Inhibition of firing rate and changes in the firing pattern of nigral dopamine neurons by γ-hydroxybutyric acid (GHBA) are specifically induced by activation of GABAB receptors

1998 ◽  
Vol 357 (6) ◽  
pp. 611-619 ◽  
Author(s):  
S. Erhardt ◽  
Bengt Andersson ◽  
Hans Nissbrandt ◽  
Göran Engberg
Keyword(s):  
Firing Rate ◽  
Firing Pattern ◽  
Dopamine Neurons ◽  
Gabab Receptors ◽  
Hydroxybutyric Acid

scholarly journals Intrinsic Dynamics in Neuronal Networks. I. Theory

2000 ◽  
Vol 83 (2) ◽  
pp. 808-827 ◽  
Author(s):  
P. E. Latham ◽  
B. J. Richmond ◽  
P. G. Nelson ◽  
S. Nirenberg
Keyword(s):  
Firing Rate ◽  
Firing Pattern ◽  
Neuronal Networks ◽  
Network Connectivity ◽  
Excitatory Input ◽  
High Rate ◽  
Inhibitory Neurons ◽  
Inhibitory Input ◽  
Dynamic Interactions ◽  
Firing Patterns

Many networks in the mammalian nervous system remain active in the absence of stimuli. This activity falls into two main patterns: steady firing at low rates and rhythmic bursting. How are these firing patterns generated? Specifically, how do dynamic interactions between excitatory and inhibitory neurons produce these firing patterns, and how do networks switch from one firing pattern to the other? We investigated these questions theoretically by examining the intrinsic dynamics of large networks of neurons. Using both a semianalytic model based on mean firing rate dynamics and simulations with large neuronal networks, we found that the dynamics, and thus the firing patterns, are controlled largely by one parameter, the fraction of endogenously active cells. When no endogenously active cells are present, networks are either silent or fire at a high rate; as the number of endogenously active cells increases, there is a transition to bursting; and, with a further increase, there is a second transition to steady firing at a low rate. A secondary role is played by network connectivity, which determines whether activity occurs at a constant mean firing rate or oscillates around that mean. These conclusions require only conventional assumptions: excitatory input to a neuron increases its firing rate, inhibitory input decreases it, and neurons exhibit spike-frequency adaptation. These conclusions also lead to two experimentally testable predictions: 1) isolated networks that fire at low rates must contain endogenously active cells and 2) a reduction in the fraction of endogenously active cells in such networks must lead to bursting.

Central effects of 1,4-butanediol are mediated by GABAB receptors via its conversion into γ-hydroxybutyric acid

2002 ◽  
Vol 441 (3) ◽  
pp. 157-163 ◽  
Author(s):  
Mauro A.M Carai ◽  
Giancarlo Colombo ◽  
Roberta Reali ◽  
Salvatore Serra ◽  
Ignazia Mocci ◽  
...  
Keyword(s):  
Gabab Receptors ◽  
Hydroxybutyric Acid ◽  
Central Effects

CENTRALLY GENERATED RHYTHMIC ACTIVITY AND MODULATORY FUNCTION OF THE OVIDUCTAL DORSAL UNPAIRED MEDIAN (DUM) NEURONES IN TWO ORTHOPTERAN SPECIES (CALLIPTAMUS SP. AND DECTICUS ALBIFRONS)

1993 ◽  
Vol 174 (1) ◽  
pp. 123-138 ◽  
Author(s):  
E. Kalogianni ◽  
G. Theophilidis
Keyword(s):  
Firing Rate ◽  
Firing Pattern ◽  
Anterior Part ◽  
Motor Pattern ◽  
Egg Laying ◽  
Abdominal Ganglion ◽  
Muscle Fibres ◽  
Motor Neurones ◽  
Rhythmic Firing ◽  
Dorsal Unpaired Median

The rhythmic firing pattern of the putatively octopaminergic dorsal unpaired median (DUM) neurones supplying the oviductal system of female orthopterans, Calliptamus sp. and Decticus albifrons, was examined. Our data provide evidence that the oviductal DUM neurones in the seventh abdominal ganglion modulate the oviductal motor pattern, both peripherally and centrally, during the inhibition of egg-laying behaviour. In a minimally dissected animal, rhythmic activation of the oviductal DUM and motor neurones can be readily elicited by isolation of the seventh abdominal ganglion from the anterior part of the nerve cord. The bursting activity of the DUM neurones is temporally correlated with the oviductal motor rhythm. Both populations of oviductal neurones retain their rhythmic firing pattern after total isolation of the genital ganglia, indicating the presence of an oviductal central pattern generator. The effects of stimulation of oviductal DUM neurones on the oviductal motor activity were monitored by recording intracellularly from oviductal muscle fibres and extracellularly from motor axons. These effects consist of a reduction in the amplitude and frequency of excitatory postsynaptic potentials (EPSPs) in the muscle fibre and in the firing rate in oviductal motor neurones. We suggest that the change in EPSP amplitude results from peripheral release of octopamine by DUM neurones. The decreased firing rate of motor neurones, however, appears to be a central effect, possibly caused by central release of octopamine by DUM neurones.

Role of GABAB receptors in the sedative/hypnotic effect of γ-hydroxybutyric acid

2001 ◽  
Vol 428 (3) ◽  
pp. 315-321 ◽  
Author(s):  
Mauro A.M Carai ◽  
Giancarlo Colombo ◽  
Giuliana Brunetti ◽  
Samuele Melis ◽  
Salvatore Serra ◽  
...  
Keyword(s):  
Gabab Receptors ◽  
Hydroxybutyric Acid ◽  
Hypnotic Effect

Pharmacological Modulation of the Gating Properties of Small Conductance Ca2+-Activated K+ Channels Alters the Firing Pattern of Dopamine Neurons In Vivo

2010 ◽  
Vol 104 (3) ◽  
pp. 1726-1735 ◽  
Author(s):  
Kjartan F. Herrik ◽  
Palle Christophersen ◽  
Paul D. Shepard
Keyword(s):  
Firing Rate ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Pacemaker Activity ◽  
Sk Channels ◽  
Pharmacological Modulation ◽  
Sk Channel ◽  
Discharge Patterns ◽  
Small Conductance

Dopamine (DA) neurons are autonomous pacemakers that occasionally fire bursts of action potentials, discharge patterns thought to reflect tonic and phasic DA signaling, respectively. Pacemaker activity depends on the concerted and cyclic interplay between intrinsic ion channels with small conductance Ca2+-activated K+ (SK) channels playing an important role. Bursting activity is synaptically initiated but neither the transmitters nor the specific ion conductances involved have been definitively identified. Physiological and pharmacological regulation of SK channel Ca2+ sensitivity has recently been demonstrated and could represent a powerful means of modulating the expression of tonic/phasic signaling in DA neurons in vivo. To test this premise, we characterized the effects of intravenous administration of the novel positive and negative SK channel modulators NS309 and NS8593, respectively, on the spontaneous activity of substantia nigra pars compacta DA neurons in anesthetized C57BL/6 mice. NS309, dose-dependently decreased DA cell firing rate, increased the proportion of regular firing cells, and eventually stopped spontaneous firing. By contrast, systemic administration of the negative SK channel modulator NS8593 increased firing rate and shifted the pattern toward increased irregularity/bursting; an effect similar to local application of the pore blocking peptide apamin. The altered firing patterns resulting from inhibiting SK currents persisted independently of changes in firing rates induced by administration of DA autoreceptor agonists/antagonists. We conclude that pharmacological modulation of SK channel Ca2+-sensitivity represents a powerful mechanism for switching DA neuron firing activity between tonic and phasic signaling modalities in vivo.

scholarly journals Cause of parkinsonian symptoms: Firing rate, firing pattern or dynamic activity changes?

Basal Ganglia ◽  
2015 ◽  
Vol 5 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Atsushi Nambu ◽  
Yoshihisa Tachibana ◽  
Satomi Chiken
Keyword(s):  
Firing Rate ◽  
Firing Pattern ◽  
Dynamic Activity

scholarly journals Circuit Mechanisms of L-DOPA-Induced Dyskinesia (LID)

2021 ◽  
Vol 15 ◽  
Author(s):  
Kai Yang ◽  
Xinyue Zhao ◽  
Changcai Wang ◽  
Cheng Zeng ◽  
Yan Luo ◽  
...  
Keyword(s):  
Firing Rate ◽  
Firing Pattern ◽  
Theoretical Models ◽  
Brain Regions ◽  
Term Treatment ◽  
Ensemble Model ◽  
Rate Model ◽  
Multisystem Disease ◽  
Long Term Treatment

L-DOPA is the criterion standard of treatment for Parkinson disease. Although it alleviates some of the Parkinsonian symptoms, long-term treatment induces L-DOPA–induced dyskinesia (LID). Several theoretical models including the firing rate model, the firing pattern model, and the ensemble model are proposed to explain the mechanisms of LID. The “firing rate model” proposes that decreasing the mean firing rates of the output nuclei of basal ganglia (BG) including the globus pallidus internal segment and substantia nigra reticulata, along the BG pathways, induces dyskinesia. The “firing pattern model” claimed that abnormal firing pattern of a single unit activity and local field potentials may disturb the information processing in the BG, resulting in dyskinesia. The “ensemble model” described that dyskinesia symptoms might represent a distributed impairment involving many brain regions, but the number of activated neurons in the striatum correlated most strongly with dyskinesia severity. Extensive evidence for circuit mechanisms in driving LID symptoms has also been presented. LID is a multisystem disease that affects wide areas of the brain. Brain regions including the striatum, the pallidal–subthalamic network, the motor cortex, the thalamus, and the cerebellum are all involved in the pathophysiology of LID. In addition, although both amantadine and deep brain stimulation help reduce LID, these approaches have complications that limit their wide use, and a novel antidyskinetic drug is strongly needed; these require us to understand the circuit mechanism of LID more deeply.

Slow Oscillatory Firing: A Major Firing Pattern of Dopamine Neurons in the Ventral Tegmental Area

2005 ◽  
Vol 94 (5) ◽  
pp. 3516-3522 ◽  
Author(s):  
Wei-Xing Shi
Keyword(s):  
Ventral Tegmental Area ◽  
Single Unit ◽  
Firing Pattern ◽  
Receptor Activation ◽  
Dopamine Neurons ◽  
Interspike Intervals ◽  
Firing Activity ◽  
Unit Recording ◽  
Ventral Tegmental

Using spectral analysis and in vivo single-unit recording in rats, the present study revealed a pronounced slow oscillation (SO) in the firing activity of about half the dopamine (DA) neurons recorded in the ventral tegmental area. DA neurons in this group tended to fire repetitive spike clusters, making them appear to be rhythmic bursting cells. However, only some of these burst-like events met the traditional “80/160 ms” burst criteria entirely. The observation that the SO could be found in nonbursting DA cells, occurred at frequencies different from those of bursts, and persisted after bursts were digitally removed from spike trains further supports the suggestion that the SO is different from the traditionally defined bursting. Interspike intervals (ISIs) had been thought to be bimodally distributed in bursting DA neurons. This study found that some nonbursting DA cells also had a bimodal ISI distribution and a significant number of bursting cells did not. In the majority of cells where less than half the spikes occurred in bursts, a bimodal ISI distribution was highly predictive of the presence of the SO. Results further showed that the generation of the SO required forebrain inputs to DA neurons but not the adrenergic α1 receptor activation responsible for psychostimulant-induced increases in the SO. Taken together, these results suggest that the SO is distinct from the traditionally defined bursting and represents a major firing pattern of DA neurons in the ventral tegmental area.

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