford et al, 2005;Xiang et al, 2005).…”

Section: -Ht Modulation Of Stn Activitymentioning

confidence: 92%

“…The most frequent response to 5-HT seems to be an excitation of STN neurons (Flores et al, 1995;Stanford et al, 2005;Xiang et al, 2005;Shen et al, 2007). This effect is mediated by the activation of the 5-HT 2C and 5-HT 4 receptors being reversed by the combined use of selective antagonists for 5-HT 4 and 5-HT 2C receptors (Stanford et al, 2005;Xiang et al, 2005).…”

Section: -Ht Modulation Of Stn Activitymentioning

confidence: 99%

Serotonin modulation of the basal ganglia circuitry: therapeutic implication for Parkinson's disease and other motor disorders

Matteo

Pierucci

Esposito

et al. 2008

Progress in Brain Research

133

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Several recent studies have emphasized a crucial role for the interactions between serotonergic and dopaminergic systems in movement control and the pathophysiology of basal ganglia. These observations are supported by anatomical evidence demonstrating large serotonergic innervation of all the basal ganglia nuclei. In fact, serotonergic terminals have been reported to make synaptic contacts with both substantia nigra dopamine-containing neurons and their terminal areas such as the striatum, the globus pallidus and the subthalamus. These brain areas contain a high concentration of serotonin (5-HT), with the substantia nigra pars reticulata receiving the greatest input. In this chapter, the distribution of different 5-HT receptor subtypes in the basal ganglia nuclei will be described. Furthermore, evidence demonstrating the serotonergic control of basal ganglia activity will be reviewed and the contribution of the different 5-HT receptor subtypes examined. The new avenues that the increasing knowledge of 5-HT in motor control has opened for exploring the pathophysiology and pharmacology of Parkinson's disease and other movement disorders will be discussed. It is clear that these avenues will be fruitful, despite the disappointing results so far obtained by clinical studies with selective 5-HT ligands. Nevertheless, these studies have led to a great increase in the attention given to the neurotransmitters of the basal ganglia and their connections.

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5-Hydroxytryptamine increases spontaneous activity of subthalamic neurons in the rat

Cited by 31 publications

References 20 publications

Regulation of the Timing and Pattern of Action Potential Generation in Rat Subthalamic Neurons In Vitro by GABA-A IPSPs

Regulation of the Timing and Pattern of Action Potential Generation in Rat Subthalamic Neurons In Vitro by GABA-A IPSPs

Modulation of Spontaneous Firing in Rat Subthalamic Neurons by 5-HT Receptor Subtypes

Serotonin modulation of the basal ganglia circuitry: therapeutic implication for Parkinson's disease and other motor disorders

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