Modulation of Cellular and Synaptic Variability in the Lamprey Spinal Cord (original) (raw)
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Synaptic Variability Introduces State-Dependent Modulation of Excitatory Spinal Cord Synapses
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 Mg 2+ 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.
Developmental differences in neuromodulation and synaptic properties in the lamprey spinal cord
Neuroscience, 2007
Functional properties in the spinal cord change during development to adapt motor outputs to differing behavioral requirements. Here, we have examined whether there are also developmental differences in spinal cord plasticity by comparing the neuromodulatory effects of substance P in the larval lamprey spinal cord with its previously characterized effects in premigratory adults.
The tachykinin substance P modulates the lamprey locomotor network by increasing the frequency of NMDA-evoked ventral root bursts and by making the burst activity more regular. These effects can last in excess of 24 hr. In this paper, the effects of substance P on the synaptic and cellular properties of motor neurons and identified network interneurons have been examined. Substance P potentiated the amplitude of monosynaptic glutamatergic inputs from excitatory interneurons and reticu-lospinal axons. The amplitude and frequency of miniature EPSPs was increased, suggesting that the synaptic modulation was mediated presynaptically and postsynaptically. The postsynaptic modulation was caused by a specific effect of substance P on the NMDA component of the synaptic input, whereas the presynaptic component was calcium-independent. Substance P did not affect monosynaptic glycin-ergic inputs from lateral interneurons, crossed inhibitory inter-neurons, or ipsilateral segmental interneurons or postsynaptic GABA A or GABA B responses, suggesting that it has little effect on inhibitory synaptic transmission. At the cellular level, substance P increased synaptic inputs, resulting in membrane potential oscillations in motor neurons, crossed caudal interneurons, lateral interneurons, and excita-tory interneurons. The spiking in response to depolarizing current pulses was increased in motor neurons, lateral interneu-rons, and excitatory interneurons, but usually was reduced in crossed inhibitory interneurons. Substance P reduced the calcium-dependent afterhyperpolarization after an action potential in motor neurons and lateral interneurons, but did not affect this conductance in excitatory or crossed inhibitory interneurons. The relevance of these cellular and synaptic changes to the modulation of the locomotor network is discussed.
Synaptically evoked membrane potential oscillations induced by substance P in lamprey motor neurons
Journal of neurophysiology, 2002
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 th...
Variable Properties in a Single Class of Excitatory Spinal Synapse
Although synaptic properties are specific to the type of synapse examined, there is evidence to suggest that properties can vary in individual synaptic populations. Here, a large sample of monosynaptic connections made by excitatory interneurons (EINs) onto motor neurons in the lamprey spinal cord locomotor network has been used to examine the properties of a single class of spinal synapse in detail. The properties and activity-dependent plasticity of EIN-evoked EPSPs varied considerably. This variability occurred at convergent inputs made by several EINs onto single motor neurons. This suggests that it was an intrinsic network property and not simply related to differences between animals or experiments. The activity-dependent plasticity of EIN-evoked EPSPs could be negatively or positively related to the initial EPSP amplitude (P1 and P2 connections, respectively). This reflected the development of facilitation and depression from either small or large initial EPSPs. To identify differences in presynaptic properties that could contribute to the synaptic variability, the quantal amplitude, release probability, number of release sites, and size of the available vesicle pool were examined. This analysis suggested that the variable amplitude and plasticity of EPSPs at P1 and P2 connections reflected an interaction between the release probability and the size of the available transmitter store. There is thus significant functional variability in EIN synaptic properties. Synapses ranged from strong (evoked postsynaptic spikes) to weak (small depressing EPSPs). The selection of interneurons with different synaptic properties could provide an intrinsic mechanism for modifying excitatory network interactions and the locomotor network output.
Paired intracellular recordings have been used to examine the activity-dependent plasticity and neuromodulator-induced metaplasticity of synaptic inputs from identified inhibitory and excitatory interneurons in the lamprey spinal cord. Trains of spikes at 5–20 Hz were used to mimic the frequency of spiking that occurs in network interneurons during NMDA or brainstem-evoked locomotor activity. Inputs from inhibitory and excitatory interneurons exhibited similar activity-dependent changes, with synaptic depression developing during the spike train. The level of depression reached was greater with lower stimulation frequencies. Significant activity-dependent depression of inputs from excitatory interneurons and inhibitory crossed caudal in-terneurons, which are central elements in the patterning of network activity, usually developed between the fifth and tenth spikes in the train. Because these interneurons typically fire bursts of up to five spikes during locomotor activity, this activity-dependent plasticity will presumably not contribute to the patterning of network activity. However, in the presence of the neuromodulators substance P and 5-HT, significant activity-dependent metaplasticity of these inputs developed over the first five spikes in the train. Substance P induced significant activity-dependent depression of inhibitory but potentiation of excitatory interneuron inputs, whereas 5-HT induced significant activity-dependent potentiation of both inhibitory and excita-tory interneuron inputs. Because these metaplastic effects are consistent with the substance P and 5-HT-induced modulation of the network output, activity-dependent metaplasticity could be a potential mechanism underlying the coordination and modulation of rhythmic network activity.
Patch clamp analysis of excitatory synapses in mammalian spinal cord slices
Pflugers Archiv European Journal of Physiology, 1990
Excitatory synaptic transmission to visually identified e-moto neurones was studied in thin slice preparations of the neonatal rat spinal cord. Excitatory postsynaptic currents (EPSCs) elicited by stimulation of intraspinal presynaptic fibres were recorded using the whole-cell patch clamp technique, following blockade of inhibitory transmission by bath application of strychnine and bicuculline. The EPSCs could be separated pharmacologically into N-methyl-D-aspartate-(NMDA) and non-NMDA-receptor-mediated components, where the contribution of the NMDA-mediated component was significant only at holding potentials more positive than -50mV. Graded stimulation of intraspinal fibres showed that the NMDA-and the non-NMDA-mediated EPSCs were evoked by activation of presynaptic fibres with similar sensitivities to the stimulation intensity, suggesting that the same presynaptic fibres released the excitatory amino-acid (EAA) activating the two sub-sets of receptors. Studies of the amplitude fluctuations of EPSCs elicited by stimulation of a presumed single fibre revealed similar proportions of transmission failures and similar distributions of both the NMDA-and the non-NMDA-mediated components. These similarities suggest that the EAA transmitter activating the two sub-types of receptors is released from the same set of synaptic boutons and that the receptors are therefore postsynaptically co-localized. In addition the gamma aminobutyric acidB (GABAB) receptor agonist L-baclofen, which is known to decrease transmitter release, changed the amplitude distributions ofnon-NMDA-and NMDAreceptor-mediated EPSCs into unimodal distributions without affecting the amplitude of the presumed unitary event. The similarity between the transmitter release profiles of the two EAA components further supports the notion of postsynaptic receptor co-localization.