Regulation of motor neuron dendrite growth by NMDA receptor activation

Development ◽  
1994 ◽  
Vol 120 (11) ◽  
pp. 3063-3071 ◽  
Author(s):  
R.G. Kalb
Keyword(s):  
Nmda Receptor ◽  
Motor Neuron ◽  
Cell Body ◽  
Motor Neurons ◽  
Receptor Activation ◽  
Dendrite Growth ◽  
Postnatal Life ◽  
Receptor Antagonism ◽  
Neuron Cell Body ◽  
Early Postnatal Life

Spinal motor neurons undergo great changes in morphology, electrophysiology and molecular composition during development. Some of this maturation occurs postnatally when limbs are employed for locomotion, suggesting that neuronal activity may influence motor neuron development. To identify features of motor neurons that might be regulated by activity we first examined the structural development of the rat motor neuron cell body and dendritic tree labeled with cholera toxin-conjugated horseradish peroxidase. The motor neuron cell body and dendrites in the radial and rostrocaudal axes grew progressively over the first month of life. In contrast, the growth of the dendritic arbor/cell and number of dendritic branches was biphasic with overabundant growth followed by regression until the adult pattern was achieved. We next examined the influence of neurotransmission on the development of these motor neuron features. We found that antagonism of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor inhibited cell body growth and dendritic branching in early postnatal life but had no effect on the maximal extent of dendrite growth in the radial and rostrocaudal axes. The effects of NMDA receptor antagonism on motor neurons and their dendrites was temporally restricted; all of our anatomic measures of dendrite structure were resistant to NMDA receptor antagonism in adults. These results suggest that the establishment of mature motor neuron dendritic architecture results in part from dendrite growth in response to afferent input during a sensitive period in early postnatal life.

scholarly journals T-Box transcription factor Tbx20 regulates a genetic program for cranial motor neuron cell body migration

Development ◽  
2006 ◽  
Vol 133 (24) ◽  
pp. 4945-4955 ◽  
Author(s):  
M.-R. Song ◽  
R. Shirasaki ◽  
C.-L. Cai ◽  
E. C. Ruiz ◽  
S. M. Evans ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Motor Neuron ◽  
Cell Body ◽  
Genetic Program ◽  
T Box ◽  
Neuron Cell Body

Monosynaptic activation of different portions of the motor neuron membrane

1960 ◽  
Vol 198 (4) ◽  
pp. 693-703 ◽  
Author(s):  
Ettore Fadiga ◽  
John M. Brookhart
Keyword(s):  
Motor Neuron ◽  
Cell Body ◽  
Motor Neurons ◽  
Dorsal Root ◽  
Time Course ◽  
Intracellular Recordings ◽  
Neuron Membrane ◽  
Lateral Column ◽  
Root Stimulation

Using isolated frog spinal cords, treated with pentobarbital to silence internuncial discharge, intracellular recordings from motor neurons reveal differences in dendritically initiated EPSP evoked by dorsal root stimulation and somatically initiated EPSP evoked by lateral column stimulation. Under these conditions, dorsal root EPSP never reached motor neuron threshold whereas threshold was easily reached by lateral column EPSP. EPSP's initiated by dorsal root volleys were slower in their time course and smaller in their amplitude than those initiated by lateral column volleys. EPSP's initiated by lateral column volleys reduced the amplitude of antidromic spikes, while those produced by dorsal root stimulation did not. Lateral column induced EPSP was also capable of reducing the amplitude of orthodromic spikes. Some observations on duration of transmitter action are reported. It is concluded that dendritic excitation following a dorsal root volley influences the level of polarization of the cell body by electrotonic propagation of the resulting EPSP.

scholarly journals Ligand-independent activation of the P2X7 receptor by Hsp90 inhibition stimulates motor neuron apoptosis

2019 ◽  
Vol 244 (11) ◽  
pp. 901-914
Author(s):  
Amy L Strayer ◽  
Cassandra N Dennys-Rivers ◽  
Karina C Ricart ◽  
Narae Bae ◽  
Joseph S Beckman ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Motor Neurons ◽  
P2x7 Receptor ◽  
Receptor Activation ◽  
Neuron Death ◽  
Hsp90 Inhibition ◽  
Highly Sensitive ◽  
Motor Neuron Death ◽  
Lateral Sclerosis ◽  
Neuron Apoptosis

Activation of the extracellular ATP ionotropic receptor P2X7 stimulates motor neuron apoptosis, whereas its inhibition in cell and animal models of amyotrophic lateral sclerosis can be protective. These observations suggest that P2X7 receptor activation is relevant to motor neuron disease and that it could be targeted for therapeutic development. Heat shock protein 90 (Hsp90) is an integral regulatory component of the P2X7 receptor complex, antagonizing ligand-induced receptor activation. Here, we show that the repressive activity of Hsp90 on P2X7 receptor activation in primary motor neurons is highly sensitive to inhibition. Primary motor neurons in culture are 100-fold more sensitive to Hsp90 inhibition by geldanamycin than other neuronal populations. Pharmacological inhibition and down-regulation of the P2X7 receptor prevented motor neuron apoptosis triggered by Hsp90 inhibition, which occurred in the absence of extracellular ATP. These observations suggest that inhibition of a seemingly motor neuron specific pool of Hsp90 leads to ligand independent activation of P2X7 receptor and motor neuron death. Downstream of Hsp90 inhibition, P2X7 receptor activated the phosphatase and tensin homolog (TPEN), which in turn suppressed the pro-survival phosphatidyl inositol 3 kinase (PI3K)/Akt pathway, leading to Fas-dependent motor neuron apoptosis. Conditions altering the interaction between P2X7 receptor and Hsp90, such as recruitment of Hsp90 to other subcellular compartments under stress conditions, or nitration following oxidative stress can induce motor neuron death. These findings may have broad implications in neurodegenerative disorders, including amyotrophic lateral sclerosis, in which activation of P2X7 receptor may be involved in both autonomous and non-autonomous motor neurons death. Impact statement Here we show that a motor neuron specific pool of Hsp90 that is highly sensitive to geldanamycin inhibition represses ligand-independent activation of P2X7 receptor and is critical to motor neuron survival. Activation of P2X7 receptor by Hsp90 inhibition triggers motor neuron apoptosis through the activation of PTEN, which in turn inhibits the PI3 kinase/Akt survival pathway. Thus, inhibition of Hsp90 for therapeutic applications may have the unexpected negative consequence of decreasing the activity of trophic pathways in motor neurons. The inhibition of Hsp90 as a therapeutic approach may require the identification of the Hsp90 complexes involved in pathogenic processes and the development of inhibitors selective for these complexes.

scholarly journals Impulsive behaviour induced by both NMDA receptor antagonism and GABAA receptor activation in rat ventromedial prefrontal cortex

2011 ◽  
Vol 219 (2) ◽  
pp. 401-410 ◽  
Author(s):  
Emily R. Murphy ◽  
Anushka B. P. Fernando ◽  
Gonzalo P. Urcelay ◽  
Emma S. J. Robinson ◽  
Adam C. Mar ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nmda Receptor ◽  
Gabaa Receptor ◽  
Receptor Activation ◽  
Ventromedial Prefrontal Cortex ◽  
Receptor Antagonism ◽  
Impulsive Behaviour

Normal and abnormal development of an identified leech motor neuron

Development ◽  
1984 ◽  
Vol 79 (1) ◽  
pp. 125-137
Author(s):  
John Y. Kuwada
Keyword(s):  
Motor Neuron ◽  
Cell Body ◽  
Motor Neurons ◽  
Growth Cone ◽  
Abnormal Development ◽  
Lateral Part ◽  
Posterior Root ◽  
Large Size ◽  
Neuron Growth ◽  
Longitudinal Muscles

In embryonic and mature leeches, the identified L motor neuron, which innervates the longitudinal muscles of the contralateral half body segment, can be identified by the location and relatively large size of its cell body. Here the morphological and physiological development of the L motor neuron has been investigated by intracellular recording and dye-filling techniques in normal and abnormal embryonic leeches. Normally the L motor neuron growth cone projects from the cell body at about the same time as from many other neurons located in the lateral part of the ganglion, including the P mechanosensory neurons. The L motor axon, like many other leech axons, projects directly into the appropriate pathway. The L motor neuron does not initially extend an excessive number of axons followed by elimination of the inappropriate ones. Its growth cone is tapered and relatively free of filopodia and grows out of the ganglion in the contralateral posterior nerve behind the growth cone of the primary peripheral axon of the dorsal P mechanosensory cell, which is one of the earliest axons in the posterior root. Occasionally the bilateral halves of the germinal plate fail to fuse resulting in an embryo with separated but intact half ganglia, body wall, and skin. In such embryos the L motor neuron axons cannot grow out the contralateral posterior nerve since it is not available. Instead they grow out a variety of ipsilateral nerves and/or connective tracts. The P mechanosensory cells, which normally grow out of the ganglion in specific ipsilateral nerves, extend their axons along their normal pathways. In these abnormal embryos the L motor neurons did not preferentially grow into the ipsilateral posterior nerve, normally the pathway taken by the bilateral homologue and the nerve most similar to the L motor neuron's normal pathway. The failure of these L neurons to either consistently choose or avoid the ipsilateral posterior root suggests that the bilateral homologues ignore one another's pathfinding cues or that such cues are missing or changed in these embryos. The axons of the P neurons, however, appear to require no cues or interactions with contralateral structures or cells for normal development.

scholarly journals Neuromodulatory selection of motor neuron recruitment patterns in a visuomotor behavior increases speed

2019 ◽  
Author(s):  
Urvashi Jha ◽  
Vatsala Thirumalai
Keyword(s):  
Motor Neuron ◽  
Motor Neurons ◽  
Prey Capture ◽  
Receptor Activation ◽  
Motor Drive ◽  
List Type ◽  
Optomotor Response ◽  
Visuomotor Behavior ◽  
Larval Zebrafish ◽  
Selection Of

SummaryAnimals generate locomotion at different speeds to suit their behavioral needs. Spinal circuits generate locomotion at these varying speeds by sequential activation of different spinal interneurons and motor neurons. Larval zebrafish can generate slow swims for prey capture and exploration by activation of secondary motor neurons and much faster and vigorous swims during escapes and struggles via the additional activation of primary motor neurons. Neuromodulators are known to alter motor output of spinal circuits yet their precise role in speed regulation is not understood well. Here, in the context of optomotor response (OMR), an innate, evoked locomotor behavior, we show that dopamine (DA) provides an additional layer to regulation of swim speed in larval zebrafish. Activation of D1-like receptors increases swim speed during OMR in free-swimming larvae. By analysing tail bend kinematics in head-restrained larvae, we show that the increase in speed is actuated by larger tail bends. Whole cell patch clamp recordings from motor neurons reveal that during OMR, typically only secondary motor neurons are active while primary motor neurons are quiescent. Activation of D1-like receptors increases motor drive from secondary motor neurons by decreasing spike threshold and latency. In addition, D1-like receptor activation enhances excitability and recruits quiescent primary motor neurons. Our findings provide an example of neuromodulatory reconfiguration of spinal motor neuron speed modules such that members are selectively recruited and motor drive is increased to effect changes in locomotor speed.HighlightsZebrafish larvae generate swims of increased speed during optomotor response when D1-like receptors are activated.D1-like receptor activation increases the extent of tail bending during forward swims and turns resulting in increased swim speed.Neuromodulation via D1-like receptors increases motor drive by enhancing excitability of ‘slow’ motor neurons. In addition, D1-like receptor activation recruits quiescent ‘fast’ motor neurons to increase swim speed.This demonstrates neuromodulatory selection of motor neurons belonging to different ‘speed’ modules to alter swimming behavior.Graphical abstract

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