Modulation of Cellular and Synaptic Variability in the Lamprey Spinal Cord

2007 ◽  
Vol 97 (1) ◽  
pp. 44-56 ◽  
Author(s):  
David Parker ◽  
Sarah Bevan

Variability is increasingly recognized as a characteristic feature of cellular, synaptic, and network properties. While studies have traditionally focused on mean values, significant effects can result from changes in variance. This study has examined cellular and synaptic variability in the lamprey spinal cord and its modulation by the neuropeptide substance P. Cellular and synaptic variability differed in different types of cell and synapse. Substance P reduced the variability of subthreshold locomotor-related depolarizations and spiking in motor neurons during network activity. These effects were associated with a reduction in the variability of spiking in glutamatergic excitatory network interneurons and with a reduction in the variance of excitatory interneuron-evoked excitatory postsynaptic potentials (EPSPs). Substance P also reduced the variance of postsynpatic potentials (PSPs) from crossing inhibitory and excitatory interneurons, but it increased the variance of inhibitory postsynpatic potentials (IPSPs) from ipsilateral inhibitory interneurons. The effects on the variance of different PSPs could occur with or without changes in the PSP amplitude. The reduction in the variance of excitatory interneuron-evoked EPSPs was protein kinase A, calcium, and N-methyl-d-aspartate (NMDA) dependent. The NMDA dependence suggested that substance P was acting postsynaptically. This was supported by the reduced variability of postsynaptic responses to glutamate by substance P. However, ultrastructural analyses suggested that there may also be a presynaptic component to the modulation, because substance P reduced the variability of synaptic vesicle diameters in putative glutamatergic terminals. These results suggest that cellular and synaptic variability can be targeted for modulation, making it an additional source of spinal cord plasticity.

2002 ◽  
Vol 87 (1) ◽  
pp. 113-121 ◽  
Author(s):  
Erik Svensson ◽  
Sten Grillner ◽  
David Parker

Short-lasting application (10 min) of tachykinin neuropeptides evokes long-lasting (>24 h) modulation of N-methyl-d-aspartate (NMDA)-evoked locomotor network activity in the lamprey spinal cord. In this study, the net effects of the tachykinin substance P on the isolated spinal cord have been examined by recording from motor neurons in the absence of NMDA and ongoing network activity. Brief bath application of substance P (30 s to 2 min) induced irregular membrane potential oscillations in motor neurons. These oscillations consisted of depolarizing and hyperpolarizing phases and were associated with phasic ventral-root activity. The oscillations were blocked by the tachykinin antagonist spantide II. They were also blocked by tetrodotoxin (TTX), suggesting that they were not dependent on intrinsic membrane properties of the motor neurons but were synaptically mediated. Substance P could also have a direct effect, however, because a membrane potential depolarization persisted in the presence of TTX. Protein kinase agonists and antagonists were used to investigate the intracellular pathways through which substance P acted. The oscillations were blocked by the selective protein kinase C (PKC) antagonist chelerythrine. However, the TTX-resistant membrane potential depolarization was not significantly affected by blocking PKC. The protein kinase A and G antagonist H8 did not affect either the oscillations or the direct TTX-resistant membrane potential depolarization. The glutamate receptor antagonist kynurenic acid abolished the substance-P-evoked oscillations, suggesting that they were dependent on glutamate release. The oscillations were abolished or reduced by the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxalene-2,3-dione but were only reduced by the NMDA receptor antagonist d-AP5. The oscillations were thus mediated by glutamatergic inputs with a greater dependence on non-NMDA receptors. Blocking glycinergic inputs with strychnine resulted in large depolarizing plateaus and bursts of spikes. The glutamatergic and glycinergic inputs underlying the oscillations are apparently evoked through direct and indirect excitatory effects on inhibitory and excitatory premotor interneurons. Substance P thus has a distributed excitatory effect in the spinal cord. While it can activate premotor networks, this activation alone is not able to evoke a coordinated behaviorally relevant motor output.


Science ◽  
2020 ◽  
Vol 370 (6515) ◽  
pp. 431-436
Author(s):  
Sandeep Kishore ◽  
Eli B. Cadoff ◽  
Moneeza A. Agha ◽  
David L. McLean

In vertebrates, faster movements involve the orderly recruitment of different types of spinal motor neurons. However, it is not known how premotor inhibitory circuits are organized to ensure alternating motor output at different movement speeds. We found that different types of commissural inhibitory interneurons in zebrafish form compartmental microcircuits during development that align inhibitory strength and recruitment order. Axonal microcircuits develop first and provide the most potent premotor inhibition during the fastest movements, followed by perisomatic microcircuits, and then dendritic microcircuits that provide the weakest inhibition during the slowest movements. The conversion of a temporal sequence of neuronal development into a spatial pattern of inhibitory connections provides an “ontogenotopic” solution to the problem of shaping spinal motor output at different speeds of movement.


1999 ◽  
Vol 81 (4) ◽  
pp. 1730-1740 ◽  
Author(s):  
Maria Ullström ◽  
David Parker ◽  
Erik Svensson ◽  
Sten Grillner

Neuropeptide-mediated facilitation and inhibition of sensory inputs and spinal cord reflexes in the lamprey. The effects of neuromodulators present in the dorsal horn [tachykinins, neuropeptide Y (NPY), bombesin, and GABAB agonists] were studied on reflex responses evoked by cutaneous stimulation in the lamprey. Reflex responses were elicited in an isolated spinal cord preparation by electrical stimulation of the attached tail fin. To be able to separate modulator-induced effects at the sensory level from that at the motor or premotor level, the spinal cord was separated into three pools with Vaseline barriers. The caudal pool contained the tail fin. Neuromodulators were added to this pool to modulate sensory inputs evoked by tail fin stimulation. The middle pool contained high divalent cation or low calcium Ringer to block polysynaptic transmission and thus limit the input to the rostral pool to that from ascending axons that project through the middle pool. Ascending inputs and reflex responses were monitored by making intracellular recordings from motor neurons and extracellular recordings from ventral roots in the rostral pool. The tachykinin neuropeptide substance P, which has previously been shown to potentiate sensory input at the cellular and synaptic levels, facilitated tail fin-evoked synaptic inputs to neurons in the rostral pool and concentration dependently facilitated rostral ventral root activity. Substance P also facilitated the modulatory effects of tail fin stimulation on ongoing locomotor activity in the rostral pool. In contrast, NPY and the GABAB receptor agonist baclofen, both of which have presynaptic inhibitory effects on sensory afferents, reduced the strength of ascending inputs and rostral ventral root responses. We also examined the effects of the neuropeptide bombesin, which is present in sensory axons, at the cellular, synaptic, and reflex levels. As with substance P, bombesin increased tail fin stimulation-evoked inputs and ventral root responses in the rostral pool. These effects were associated with the increased excitability of slowly adapting mechanosensory neurons and the potentiation of glutamatergic synaptic inputs to spinobulbar neurons. These results show the possible behavioral relevance of neuropeptide-mediated modulation of sensory inputs at the cellular and synaptic levels. Given that the types and locations of neuropeptides in the dorsal spinal cord of the lamprey show strong homologies to that of higher vertebrates, these results are presumably relevant to other vertebrate systems.


2007 ◽  
Vol 97 (4) ◽  
pp. 2769-2779 ◽  
Author(s):  
Huaying Xu ◽  
Arthur Clement ◽  
Terrence Michael Wright ◽  
Peter Wenner

Locally projecting inhibitory interneurons play a crucial role in the patterning and timing of network activity. However, because of their relative inaccessibility, little is known about their development or incorporation into circuits. In this report we demonstrate that the GABAergic R-interneuron circuit undergoes a reorganization in the chick embryo spinal cord between embryonic days 8 and 15 (E8 and E15). R-interneurons receive synaptic input from and project back to motoneurons. By stimulating motoneurons projecting in one ventral root and recording the disynaptic response from motoneurons in adjacent segments, we show that the output of the R-interneuron circuit is reorganized during development. After stimulation of the LS2 ventral root, disynaptic responses observed in whole cell recordings became more common and stronger for LS3 motoneurons and less common for the more distant LS4 motoneurons from E8 to E10. Optical studies demonstrated that R-interneurons activated by LS2 stimulation were restricted to the LS2 segment and had a small glutamatergic component at both E8 and E10, but that more R-interneurons were activated within the segment by E10. The recruitment of more LS2 R-interneurons at E10 is likely to contribute to stronger projections to LS3 motoneurons, but the fact that fewer LS4 motoneurons receive this input is more consistent with a functional refinement of the more distant projection of the GABAergic R-interneuron. Interestingly, this pattern of reorganization was not observed throughout the rostrocaudal extent of the cord, introducing the possibility that refinement could serve to remove connections between functionally unrelated interneurons and motoneurons.


Life ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 100
Author(s):  
Alexandra Proshchina ◽  
Victoria Gulimova ◽  
Anastasia Kharlamova ◽  
Yuliya Krivova ◽  
Valeriy Barabanov ◽  
...  

Spaceflight may cause hypogravitational motor syndrome (HMS). However, the role of the nervous system in the formation of HMS remains poorly understood. The aim of this study was to estimate the effects of space flights on the cytoskeleton of the neuronal and glial cells in the spinal cord and mechanoreceptors in the toes of thick-toed geckos (Chondrodactylus turneri GRAY, 1864). Thick-toed geckos are able to maintain attachment and natural locomotion in weightlessness. Different types of mechanoreceptors have been described in the toes of geckos. After flight, neurofilament 200 immunoreactivity in mechanoreceptors was lower than in control. In some motor neurons of flight geckos, nonspecific pathomorphological changes were observed, but they were also detected in the control. No signs of gliosis were detected after spaceflight. Cytoskeleton markers adequately reflect changes in the cells of the nervous system. We suggest that geckos’ adhesion is controlled by the nervous system. Our study revealed no significant disturbances in the morphology of the spinal cord after the prolonged space flight, supporting the hypothesis that geckos compensate the alterations, characteristic for other mammals in weightlessness, by tactile stimulation.


Author(s):  
Bernard Kripkee ◽  
Robert C. Froemke

Plasticity of inhibitory synapses keeps inhibition in balance and in register with excitation when changes occur in excitatory synapses. Inhibition has many functions to perform, and there are many kinds of inhibitory neurons to perform various computations and regulate network activity. Different forms of long-term changes in inhibitory synapses have been demonstrated that depend on neural activity. Inhibitory plasticity appears to be partly responsible for the specificity of the inhibitory connections needed to carry out some inhibitory functions. The evolving story of cortical inhibitory plasticity shows that different types of inhibitory interneurons play different roles in a variety of inhibitory functions, that several types of inhibitory plasticity have been attested, and that different forms of plasticity can be expected to have different effects on the organization and specificity of inhibitory connections.


2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
David Parker

The relevance of neuronal and synaptic variability remains unclear. Cellular and synaptic plasticity and neuromodulation are also variable. This could reflect state-dependent effects caused by the variable initial cellular or synaptic properties or direct variability in plasticity-inducing mechanisms. This study has examined state-dependent influences on synaptic plasticity at connections between excitatory interneurons (EIN) and motor neurons in the lamprey spinal cord. State-dependent effects were examined by correlating initial synaptic properties with the substance P-mediated plasticity of low frequency-evoked EPSPs and the reduction of the EPSP depression over spike trains (metaplasticity). The low frequency EPSP potentiation reflected an interaction between the potentiation of NMDA responses and the release probability. The release probability introduced a variable state-dependent subtractive influence on the postsynaptic NMDA-dependent potentiation. The metaplasticity was also state-dependent: it was greater at connections with smaller available vesicle pools and high initial release probabilities. This was supported by the significant reduction in the number of connections showing metaplasticity when the release probability was reduced by high Mg2+Ringer. Initial synaptic properties thus introduce state-dependent influences that affect the potential for plasticity. Understanding these conditions will be as important as understanding the subsequent changes.


2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S452-S452
Author(s):  
Noritaka Murakami ◽  
Masahiro Sakurai ◽  
Takashi Horinouchi ◽  
Jun Ito ◽  
Shin Kurosawa ◽  
...  

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