scholarly journals Modelling spinal locomotor circuits for movements in developing zebrafish

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Yann Roussel ◽  
Stephanie F Gaudreau ◽  
Emily R Kacer ◽  
Mohini Sengupta ◽  
Tuan V Bui
Keyword(s):  
Spinal Cord ◽  
Synaptic Transmission ◽  
Motor Command ◽  
Rhythm Generation ◽  
Spinal Neurons ◽  
Firing Patterns ◽  
Locomotor Control ◽  
Musculoskeletal Models ◽  
Phase Relationships

Many spinal circuits dedicated to locomotor control have been identified in the developing zebrafish. How these circuits operate together to generate the various swimming movements during development remains to be clarified. In this study, we iteratively built models of developing zebrafish spinal circuits coupled to simplified musculoskeletal models that reproduce coiling and swimming movements. The neurons of the models were based upon morphologically or genetically identified populations in the developing zebrafish spinal cord. We simulated intact spinal circuits as well as circuits with silenced neurons or altered synaptic transmission to better understand the role of specific spinal neurons. Analysis of firing patterns and phase relationships helped identify possible mechanisms underlying the locomotor movements of developing zebrafish. Notably, our simulations demonstrated how the site and the operation of rhythm generation could transition between coiling and swimming. The simulations also underlined the importance of contralateral excitation to multiple tail beats. They allowed us to estimate the sensitivity of spinal locomotor networks to motor command amplitude, synaptic weights, length of ascending and descending axons, and firing behaviour. These models will serve as valuable tools to test and further understand the operation of spinal circuits for locomotion.

scholarly journals Modelling spinal locomotor circuits for movements in developing zebrafish

2021 ◽  
Author(s):  
Yann Roussel ◽  
Stephanie F. Gaudreau ◽  
Mohini Sengupta ◽  
Tuan V. Bui
Keyword(s):  
Motor Command ◽  
Experimental Results ◽  
Rhythm Generation ◽  
Synaptic Excitation ◽  
Locomotor Control ◽  
Musculoskeletal Models

ABSTRACTMany of the neural components of spinal circuits dedicated to locomotor control have been identified in the developing zebrafish. How these circuits operate together to generate the various swimming movements during development remains to be clarified. In this study, we iteratively construct models of zebrafish spinal circuits coupled to simplified musculoskeletal models that reproduce several developmental locomotor movements of zebrafish. The models replicate published experimental results examining the roles of synaptic excitation and inhibition and specific spinal populations to locomotor movements. Also, the models identify other possible mechanisms underlying the generation of locomotor movements by developing zebrafish. Notably, our modelling work demonstrates how the site of rhythm generation could transition between coiling and swimming, underlines the importance of contralateral excitation to multiple tail beats, and estimates the sensitivity of spinal locomotor networks to motor command amplitude, synaptic weights and firing behaviour.

Multiple Firing Patterns in Deep Dorsal Horn Neurons of the Spinal Cord: Computational Analysis of Mechanisms and Functional Implications

2010 ◽  
Vol 104 (4) ◽  
pp. 1978-1996 ◽  
Author(s):  
Yann Le Franc ◽  
Gwendal Le Masson
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Information Transfer ◽  
Network Effects ◽  
Neuronal Response ◽  
Sensory Information ◽  
Firing Patterns ◽  
Dorsal Horn Neurons ◽  
The Impact

Deep dorsal horn relay neurons (dDHNs) of the spinal cord are known to exhibit multiple firing patterns under the control of local metabotropic neuromodulation: tonic firing, plateau potential, and spontaneous oscillations. This work investigates the role of interactions between voltage-gated channels and the occurrence of different firing patterns and then correlates these two phenomena with their functional role in sensory information processing. We designed a conductance-based model using the NEURON software package, which successfully reproduced the classical features of plateau in dDHNs, including a wind-up of the neuronal response after repetitive stimulation. This modeling approach allowed us to systematically test the impact of conductance interactions on the firing patterns. We found that the expression of multiple firing patterns can be reproduced by changes in the balance between two currents (L-type calcium and potassium inward rectifier conductances). By investigating a possible generalization of the firing state switch, we found that the switch can also occur by varying the balance of any hyperpolarizing and depolarizing conductances. This result extends the control of the firing switch to neuromodulators or to network effects such as synaptic inhibition. We observed that the switch between the different firing patterns occurs as a continuous function in the model, revealing a particular intermediate state called the accelerating mode. To characterize the functional effect of a firing switch on information transfer, we used correlation analysis between a model of peripheral nociceptive afference and the dDHN model. The simulation results indicate that the accelerating mode was the optimal firing state for information transfer.

Activation of pharmacologically distinct metabotropic glutamate receptors depresses reticulospinal-evoked monosynaptic EPSPs in the lamprey spinal cord

1996 ◽  
Vol 76 (6) ◽  
pp. 3834-3841 ◽  
Author(s):  
P. Krieger ◽  
A. el Manira ◽  
S. Grillner
Keyword(s):  
Spinal Cord ◽  
Synaptic Transmission ◽  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Input Resistance ◽  
Spinal Neurons ◽  
Metabotropic Glutamate ◽  
Apparent Change ◽  
Glutamatergic Synaptic Transmission ◽  
Presynaptic Mechanisms

1. Different metabotropic glutamate receptors (mGluRs) can modulate synaptic transmission in different regions in the CNS, but their roles at individual synaptic connections have not been detailed. We used paired intracellular recordings from reticulospinal axons and their postsynaptic target neurons in the lamprey spinal cord to investigate the effects of mGluR activation on glutamatergic synaptic transmission. 2. The mGluR agonists (1S,3R)-1-aminocyclopentane-1,3-dicarboxyylic acid [(1S,3R)-ACPD] and L(+)-2-amino-4-phosphonobutyric acid (L-AP4) both reduced the amplitude of monosynaptic excitatory postsynaptic potentials (EPSPs) elicited by stimulation of single reticulospinal axons. The depression of monosynaptic unitary EPSPs occurred without any apparent change in the input resistance of postsynaptic neurons. Furthermore, the mGluR agonists did not affect the amplitude of (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced depolarizations. Taken together, these results thus suggest that (1S,3R)-ACPD and L-AP4 depress reticulospinal synaptic transmission via presynaptic mechanisms. 3. (2S,1'S,2'S)-2-(carboxycyclopropyl) glycine (L-CCG-I), which selectively activates group II mGluRs, also reduced the amplitude of reticulospinal-evoked EPSPs without any apparent change in the input resistance or membrane potential of the postsynaptic neuron. 4. The mGluR antagonist alpha-methyl-L-AP4 blocked the depression induced by L-AP4 but not that induced by (1S,3R)-ACPD. Furthermore, the effects of coapplication of (1S,3R)-ACPD and L-AP4 were additive, suggesting that they inhibit synaptic transmission by an action on pharmacologically distinct mGluRs. 5. These results provide evidence for the colocalization of at least two different subtypes of presynaptic mGluRs on a single reticulospinal axon in the lamprey. These presynaptic mGluRs could serve as glutamatergic autoreceptors limiting the extent of reticulospinal-mediated excitation of spinal neurons.

Differential effects of tetanus toxin on inhibitory and excitatory synaptic transmission in mammalian spinal cord neurons in culture: a presynaptic locus of action for tetanus toxin

1987 ◽  
Vol 57 (1) ◽  
pp. 121-131 ◽  
Author(s):  
G. K. Bergey ◽  
H. Bigalke ◽  
P. G. Nelson
Keyword(s):  
Spinal Cord ◽  
Synaptic Transmission ◽  
Tetanus Toxin ◽  
Excitatory Synaptic Transmission ◽  
Excitatory Postsynaptic Potential ◽  
Spinal Neurons ◽  
Spinal Cord Neurons ◽  
Excitatory Transmission ◽  
Quantal Size ◽  
Marked Diminution

Tetanus toxin reduces monosynaptic inhibitory and excitatory synaptic transmission in mouse spinal cord neurons in culture. Inhibitory transmission is preferentially reduced by the toxin; however, excitatory transmission is also ultimately reduced and blocked by the concentrations of toxin used in these studies. Recordings from monosynaptically connected cell pairs revealed a marked diminution in amplitude of evoked monosynaptic inhibitory postsynaptic potentials coincident with the onset of convulsant action at a time when evoked monosynaptic EPSPs were relatively unaffected. Increased polysynaptic excitation occurred as a result of diminished inhibition. This supports the reduction of inhibition as an important mechanism in the convulsant action of tetanus toxin. Quantal analysis of the late effects of tetanus toxin on the monosynaptic excitatory postsynaptic potential revealed a reduction in quantal number with no reduction in quantal size, thus demonstrating a presynaptic locus of action for the toxin on spinal neurons.

scholarly journals Pain Inhibits GRPR Neurons via GABAergic Signaling in the Spinal Cord

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Rita Bardoni ◽  
Kai-Feng Shen ◽  
Hui Li ◽  
Joseph Jeffry ◽  
Devin M. Barry ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neural Mechanisms ◽  
Projection Neurons ◽  
Spinal Neurons ◽  
Peptide Receptor ◽  
Gastrin Releasing Peptide ◽  
Spinal Mechanism ◽  
Itch Sensation ◽  
Neurokinin 1

Abstract It has been known that algogens and cooling could inhibit itch sensation; however, the underlying molecular and neural mechanisms remain poorly understood. Here, we show that the spinal neurons expressing gastrin releasing peptide receptor (GRPR) primarily comprise excitatory interneurons that receive direct and indirect inputs from C and Aδ fibers and form contacts with projection neurons expressing the neurokinin 1 receptor (NK1R). Importantly, we show that noxious or cooling agents inhibit the activity of GRPR neurons via GABAergic signaling. By contrast, capsaicin, which evokes a mix of itch and pain sensations, enhances both excitatory and inhibitory spontaneous synaptic transmission onto GRPR neurons. These data strengthen the role of GRPR neurons as a key circuit for itch transmission and illustrate a spinal mechanism whereby pain inhibits itch by suppressing the function of GRPR neurons.

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