scholarly journals Synaptic Control of Motoneuronal Excitability

2000 ◽  
Vol 80 (2) ◽  
pp. 767-852 ◽  
Author(s):  
Jens C. Rekling ◽  
Gregory D. Funk ◽  
Douglas A. Bayliss ◽  
Xiao-Wei Dong ◽  
Jack L. Feldman
Keyword(s):  
Motor Behavior ◽  
Membrane Properties ◽  
Metabotropic Receptors ◽  
Inward Current ◽  
Motor Commands ◽  
Second Messenger Systems ◽  
Presynaptic Release ◽  
Synaptic Control ◽  
The Brain ◽  
Release Processes

Movement, the fundamental component of behavior and the principal extrinsic action of the brain, is produced when skeletal muscles contract and relax in response to patterns of action potentials generated by motoneurons. The processes that determine the firing behavior of motoneurons are therefore important in understanding the transformation of neural activity to motor behavior. Here, we review recent studies on the control of motoneuronal excitability, focusing on synaptic and cellular properties. We first present a background description of motoneurons: their development, anatomical organization, and membrane properties, both passive and active. We then describe the general anatomical organization of synaptic input to motoneurons, followed by a description of the major transmitter systems that affect motoneuronal excitability, including ligands, receptor distribution, pre- and postsynaptic actions, signal transduction, and functional role. Glutamate is the main excitatory, and GABA and glycine are the main inhibitory transmitters acting through ionotropic receptors. These amino acids signal the principal motor commands from peripheral, spinal, and supraspinal structures. Amines, such as serotonin and norepinephrine, and neuropeptides, as well as the glutamate and GABA acting at metabotropic receptors, modulate motoneuronal excitability through pre- and postsynaptic actions. Acting principally via second messenger systems, their actions converge on common effectors, e.g., leak K+ current, cationic inward current, hyperpolarization-activated inward current, Ca2+channels, or presynaptic release processes. Together, these numerous inputs mediate and modify incoming motor commands, ultimately generating the coordinated firing patterns that underlie muscle contractions during motor behavior.

scholarly journals A Role for Xanthurenic Acid in the Control of Brain Dopaminergic Activity

2021 ◽  
Vol 22 (13) ◽  
pp. 6974
Author(s):  
Omar Taleb ◽  
Mohammed Maammar ◽  
Christian Klein ◽  
Michel Maitre ◽  
Ayikoe Guy Mensah-Nyagan
Keyword(s):  
Dopamine Release ◽  
Intraperitoneal Administration ◽  
Glutamate Transporter ◽  
Fold Increase ◽  
Xanthurenic Acid ◽  
Metabotropic Receptors ◽  
Parent Molecule ◽  
Dopaminergic Activity ◽  
The Brain

Xanthurenic acid (XA) is a metabolite of the kynurenine pathway (KP) synthetized in the brain from dietary or microbial tryptophan that crosses the blood-brain barrier through carrier-mediated transport. XA and kynurenic acid (KYNA) are two structurally related compounds of KP occurring at micromolar concentrations in the CNS and suspected to modulate some pathophysiological mechanisms of neuropsychiatric and/or neurodegenerative diseases. Particularly, various data including XA cerebral distribution (from 1 µM in olfactory bulbs and cerebellum to 0.1–0.4 µM in A9 and A10), its release, and interactions with G protein-dependent XA-receptor, glutamate transporter and metabotropic receptors, strongly support a signaling and/or neuromodulatory role for XA. However, while the parent molecule KYNA is considered as potentially involved in neuropsychiatric disorders because of its inhibitory action on dopamine release in the striatum, the effect of XA on brain dopaminergic activity remains unknown. Here, we demonstrate that acute local/microdialysis-infusions of XA dose-dependently stimulate dopamine release in the rat prefrontal cortex (four-fold increase in the presence of 20 µM XA). This stimulatory effect is blocked by XA-receptor antagonist NCS-486. Interestingly, our results show that the peripheral/intraperitoneal administration of XA, which has been proven to enhance intra-cerebral XA concentrations (about 200% increase after 50 mg/kg XA i.p), also induces a dose-dependent increase of dopamine release in the cortex and striatum. Furthermore, our in vivo electrophysiological studies reveal that the repeated/daily administrations of XA reduce by 43% the number of spontaneously firing dopaminergic neurons in the ventral tegmental area. In the substantia nigra, XA treatment does not change the number of firing neurons. Altogether, our results suggest that XA may contribute together with KYNA to generate a KYNA/XA ratio that may crucially determine the brain normal dopaminergic activity. Imbalance of this ratio may result in dopaminergic dysfunctions related to several brain disorders, including psychotic diseases and drug dependence.

scholarly journals A genetic manipulation of motor neuron excitability does not alter locomotor output in Drosophila larvae

2014 ◽  
Author(s):  
Erin C. McKiernan
Keyword(s):  
Motor Neuron ◽  
Motor Neurons ◽  
Motor Behavior ◽  
Genetic Manipulation ◽  
Motor Output ◽  
Membrane Properties ◽  
Neuron Excitability ◽  
Motor Neuron Excitability ◽  
The Face

Motor activity, like that producing locomotion, is generated by networks of neurons. At the last output level of these networks are the motor neurons, which send signals to the muscles, causing them to contract. Current research in motor control is focused on finding out how motor neurons contribute to shaping the timing of motor behaviors. Are motor neurons just passive relayers of the signals they receive? Or, do motor neurons shape the signals before passing them on to the muscles, thereby influencing the timing of the behavior? It is now well accepted that motor neurons have active, intrinsic membrane properties - there are ion channels in the cell membrane that allow motor neurons to respond to input in non-linear and diverse ways. However, few direct tests of the role of motor neuron intrinsic properties in shaping motor behavior have been carried out, and many questions remain about the role of specific ion channel genes in motor neuron function. In this study, two potassium channel transgenes were expressed in Drosophila larvae, causing motor neurons to fire at lower levels of current stimulation and at higher frequencies, thereby increasing excitability. Mosaic animals were created in which some identified motor neurons expressed the transgenes while others did not. Motor output underlying crawling was compared in muscles innervated by control and experimental neurons in the same animals. Counterintuitively, no effect of the transgenic manipulation on motor output was seen. Future experiments are outlined to determine how the larval nervous system produces normal motor output in the face of altered motor neuron excitability.

scholarly journals Transmitter Regulation of Plateau Properties in Turtle Motoneurons

1998 ◽  
Vol 79 (1) ◽  
pp. 45-50 ◽  
Author(s):  
Gytis Svirskis ◽  
Jørn Hounsgaard
Keyword(s):  
Membrane Potential ◽  
Metabotropic Glutamate Receptors ◽  
Input Resistance ◽  
Pattern Generation ◽  
Synaptic Activity ◽  
Membrane Properties ◽  
Resting Membrane Potential ◽  
Type I ◽  
Plateau Potentials ◽  
Inward Current

Svirskis, Gytis and Jørn Hounsgaard. Transmitter regulation of plateau properties in turtle motoneurons. J. Neurophysiol. 79: 45–50, 1998. In motoneurons, generation of plateau potentials is promoted by modulators that block potassium channels. In voltage-clamp experiments with triangular voltage ramp commands, we show that cis-(±)-1-aminocyclopentane-1,3-dicarboxylic acid ( cis-ACPD) and muscarine promote the generation of plateau potentials by increasing the dihydropyridine sensitive inward current, by increasing the input resistance, and by depolarizing the resting membrane potential. Type I metabotropic glutamate receptors (mGluR I) mediate the effects of cis-ACPD. Baclofen suppresses generation of plateau potentials by decreasing the dihydropyridine sensitive inward current, by decreasing the input resistance, and by hyperpolarizing the resting membrane potential. These results suggest that membrane properties of motoneurons are continuously modulated by synaptic activity in ways that may have profound effects on synaptic integration and pattern generation.

scholarly journals Output Units of Motor Behavior: An Experimental and Modeling Study

2000 ◽  
Vol 12 (1) ◽  
pp. 78-97 ◽  
Author(s):  
E. P. Loeb ◽  
S. F. Giszter ◽  
P. Saltiel and E. Bizzi ◽  
F. A. Mussa-Ivaldi
Keyword(s):  
Motor Control ◽  
Common Property ◽  
Motor Behavior ◽  
Muscle Synergies ◽  
Force Output ◽  
Time Dynamics ◽  
Motor Behaviors ◽  
Distinct Property ◽  
Small Set ◽  
The Brain

Cognitive approaches to motor control typically concern sequences of discrete actions without taking into account the stunning complexity of the geometry and dynamics of the muscles. This begs the question: Does the brain convert the intricate, continuous-time dynamics of the muscles into simpler discrete units of actions, and if so, how? One way for the brain to form discrete units of behavior from muscles is through the synergistic co-activation of muscles. While this possibility has long been known, the composition of potential muscle synergies has remained elusive. In this paper, we have focused on a method that allowed us to examine and compare the limb stabilization properties of all possible muscle combinations. We found that a small set (as few as 23 out of 65,536) of all possible combinations of 16 limb muscles are robust with respect to activation noise: these muscle combinations could stabilize the limb at predictable, restricted portions of the workspace in spite of broad variations in the force output of their component muscles. The locations at which the robust synergies stabilize the limb are not uniformly distributed throughout the leg's workspace, but rather, they cluster at four workspace areas. The simulated robust synergies are similar to the actual synergies we have previously found to be generated by activation of the spinal cord. Thus, we have developed a new analytical method that enabled us to select a few muscle synergies with interesting properties out of the set of possible muscle combinations. Beyond this, the identification of robustness as a common property of the synergies in simple motor behaviors will open the way to the study of dynamic stability, which is an important and distinct property of the vertebrate motor-control system.

Exogenous L-lactate promotes astrocyte plasticity but is not sufficient for enhancing striatal synaptogenesis or motor behavior in mice

2020 ◽  
Author(s):  
Adam J. Lundquist ◽  
Tyler J. Gallagher ◽  
Giselle M. Petzinger ◽  
Michael W. Jakowec
Keyword(s):  
Motor Behavior ◽  
Early Gene ◽  
Specific Gene ◽  
Motor Circuits ◽  
Specific Manner ◽  
Primary Astrocytes ◽  
Exercise Induced ◽  
The Brain

AbstractL-lactate is an energetic and signaling molecule that is key to the metabolic and neuroplastic connection between astrocytes and neurons and may be involved in exercise-induced neuroplasticity. This study sought to explore the role of L-lactate in astrocyte reactivity and neuroplasticity. Using in vitro cultures of primary astrocytes, we show L-lactate increased expression of plasticity-related genes, including neurotrophic factors, Bdnf, Gdnf, Cntf and the immediate early gene cFos. L-lactate’s promotion of neurotrophic factor expression may be mediated in part by the lactate receptor HCAR1 since application of the HCAR1 agonist 3,5-DHBA also increased expression of Bdnf in primary astrocytes. In vivo L-lactate administration to healthy mice caused a similar increase in the expression of plasticity-related genes as well as increased astrocyte morphological complexity in a region-specific manner, with increased astrocytic response found in the striatum but not the ectorhinal cortex, regions of the brain where increases in regional cerebral blood flow are increased or unaltered, respectively, with motor behavior. Additionally, L-lactate administration did not cause synaptogenesis or improve motor behavior based on the latency to fall on the accelerating rotarod, suggesting that L-lactate administration can initiate astrocyte-specific gene expression, but the activation of motor circuits is necessary to initiate striatal neuroplasticity. These results suggest that peripheral L-lactate is likely an important molecular component of exercise-induced neuroplasticity by acting in an astrocyte-specific manner to prime the brain for neuroplasticity.

Receiving the Synaptic Message

2017 ◽  
Author(s):  
Peggy Mason
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Adrenergic Receptors ◽  
Acetylcholine Receptors ◽  
G Protein Coupled Receptors ◽  
Metabotropic Receptors ◽  
Second Messenger Systems ◽  
Psychotropic Effects ◽  
G Protein Coupled ◽  
Ionotropic And Metabotropic Receptors

Ionotropic and metabotropic receptors differ in their speed of action, the variety of effects produced after ligand-binding, and in the number of types present in the nervous system. The participation of two ionotropic glutamate receptors in synaptic plasticity is thought to be the cellular basis of learning. The actions of acetylcholine on nicotinic acetylcholine receptors present at the neuromuscular junction are described. The pharmacological profile of the GABAA receptor, central to most neural functions, is introduced. The properties of metabotropic receptors that are coupled to G proteins, termed G protein-coupled receptors (GPCRs), are detailed. Three canonical second-messenger systems through which GPCRs act are briefly described. An introduction to clinical pharmacology focused on how drugs acting on muscarinic and adrenergic receptors produce peripheral and central psychotropic effects is provided. Finally, the role of connexins and gap junctions in myelination and hearing is introduced.

scholarly journals Hand size underestimation grows during childhood

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Lucilla Cardinali ◽  
Andrea Serino ◽  
Monica Gori
Keyword(s):  
Motor Behavior ◽  
Sensory Modality ◽  
The Body ◽  
Typically Developing ◽  
Cognitive Representations ◽  
Hand Size ◽  
Infancy And Childhood ◽  
Sensory Modalities ◽  
Sensory Maps ◽  
The Brain

Abstract Cortical body size representations are distorted in the adult, from low-level motor and sensory maps to higher levels multisensory and cognitive representations. Little is known about how such representations are built and evolve during infancy and childhood. Here we investigated how hand size is represented in typically developing children aged 6 to 10. Participants were asked to estimate their hand size using two different sensory modalities (visual or haptic). We found a distortion (underestimation) already present in the youngest children. Crucially, such distortion increases with age and regardless of the sensory modality used to access the representation. Finally, underestimation is specific for the body as no bias was found for object estimation. This study suggests that the brain does not keep up with the natural body growth. However, since motor behavior nor perception were impaired, the distortion seems functional and/or compensated for, for proper interaction with the external environment.

FMRFamide effects on membrane properties of heart cells isolated from the leech, Hirudo medicinalis

1992 ◽  
Vol 67 (2) ◽  
pp. 280-291 ◽  
Author(s):  
K. J. Thompson ◽  
R. L. Calabrese
Keyword(s):  
Isolated Heart ◽  
Muscle Cells ◽  
Membrane Properties ◽  
Slow Inward Current ◽  
Heart Cells ◽  
Linear Component ◽  
Inward Current ◽  
Isolated Heart Cells ◽  
Voltage Dependent ◽  
K Currents

1. The effects of the cardioactive peptide FMRFamide were tested on enzymatically dissociated muscle cells isolated from hearts of the leech. These cells were normally quiescent, with resting potentials near -60 mV. 2. Superfusion of FMRFamide induced a strong depolarization in isolated heart cells (e.g., greater than 40 mV with 10(-6) M FMRFamide). The depolarization was maintained in the continued presence of peptide and persisted long after its removal. Less frequently, FMRFamide superfusion elicited an episodic polarization rhythm. 3. The response of isolated heart cells to bath-applied FMRFamide showed a 1- to 2-min latency. The latency decreased with repeated applications of FMRFamide. 4. The FMRFamide response was diminished by Na+ replacement but persisted with Ca2+ channel blockade. 5. In voltage-clamped heart cells (-60 mv), superfusion of FMRFamide elicited a slow inward current with a transient and a sustained component. 6. Current-voltage (I-V) curves during FMRFamide superfusion in normal leech saline showed that FMRFamide also enhanced voltage-dependent outward currents activated at depolarized levels. 7. Under conditions in which K+ currents were substantially blocked, the FMRFamide-dependent I-V curve was net inward from -90 to +50 mV. A voltage-dependent component was blocked by Co2+ and a linear component by Na+ replacement. 8. We conclude that FMRFamide elicits a persistent inward current with a Na+ component and in addition modulates both voltage-dependent Ca2+ and K+ currents that may contribute to the normal myogenic activity of leech heart muscle cells.

Segment-specific effects of FMRFamide on membrane properties of heart interneurons in the leech

1995 ◽  
Vol 74 (4) ◽  
pp. 1485-1497 ◽  
Author(s):  
J. Schmidt ◽  
S. Gramoll ◽  
R. L. Calabrese
Keyword(s):  
Outward Current ◽  
Membrane Conductance ◽  
Membrane Properties ◽  
Inward Current ◽  
Specific Effects ◽  
Outward Currents ◽  
Voltage Dependent ◽  
Inward Currents ◽  
K Current ◽  
Conductance Increase

1. The effects of Phe-Met-Arg-Phe (FMRF)amide (10(-6) M) on membrane properties of heart interneurons in the third, fourth, and fifth segmental ganglia [HN(3), HN(4), and HN(5) cells, respectively] of the leech were studied using discontinuous current-clamp and single-electrode voltage-clamp techniques. FMRFamide was focally applied onto the soma of the cell under investigation. 2. Application of FMRFamide depolarized HN(3) and HN(4) cells by evoking an inward current. These responses were subject to pronounced desensitization. The inward currents evoked by application of FMRFamide were associated with an increase in membrane conductance and appeared to be voltage dependent. Currents were enhanced at more depolarized potentials. 3. The responsiveness of the HN(3) and HN(4) cells was not affected when the Ca2+ concentration in the bath saline was reduced from normal (1.8 mM) to 0.1 mM. The depolarizing response on application of FMRFamide was blocked when Co2+ was substituted for Ca2+. 4. HN(3) and HN(4) cells did not respond to FMRFamide application in Na(+)-free solution. Inward currents were largely reduced when bath saline with 30% of the normal Na+ concentration was used. When Li+ was substituted for Na+ in the saline, application of FMRFamide still evoked depolarizing responses in HN(3) and HN(4) cells. 5. We conclude that focal application of FMRFamide onto the somata of HN(3) and HN(4) cells evokes a voltage-dependent inward current, carried largely by Na+. 6. Focal application of FMRFamide onto somata of HN(5) cells hyperpolarized these cells by activating a voltage-dependent outward current. 7. HN(5) cells were loaded with Cl- until inhibitory postsynaptic potentials carried by Cl- reversed. Cl(-)-loaded cells still responded with a hyperpolarization when FMRFamide was applied onto their somata. Therefore the outward current evoked by FMRFamide appears to be mediated by a K+ conductance increase. 8. Application of FMRFamide onto the somata of HN(5) cells enhanced outward currents that were evoked by depolarizing voltage steps from a holding potential of -45 mV. 9. We conclude that the hyperpolarizing response of HN(5) cells to focal application of FMRFamide onto their somata is the result of an up-regulation of a voltage-dependent K+ current.

scholarly journals Differential effects of D-cycloserine and amantadine on motor behavior and D2/3 receptor binding in the nigrostriatal and mesolimbic system of the adult rat

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Susanne Nikolaus ◽  
Hans-Jörg Wittsack ◽  
Frithjof Wickrath ◽  
Anja Müller-Lutz ◽  
Hubertus Hautzel ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Motor Behavior ◽  
Small Animal ◽  
Exploratory Activity ◽  
Reference Region ◽  
Post Challenge ◽  
Adult Rats ◽  
Adult Rat ◽  
Agonist And Antagonist ◽  
The Brain

Abstract D-cycloserine (DCS) and amantadine (AMA) act as partial NMDA receptor (R) agonist and antagonist, respectively. In the present study, we compared the effects of DCS and AMA on dopamine D2/3R binding in the brain of adult rats in relation to motor behavior. D2/3R binding was determined with small animal SPECT in baseline and after challenge with DCS (20 mg/kg) or AMA (40 mg/kg) with [123I]IBZM as radioligand. Immediately post-challenge, motor/exploratory behavior was assessed for 30 min in an open field. The regional binding potentials (ratios of the specifically bound compartments to the cerebellar reference region) were computed in baseline and post-challenge. DCS increased D2/3R binding in nucleus accumbens, substantia nigra/ventral tegmental area, thalamus, frontal, motor and parietal cortex as well as anterodorsal and posterior hippocampus, whereas AMA decreased D2/3R binding in nucleus accumbens, caudateputamen and thalamus. After DCS, ambulation and head-shoulder motility were decreased, while sitting was increased compared to vehicle and AMA. Moreover, DCS increased rearing relative to AMA. The regional elevations of D2/3R binding after DCS reflect a reduction of available dopamine throughout the mesolimbocortical system. In contrast, the reductions of D2/3R binding after AMA indicate increased dopamine in nucleus accumbens, caudateputamen and thalamus. Findings imply that, after DCS, nigrostriatal and mesolimbic dopamine levels are directly related to motor/exploratory activity, whereas an inverse relationship may be inferred for AMA.

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