 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
Previous Article | Next Article
The Journal of Neuroscience, March 15, 1999, 19(6):2102-2112
Spontaneous Network Activity Transiently Depresses Synaptic Transmission in the Embryonic Chick Spinal Cord
Brent Fedirchuk1, Peter Wenner2, Patrick J. Whelan2, Stephen Ho3, Joel Tabak2, and Michael J. O'Donovan2 1 Department of Physiology, University of Manitoba, Winnipeg, Manitoba R3E 3J7, Canada, 2 Laboratory of Neural Control, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4455, and 3 Department of Developmental Neurobiology, Research School of Biological Sciences, Australian National University, Canberra 2601, Australia
ABSTRACT
Top
Abstract
Introduction
We examined the effects of spontaneous or evoked episodes of rhythmic activity on synaptic transmission in several spinal pathways of embryonic day 9-12 chick embryos. We compared the amplitude of synaptic potentials evoked by stimulation of the ventrolateral funiculus (VLF), the dorsal or ventral roots, before and after episodes of activity. With the exception of the short-latency responses evoked by dorsal root stimulation, the potentials were briefly potentiated and then reduced for several minutes after an episode of rhythmic activity. Their amplitude progressively recovered in the interval between successive episodes. The lack of post-episode depression in the short-latency component of the dorsal root evoked responses is probably attributable to the absence of firing in cut muscle afferents during an episode of activity.
The post-episode depression of VLF-evoked potentials was mimicked by prolonged stimulation of the VLF, subthreshold for an episode of activity. By contrast, antidromically induced motoneuron firing and the accompanying calcium entry did not depress VLF-evoked potentials recorded from the stimulated ventral root. In addition, post-episode depression of VLF-evoked synaptic currents was observed in voltage-clamped spinal neurons. Collectively, these findings suggest that somatic postsynaptic activity and calcium entry are not required for the depression. We propose instead that the mechanism may involve a form of long-lasting activity-induced synaptic depression, possibly a combination of transmitter depletion and ligand-induced changes in the postsynaptic current accompanying transmitter release. This activity-dependent depression appears to be an important mechanism underlying the occurrence of spontaneous activity in developing spinal networks.
Key words: synaptic depression; spontaneous activity; spinal networks; synaptic currents; chick embryo; rhythmic activity
INTRODUCTION
Spontaneous activity is a characteristic feature of developing synaptic networks and has been detected in many parts of the immature nervous system (Landmesser and O'Donovan, 1984
; Lippe, 1995
Recently, we and others (Streit, 1993
Preliminary reports of this work have been published in abstract form (Fedirchuk and O'Donovan 1996
MATERIALS AND METHODS Experiments were performed on the isolated spinal cord of White Leghorn chicken embryos (embryonic days 9-12). The embryo was removed from the shell, rapidly decapitated, and placed in cooled (10-14°C), oxygenated Tyrode's solution (in mM: 139 NaCl, 12 glucose, 17 NaHCO3, 3 KCl, 1 MgCl2, and 3 CaCl2). The lower thoracic and lumbosacral spinal cord together with attached spinal or peripheral nerves were dissected under a microscope. Using a fine tungsten needle, parts of the VLF were peeled off the spinal cord, rostral to the lumbosacral enlargement (T5-LS1; rVLF) and caudally within the lumbosacral enlargement (LS4-LS6; cVLF). The preparation was then slowly warmed to room temperature (18-24°C) and transferred to a recording chamber where it was secured with insect pins or nylon webbing. The cord was superfused with oxygenated Tyrode's solution and slowly warmed to 27-28°C. Suction electrodes were placed on the dorsal roots (DRs), ventral roots (VRs), rVLF, and cVLF. Neural activity was recorded with high-gain DC amplifiers (3 KHz, Grass P16; World Precision Instruments DAM70, or custom made at National Institutes of Health). Activity was either spontaneous or elicited by electrical stimulation (2-65 µA, 50-500 µsec) of the cord. Neural recordings were digitized (Neuro-corder DR-886, Neuro Data Instruments) and recorded on videotape for later analysis using custom computer software. In some experiments, the evoked potentials were filtered at 0.01-500 Hz and digitized (1 kHz) using a analog-to-digital board (General Instruments). Data are presented as means ± SEM.
Whole-cell recordings. Recordings were made from single motoneurons and presumptive interneurons using the blind patch technique (Blanton et al., 1989
. The patch solution contained (in mM): 130 KMeSO3, 10 NaCl, 1.1 EGTA, 10 HEPES, 1 Na2ATP, 1 MgCl2, and 1 CaCl2. Recordings were obtained by slowly advancing the electrode through the ventral surface of the lumbosacral cord. Slight positive pressure was applied to the electrode during its advance. When the electrode was in the gray matter and a slight resistance change was observed, the positive pressure was removed, and light suction was applied. If a stable gigaohm seal was formed, a pulse of suction was used to rupture the membrane. Intracellular recordings were made using an Axoclamp 2A amplifier (series resistance uncompensated) in current- or voltage-clamp mode.
Neurons were distinguishable from glia by their ability to produce action potentials in response to intracellular current injection. Neurons (n = 29) were included in the study if their resting membrane potential was more negative than
40 mV. Four of these cells were identified as motoneurons by antidromic stimulation from the sartorius muscle nerve (n = 3) or the ventral root (n = 1), and two were identified as VLF interneurons by antidromic stimulation of the VLF. The reminder (n = 23) were not antidromically activated from either source.
Imaging. Ventral roots were loaded with a 25-50% solution of calcium green dextran in 0.2% Triton X-100 (O'Donovan et al., 1993
RESULTS Our strategy was to investigate the effects of spontaneous activity on several distinct pathways we knew to be active during an episode. The first was the pathway from the VLF onto both motoneurons and interneurons. This was selected because previous work had shown that some of the interneurons projecting into the VLF were active during spontaneous episodes (O'Donovan et al., 1994
We were also interested in comparing the effects of spontaneous activity on synaptic transmission in a pathway that was not active during spontaneous episodes. For this reason we examined the projection from the cut dorsal roots onto motoneurons (Lee et al., 1988
Modulation of VLF-evoked potentials by spontaneous episodes of activity
Electrical stimulation of either the rostral or the caudal VLF evoked synaptic potentials in the ventral roots and in the unstimulated part of the VLF (Fig. 1). These potentials were prolonged and sometimes had distinct short- and long-latency components (Fig. 1B, b). Previous work has shown that the early component of the VLF-evoked response (Fig. 1B, b, arrow) is probably generated by monosynaptic and disynaptic projections, whereas the long-latency responses reflect recruitment within a recurrently connected population of interneurons (Ritter, Wenner, Ho, Whelan, and O'Donovan, unpublished data; also see Is postsynaptic activity required for the depression? and Discussion).
View larger version (26K):[in this window]
[in a new window]
Figure 1. VLF-evoked potentials recorded in both the ventral roots and VLF are initially potentiated (asterisks) and then reduced after a spontaneous episode of rhythmic activity. A, VR and VLF recordings on a slow time scale. The rostral VLF was stimulated repetitively at 0.1 Hz. Examples of the evoked potentials produced in the VR and VLF are shown on a faster time scale in B. The short-latency component of the VLF-evoked responses is indicated by the arrows in B. Traces b
After either a spontaneous or an evoked episode, the VLF-evoked potentials were initially potentiated and then depressed (Fig. 1B). Potentiation was observed throughout the episode and as the episode depolarization was decaying (Fig. 1A, asterisk). This potentiation presumably occurred because transmission through polysynaptic pathways was facilitated while the neurons were depolarized (because the intercalated interneurons would be close to, or suprathreshold for, action potentials). Consistent with this interpretation, we found that the potentiation was particularly marked for the long-latency, polysynaptic components of the evoked response (Fig. 1B, b and b
We quantified the time course of the depression by stimulating the VLF once every 10 sec in the interval between episodes and measuring the amplitude of the potentials evoked in the ventral roots and the VLF. Figure 2 illustrates the time course of recovery for an individual experiment and pooled data from several experiments. The individual (Fig. 2A) and pooled (Fig. 2B) ventral root data are shown on a non-normalized time scale to illustrate the time course of the recovery. The evoked potentials decayed from their initial potentiation and reached a minimum amplitude ~1-2 min after the end of the episode. At this time the potentials evoked in the ventral roots had declined to 39 ± 3% of their control value just before the episode (n = 3 experiments; Fig. 2B). VLF-evoked potentials recorded from the VLF behaved similarly and exhibited their maximal depression (52 ± 4% of control) 1-2 min after the end of the episode (n = 5 experiments; Fig. 2C). After this minimum, the amplitude of the potentials recovered progressively until the next episode. We found considerable interexperiment variability in the extent of the depression. For example for the five experiments used to construct the graph of Figure 2C (VLF
VLF), the maximal depression ranged from 40-82% of the pre-episode control amplitude. We have not investigated the source of this variability. Among the factors that could be involved are the number and type of axons recruited by the test stimulus and the duration and intensity of network activation during episodes. Although the depression was quantitatively variable from embryo to embryo it was, nevertheless, a robust phenomenon and was observed in every preparation.
View larger version (22K):[in this window]
[in a new window]
Figure 2. Time course of the depression and recovery of VLF-evoked potentials recorded from the ventral roots and from the VLF after an episode of spontaneous activity. A, The time course of the changes in the normalized peak amplitude of the VLF-evoked potentials recorded from a ventral root is plotted for a single experiment. Sample potentials are shown above the graph at the times indicated. The vertical bars indicate the time of spontaneous episodes. B, Average of three experiments to show the time course of the depression and recovery of VLF-evoked potentials recorded from the VRs. C, Average of five experiments showing the time course of the depression and its recovery for VLF-evoked potentials recorded from the VLF. Notice in C the time base has been normalized for comparison with subsequent figures. In B and C data are plotted as the mean ± SEM. The pooled data were measured from a single interepisode interval in each experiment.
Modulation of recurrent, motoneuronal responses by spontaneous episodes of activity
In the next set of experiments, we sought to establish whether the post-episode depression was expressed in another pathway we knew was active during spontaneous episodes. For this reason, we chose the pathway mediating recurrent connections between motoneurons (Whelan and O'Donovan, 1997
-
Hz).
View larger version (18K):[in this window]
[in a new window]
Figure 3. Ventral root evoked ventral root potentials are transiently depressed after an episode. A, Potentials recorded from the LS4 ventral root in response to stimulation of the LS3 ventral root at various times after a spontaneous episode. B, Time course of the changes in the normalized peak amplitude of the recurrent ventral root potentials for the experiment illustrated in A. The timing of the evoked responses shown in A is illustrated by the lowercase letters on the graph. C, Average of four experiments to show the time course of the changes in the recurrent ventral root potentials. The interepisode intervals have been normalized in B and C, and the occurrence of spontaneous episodes is indicated by the vertical bars. Data are plotted as mean ± SEM. Stimulus parameters: 150-300 µsec; 5-35 µA; stimulus rate,
Modulation of dorsal root afferent pathways by spontaneous episodes of activity
Dorsal root evoked potentials were initially potentiated (Fig. 4A, asterisk) and then depressed by a spontaneous episode. However, only the late component of the dorsal root-evoked responses was affected. The short-latency response recorded from the ventral roots or the VLF was largely unchanged after the episode (Fig. 4B,C, arrows). After an episode the short-latency component of the dorsal root evoked response was 111 ± 17% of the pre-episode control amplitude in the ventral roots (n = 4 experiments) and 93 ± 10% of the pre-episode control amplitude in the VLF (n = 3 experiments). By contrast, the long-latency component was reduced to 12 ± 6% of the control amplitude in the ventral roots (n = 4 experiments) and to 12 ± 7% of the control amplitude in the VLF (n = 3 experiments). These results are consistent with the idea that the inactive dorsal root projections onto motoneurons or interneurons, which are responsible for the short-latency responses, are not subject to post-episode depression. Although the dorsal roots are subject to primary afferent depolarization (PAD) during an episode (Ho and O'Donovan, 1993
View larger version (17K):[in this window]
[in a new window]
Figure 4. A, Ventral root potentials evoked by DR stimulation are transiently potentiated (asterisk) and then depressed after an episode of rhythmic activity. B, Dorsal root evoked responses recorded in the ventral root (DR
Is postsynaptic activity required for the depression?
The first point we wanted to establish was whether the occurrence of an episode was required for the depression or whether prolonged activity alone would be sufficient. For this reason we stimulated the VLF with a train (4-10 Hz for 30 sec), subthreshold for an episode, and determined the effect on the VLF-evoked responses recorded from the ventral roots (Fig. 5A,B). This type of VLF stimulation caused a long-lasting depression, similar to that after an episode, in the amplitude of the evoked synaptic potentials. For example, in the experiment illustrated in Figure 5A the amplitude of the VLF-evoked potential recorded from the ventral roots declined to 48% of its prestimulus control level after the stimulus train applied to the VLF. In the same experiment, a spontaneous episode depressed the VLF-evoked potential to 28% of the control value. In three experiments the VLF train depressed the VLF-evoked responses to 56 ± 7% of the control value, whereas spontaneous activity depressed the VLF-evoked potentials to 39 ± 7% of the control amplitude. These findings are consistent with the idea that neural activity is responsible for the depression, but we cannot exclude the possibility that other processes, occurring during the episode, could also contribute.
View larger version (12K):[in this window]
[in a new window]
Figure 5. Comparison between the effects of prolonged stimulation of the VLF and spontaneous activity on the depression of VLF-evoked responses recorded from the ventral roots. A, Curves comparing the normalized amplitude of VLF-evoked potentials recorded in the ventral roots before and after a spontaneous episode (spont, filled circles) or a train of stimuli applied to the VLF (4 Hz for 30 sec; stim, filled squares). The vertical bar indicates the occurrence of an episode or the stimulus train. The VLF was stimulated once every 10 sec, and three successive responses were averaged to obtain each data point. Above the graph are sample records of the VLF-evoked responses before (a) and after (b, c) the VLF train obtained at the times indicated by the lowercase letters on the graph. B, Plots comparing the normalized amplitude of VLF-evoked potentials recorded in the ventral roots before and after a spontaneous episode or a stimulus train applied to the VLF pooled from three experiments. The stimulus train was 30 sec long and varied from 4 to 10 Hz. The vertical bar indicates the time of the episode or the stimulus train. Data are shown as mean ± SEM. The data for the spontaneous episodes are the same as those plotted the first part of the graph (up to 3 min) of Figure 2B.
In the next set of experiments, we sought to establish whether the post-episode depression depended on the state of the cells in which the potentials were evoked. We knew that changes in input resistance could not account for the depression, because the input resistance of spinal neurons increases 1-2 min after an episode and then progressively falls until the next episode (Chub and O'Donovan, 1995
View larger version (29K):[in this window]
[in a new window]
Figure 6. The post-episode depression of VLF-evoked synaptic currents occurs in voltage-clamped spinal neurons. A, Example of a VLF-evoked synaptic current recorded in an unidentified lumbosacral neuron before and 2 min after an episode of activity. The traces are averaged from 10 successive stimuli given at Hz. B, Normalized synaptic currents evoked by VLF stimulation in a ventrally located spinal neuron. The VLF was stimulated once every 5 sec. The bottom panel shows three evoked currents obtained at the times indicated by the letters over the traces. Arrows in the inset indicate the stimulus artifact. C, Post-episode depression and recovery of voltage-clamped synaptic currents averaged from three sartorius motoneurons, including one that was not modulated (mean ± SEM). D, Post-episode depression and recovery of voltage-clamped synaptic currents averaged from nine unidentified, ventrally located neurons (mean ± SEM). Vertical bars indicate the occurrence of evoked episodes.
The post-episode recovery of the voltage-clamped synaptic currents is illustrated in Figure 6B. In this experiment, the stimulus intensity applied to the VLF was low, resulting in considerable fluctuations in the amplitude of the evoked, probably monosynaptic, synaptic current. Nevertheless, there was a clear depression in the currents after the episode, reaching a minimum 1-2 min after the episode. Similar findings were made in 10 of 14 other cells, including 2 sartorius motoneurons and 8 unidentified spinal neurons (Fig. 6C,D). In four cells (one sartorius motoneuron and three unidentified cells) no modulation of the synaptic current was seen. The absence of modulation in these cells may have been the result of cellular damage. None of the four cells exhibited the potentiation that occurs during the episode, which is consistently recorded from the ventral roots, the muscle nerves, and the majority (11 of 12) of neurons displaying post-episode depression of the evoked currents. This potentiation is believed to occur because polysynaptic pathways are facilitated when neurons are depolarized during the episode. It should, therefore, be detected in a healthy cell.
These experiments demonstrated that the post-episode depression occurred in spinal neurons in which firing, membrane potential changes, and calcium entry at the soma were prevented by voltage clamp. In the next set of experiments, we extended these observations by investigating whether the post-episode depression occurred in motoneurons induced to fire antidromically rather than synaptically. For this purpose, we antidromically stimulated motoneurons through their axons in a ventral root and monitored the effects on the VLF-evoked potentials recorded from the same ventral root. Antidromic stimulation activates motoneurons directly and also "Renshaw-like" interneurons to which the motoneuron collaterals connect. These interneurons project back to motoneurons and also connect with other spinal interneurons (Wenner et al., 1998
The ventral roots were stimulated at 5-10 Hz to deliver 200-500 pulses. VLF stimuli were delivered at
Hz before and after the antidromic train, and the evoked responses were monitored from the ventral root that was stimulated antidromically. In the experiment shown in Figure 7, motoneurons in LS1 were loaded with calcium green dextran, and the fluorescence changes were monitored during stimulation of the LS1 ventral root (Fig. 7, Antidromic) and also during the occurrence of a spontaneous episode (Fig. 7, Spontaneous). The VLF-evoked potentials recorded from LS1 (or other roots) were not depressed after the antidromic train and continued their upward trajectory as they recovered from the previous spontaneous episode. By contrast, a spontaneous episode depressed the evoked potentials (Fig. 7). Although not illustrated, the potentials fully recovered after the episode, and the preparation continued to generate robust activity.
View larger version (11K):[in this window]
[in a new window]
Figure 7. Antidromic activation of motoneurons does not depress VLF-evoked potentials recorded from the stimulated ventral root. The graph plots the normalized amplitude of the VLF-evoked potentials recorded from the LS1 ventral root before and after antidromic stimulation of the LS1 ventral root (Antidromic) and before and after the occurrence of a spontaneous episode (Spontaneous). Also shown on the same time scale are the fluorescence changes recorded simultaneously from LS1 motoneurons back-filled with calcium green dextran.
Similar findings were made in another experiment in which the motoneurons were labeled with calcium green dextran and in three other experiments in which calcium imaging was not used. Thirty to 60 sec after the end of the antidromic train, the amplitude of the evoked potentials was 103 ± 3% of the control (range, 93-112%; n = 5 experiments). In the same experiments VLF-evoked potentials were reduced to 76 ± 4% of the control amplitude after a spontaneous episode (range, 69-86%, n = 4 experiments). Although the post-episode depression recorded in these experiments was less marked than in some of the other experiments, presumably because of interexperiment variation (see Modulation of VLF-evoked potentials by spontaneous episodes of activity), this is unlikely to explain the absence of depression after the antidromic train. Not only was the depression consistently observed after each episode, it was never seen after the antidromic train. More compellingly, however, the antidromic train failed to interrupt the recovery from depression caused by a previous episode (Fig. 7). Collectively, therefore, these experiments indicate that the firing and calcium entry accompanying antidromic stimulation are insufficient to depress the synaptic potentials evoked in motoneurons.
Finally, we wanted to ensure that the VLF-evoked synaptic potentials did not exhibit an unusual voltage dependence that might explain their depression after an episode. This was important because spinal neurons are hyperpolarized by as much as 10 mV after an episode. This hyperpolarization recovers as a depolarizing ramp in the interval between episodes (Chub and O'Donovan, 1995
DISCUSSION We have described a long-lasting depression of synaptic transmission in several pathways of the embryonic spinal cord after spontaneous episodes of rhythmic activity. The depression recovers with a time course similar to the interval between spontaneously occurring episodes. This prolonged synaptic depression represents a new form of activity-dependent plasticity that may underlie the expression of periodic activity by developing spinal networks.
Where is the site of the post-episode depression of synaptic potentials?
Depression of short-latency responses
The shortest latency VLF-evoked synaptic potentials are probably mediated through monosynaptic and disynaptic connections. The shortest latency responses recorded intracellularly had a latency of <10 msec (see Fig. 6), which means they are almost certainly mediated monosynaptically. In addition, our previous work has shown that the average latency of VLF-evoked potentials recorded in spinal interneurons was 9 msec (Ritter, Wenner, Ho, Whelan, and O'Donovan, unpublished data). By comparison, monosynaptic muscle afferent EPSPs evoked in motoneurons (over a similar conduction distance) have an average latency of 10 msec, whereas polysynaptic EPSPs have a minimum latency of 16 msec (Lee and O'Donovan, 1991Depression of long-latency responses
The amplitude of long-latency polysynaptic responses will depend on the efficacy of synaptic transmission at individual synapses and, second, the extent and time course of interneuronal recruitment triggered by the test stimulus. Our previous work has shown that ventral spinal neurons are subject to a slow depolarization in the interval between episodes (Chub and O'Donovan, 1995
View larger version (31K):[in this window]
[in a new window]
Figure 8. A, Schematic to illustrate the hypothesized circuitry underlying afferent and VLF-evoked responses in motoneurons and their changes after an episode of rhythmic activity. The state of the network before (Pre-episode) and after (Post-episode) an episode is shown in A. In each case the diagram illustrates the neurons activated by a single stimulus applied to the VLF (Stim. VLF). Neurons in red are activated directly by the VLF stimulus and contribute to the short-latency (<50 msec) responses evoked in the ventral root. Neurons in blue are activated polysynaptically by the VLF stimulus and contribute to the long-latency ventral root potentials. B, VLF-evoked ventral root potentials, with the short-latency component in red and the long-latency component in blue, corresponding to the pre- and post-episode network configurations shown in A. C, DR-evoked ventral root potentials, with the short-latency component in black (unmodulated) and the long-latency component in blue. Before an episode we hypothesize that VLF stimulation activates both direct (red) and indirect, polysynaptic (blue) pathways to motoneurons. The polysynaptic pathways are proposed to constitute a network of recurrently connected interneurons that can also be activated by the dorsal roots (dorsal root activation patterns of the network are not illustrated but would be similar to the VLF activation patterns). Before the episode, a suitable stimulus intensity applied to the VLF can activate a significant polysynaptic component. However, after the episode synaptic transmission is depressed at active synapses (asterisks). As a consequence, the short-latency direct responses are depressed, and the number of polysynaptic neurons recruited by the stimulus is reduced, resulting in a decrease in the long-latency component of the response. Notice that the primary afferent dorsal root synapses (arrows) are not depressed after an episode, because they are not firing during the episode. As a result, the short-latency dorsal root evoked responses in the ventral root are not depressed (black component of responses shown in C). However, the afferent axons also project to the recurrently connected population of interneurons, which are active during the episode. Therefore, the long-latency component of the dorsal root responses (blue) is depressed after the episode.
Is postsynaptic activity required for the expression of the depression?
In several parts of the nervous system, depolarization, firing, or calcium entry can alter the conductance of ligand-gated receptors on the cell membrane and even influence presynaptic transmitter release by a retrograde mechanism (Pitler and Alger, 1992
Collectively, these results suggest that somatic activity is not responsible for the depression. Therefore, we can exclude mechanisms for the regulation of synaptic transmission that depend on postsynaptic somatic depolarization (Pitler and Alger, 1992
It remains possible that dendritic calcium entry and depolarization could mediate the depression we have observed. Such dendritic effects would probably not be influenced by the voltage clamp used in our experiments or by antidromic invasion of motoneurons, unless the spikes invaded the dendrites. Resolving this issue will require the technically difficult task of recording from the dendrites of embryonic spinal neurons.
Role of synaptic depression in the expression of spontaneous episodic activity
Activity-dependent synaptic depression has been proposed as an important mechanism in the expression of spontaneous activity by recurrently connected, excitatory networks (Streit, 1993
At present, it is not known whether activity-dependent synaptic depression is present in other developing networks that express spontaneous, episodic activity. Some form of refractoriness has been postulated to be involved in wave dynamics in the developing retina, but its mechanism is unknown (Feller et al., 1997
FOOTNOTES Received Aug. 26, 1998; revised Dec. 28, 1998; accepted Jan. 5, 1999.
B.F. was the recipient of a Medical Research Council of Canada fellowship. P.J.W. was a recipient of a Natural Sciences and Engineering Research Council of Canada fellowship and an Alberta Heritage Foundation for Medical Research Fellowship.
Correspondence should be addressed to M. J. O'Donovan, Laboratory of Neural Control, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Building 49, Room 3A50, 49 Convent Drive, Bethesda, MD 20892-4455.
REFERENCES
- Alger BE, Pitler TA (1995) Retrograde signaling at GABAA-receptor synapses in the mammalian CNS. Trends Neurosci 18:333-340[Web of Science][Medline].
- Blanton MG, Le Turco JJ, Kriegstein AR (1989) Whole cell recording from neurons in slices of reptilian and mammalian cerebral cortex. J Neurosci Methods 30:203-210[Web of Science][Medline].
- Chub N, O'Donovan MJ (1995) Multi-functional actions of GABA in the regulation of spontaneous activity in the isolated spinal cord of the chick embryo. Soc Neurosci Abstr 21:688.
- Chub N, O'Donovan MJ (1998a) Blockade and recovery of spontaneous rhythmic activity following application of neurotransmitter antagonists to spinal networks of the chick embryo. J Neurosci 18:294-306
[Abstract/Free Full Text] .- Chub N, O'Donovan MJ (1998b) Miniature postsynaptic currents and their modulation by spontaneous activity in the E11-E12 chick embryo spinal cord. Soc Neurosci Abstr 24:1315.
- Davis GW, DiAntonio A, Petersen SA, Goodman CS (1998) Postsynaptic PKA controls quantal size and reveals a retrograde signal that regulates presynaptic transmitter release in Drosophila. Neuron 20:305-315[Web of Science][Medline].
- Fedirchuk B, O'Donovan MJ (1996) Evoked potentials are transiently depressed following rhythmic activity in the embryonic chick spinal cord. Soc Neurosci Abstr 22:1377.
- Feller MB, Butts DA, Aaron HL, Rokhsar DS, Shatz CJ (1997) Dynamic processes shape spatiotemporal properties of retinal waves. Neuron 19:293-306[Web of Science][Medline].
- Garaschuk O, Hanse E, Konnerth A (1998) Developmental profile and synaptic origin of early network oscillations in the CA1 region of rat neonatal hippocampus. J Physiol (Lond) 507:219-236
[Abstract/Free Full Text] .- Ho S, O'Donovan MJ (1993) Regionalization and inter-segmental coordination of rhythm generating networks in the spinal cord of the chick embryo. J Neurosci 13:1345-1371.
- Itaya SK, Fortin S, Molotchnikoff S (1995) Evolution of spontaneous activity in the rat developing superior colliculus. Can J Pharmacol 73:1372-1377.
- Katz LC, Shatz CJ (1996) Synaptic activity and the construction of cortical circuits. Science 274:1133-1138
[Abstract/Free Full Text] .- Kirkwood A, Lee HK, Bear MF (1995) Co-regulation of long-term potentiation and experience-dependent synaptic plasticity in visual cortex by age and experience. Nature 375:328-331[Medline].
- Landmesser LT, O'Donovan MJ (1984) Activation patterns of embryonic chick hindlimb muscles recorded in-ovo and in an isolated spinal cord preparation. J Physiol (Lond) 347:189-204
[Abstract/Free Full Text] .- Lee MT, O'Donovan MJ (1991) Organization of hindlimb muscle afferent projections to lumbosacral motoneurons in the chick embryo. J Neurosci 11:2564-2573[Abstract].
- Lee MT, Koebbe MJ, O'Donovan MJ (1988) The development of sensorimotor synaptic connections in the lumbosacral spinal cord of the chick embryo. J Neurosci 8:2530-2543[Abstract].
- Lev-Tov A, Pinco M (1992) In vitro studies of prolonged synaptic depression in the neonatal rat spinal cord. J Physiol (Lond) 447:149-169
[Abstract/Free Full Text] .- Lippe WR (1995) Relationship between frequency of spontaneous bursting and tonotopic position in the developing avian auditory system. Brain Res 703:205-213[Web of Science][Medline].
- Maeda E, Robinson HP, Kawana A (1995) The mechanisms of generation and propagation of synchronized bursting in developing networks of cortical neurons. J Neurosci 15:6834-6845
[Abstract/Free Full Text] .- McLean HA, Caillard O, Ben-Ari Y, Gaiarsa JL (1996) Bidirectional plasticity expressed by GABAergic synapses in the neonatal rat hippocampus. J Physiol (Lond) 496:471-477
[Abstract/Free Full Text] .- Mendelson B, Frank E (1991) Specific monosynaptic sensory-motor connections form in the absence of patterned neural activity and motoneuronal cell death. J Neurosci 11:1390-1403[Abstract].
- Mozrzymas JW, Cherubini E (1998) Changes in intracellular calcium concentration affect desensitization of GABAA receptors in acutely dissociated P2-P6 rat hippocampal neurons. J Neurophysiol 79:1321-1328
[Abstract/Free Full Text] .- Nishimaru H, Iizuka M, Ozaki S, Kudo N (1996) Spontaneous motoneuronal activity mediated by glycine and GABA in the spinal cord of rat fetuses in vitro. J Physiol (Lond) 497:131-143
[Abstract/Free Full Text] .- O'Donovan MJ (1989) Motor activity in the isolated spinal cord of the chick embryo: synaptic drive and firing pattern of single motoneurons. J Neurosci 9:943-958[Abstract].
- O'Donovan MJ, Chub N (1997) Population behavior and self-organization in the genesis of spontaneous rhythmic activity by developing spinal networks. Semin Cell Dev Biol 8:21-28[Web of Science][Medline].
- O'Donovan MJ, Ritter A (1995) Rhythmic activity patterns of motoneurons and interneurons in the embryonic chick spinal cord. In: Neural control of movement (Ferrell WR, Proske U, eds), pp 195-201. New York: Plenum.
- O'Donovan MJ, Ho S, Sholomenko G, Yee W (1993) Real-time imaging of neurons retrogradely and anterogradely labeled with calcium sensitive dyes. J Neurosci Methods 46:91-106[Web of Science][Medline].
- O'Donovan MJ, Ho S, Yee W (1994) Calcium imaging of rhythmic network activity in the developing spinal cord of the chick embryo. J Neurosci 14:6354-6369[Abstract].
- O'Donovan MJ, Chub N, Wenner P (1998a) Mechanisms of spontaneous activity in developing spinal networks. J Neurobiol 37:131-145[Web of Science][Medline].
- O'Donovan MJ, Wenner P, Chub N, Tabak J, Rinzel J (1998b) Mechanisms of spontaneous activity in the developing spinal cord and their relevance to locomotion. In: Neuronal mechanisms for generating locomotor activity (Kiehn O, Harris-Warrick RM, Jordan LM, Hultborn H, Kudo N, eds), pp 130-141. New York: New York Academy of Sciences.
- Pitler TA, Alger BE (1992) Postsynaptic spike firing reduces synaptic GABAA responses in hippocampal pyramidal cells. J Neurosci 12:4122-4132[Abstract].
- Roche KW, Tingley WG, Huganir RL (1994) Glutamate receptor phosphorylation and synaptic plasticity. Curr Opin Neurobiol 4:383-388[Medline].
- Senn W, Wyler K, Streit J, Larkum M, Luscher H-R, Mey H, Muller L, Stainhauser D, Vogt K, Wannier Th (1996) Dynamics of a random neural network with synaptic depression. Neural Networks 9:575-588.[Web of Science]
- Sernagor E, O'Donovan MJ (1991) Whole-cell patch clamp recordings from rhythmically active motoneurons in the isolated spinal cord of the chick embryo. Neurosci Lett 128:211-216[Web of Science][Medline].
- Sernagor E, Chub N, Ritter A, O'Donovan MJ (1995) Pharmacological characterization of the rhythmic synaptic drive onto lumbosacral motoneurons in the chick embryo spinal cord. J Neurosci 15:7452-7464[Abstract].
- Soltesz I, Mody I (1995) Ca(2+)-dependent plasticity of miniature inhibitory postsynaptic currents after amputation of dendrites in central neurons. J Neurophysiol 73:1763-1773
[Abstract/Free Full Text] .- Staley KJ, Longacher M, Bains JS, Yee A (1998) Presynaptic modulation of CA3 network activity. Nat Neurosci 1:201-209.[Web of Science][Medline]
- Streit J (1993) Regular oscillations of synaptic activity in spinal networks in vitro. J Neurophysiol 70:871-878
[Abstract/Free Full Text] .- Tabak J, O'Donovan MJ (1998) Statistical analysis and intersegmental delays reveal possible roles of network depression in the generation of spontaneous activity in the chick embryo spinal cord. In: Neuronal mechanisms for generating locomotor activity (Kiehn O, Harris-Warrick RM, Jordan LM, Hultborn H, Kudo N, eds), pp 428-431. New York: New York Academy of Sciences.
- Tabak J, Senn W, O'Donovan MJ, Rinzel J (1999) Comparison of two models for pattern generation based on synaptic depression. Neurocomputing, in press.
- Wenner P, Matise M, Joyner A, O'Donovan MJ (1998) Physiological and molecular characterization of interneurons in the developing spinal cord. In: Neuronal mechanisms for generating locomotor activity (Kiehn O, Harris-Warrick RM, Jordan LM, Hultborn H, Kudo N, eds), pp 425-427. New York: New York Academy of Sciences.
- Whelan PJ, O'Donovan MJ (1997) The development of recurrent connections in the embryonic chick. Soc Neurosci Abstr 23:770.2.
- Wong RO, Chernjavsky A, Smith SJ, Shatz CJ (1995) Early functional neural networks in the developing retina. Nature 374:716-718[Medline].
Copyright © 1999 Society for Neuroscience 0270-6474/99/1962102-11$05.00/0
This article has been cited by other articles:
S. Wang, L. Polo-Parada, and L. T. Landmesser
Characterization of Rhythmic Ca2+ Transients in Early Embryonic Chick Motoneurons: Ca2+ Sources and Effects of Altered Activation of Transmitter Receptors
J. Neurosci., December 2, 2009; 29(48): 15232 - 15244.
[Abstract] [Full Text] [PDF]
C. Gonzalez-Islas, N. Chub, and P. Wenner
NKCC1 and AE3 Appear to Accumulate Chloride in Embryonic Motoneurons
J Neurophysiol, February 1, 2009; 101(2): 507 - 518.
[Abstract] [Full Text] [PDF]
S. Crisp, J. F. Evers, A. Fiala, and M. Bate
The development of motor coordination in Drosophila embryos
Development, November 15, 2008; 135(22): 3707 - 3717.
[Abstract] [Full Text] [PDF]
P. Han, S. T. Nakanishi, M. A. Tran, and P. J. Whelan
Dopaminergic Modulation of Spinal Neuronal Excitability
J. Neurosci., November 28, 2007; 27(48): 13192 - 13204.
[Abstract] [Full Text] [PDF]
J. Jones, E. A. Stubblefield, T. A. Benke, and K. J. Staley
Desynchronization of Glutamate Release Prolongs Synchronous CA3 Network Activity
J Neurophysiol, May 1, 2007; 97(5): 3812 - 3818.
[Abstract] [Full Text] [PDF]
H. Xu, P. J. Whelan, and P. Wenner
Development of an Inhibitory Interneuronal Circuit in the Embryonic Spinal Cord
J Neurophysiol, May 1, 2005; 93(5): 2922 - 2933.
[Abstract] [Full Text] [PDF]
C. Marchetti, J. Tabak, N. Chub, M. J. O'Donovan, and J. Rinzel
Modeling Spontaneous Activity in the Developing Spinal Cord Using Activity-Dependent Variations of Intracellular Chloride
J. Neurosci., April 6, 2005; 25(14): 3601 - 3612.
[Abstract] [Full Text] [PDF]
U. A. Wiedemann and A. Luthi
Timing of Network Synchronization By Refractory Mechanisms
J Neurophysiol, December 1, 2003; 90(6): 3902 - 3911.
[Abstract] [Full Text] [PDF]
M. G. Hanson and L. T. Landmesser
Characterization of the Circuits That Generate Spontaneous Episodes of Activity in the Early Embryonic Mouse Spinal Cord
J. Neurosci., January 15, 2003; 23(2): 587 - 600.
[Abstract] [Full Text] [PDF]
A. Rozzo, L. Ballerini, G. Abbate, and A. Nistri
Experimental and Modeling Studies of Novel Bursts Induced by Blocking Na+ Pump and Synaptic Inhibition in the Rat Spinal Cord
J Neurophysiol, August 1, 2002; 88(2): 676 - 691.
[Abstract] [Full Text] [PDF]
A. R Houweling, M. Bazhenov, I. Timofeev, F. Grenier, M. Steriade, and T. J Sejnowski
Frequency-selective augmenting responses by short-term synaptic depression in cat neocortex
J. Physiol., July 15, 2002; 542(2): 599 - 617.
[Abstract] [Full Text] [PDF]
R. E. Harris, M. G. Coulombe, and M. B. Feller
Dissociated Retinal Neurons Form Periodically Active Synaptic Circuits
J Neurophysiol, July 1, 2002; 88(1): 188 - 195.
[Abstract] [Full Text] [PDF]
H.-H. Chen, J. W. Yip, A. F. R. Stewart, and E. Frank
Differential expression of a transcription regulatory factor, the LIM domain only 4 protein Lmo4, in muscle sensory neurons
Development, January 11, 2002; 129(21): 4879 - 4889.
[Abstract] [Full Text] [PDF]
K. J. Staley, J. S. Bains, A. Yee, J. Hellier, and J. M. Longacher
Statistical Model Relating CA3 Burst Probability to Recovery From Burst-Induced Depression at Recurrent Collateral Synapses
J Neurophysiol, December 1, 2001; 86(6): 2736 - 2747.
[Abstract] [Full Text] [PDF]
J. Tabak, J. Rinzel, and M. J. O'Donovan
The Role of Activity-Dependent Network Depression in the Expression and Self-Regulation of Spontaneous Activity in the Developing Spinal Cord
J. Neurosci., November 15, 2001; 21(22): 8966 - 8978.
[Abstract] [Full Text] [PDF]
N. S. Bradley
Age-Related Changes and Condition-Dependent Modifications in Distribution of Limb Movements During Embryonic Motility
J Neurophysiol, October 1, 2001; 86(4): 1511 - 1522.
[Abstract] [Full Text] [PDF]
P. Wenner and M. J. O'Donovan
Mechanisms That Initiate Spontaneous Network Activity in the Developing Chick Spinal Cord
J Neurophysiol, September 1, 2001; 86(3): 1481 - 1498.
[Abstract] [Full Text] [PDF]
N. Chub and M. J. O'Donovan
Post-Episode Depression of GABAergic Transmission in Spinal Neurons of the Chick Embryo
J Neurophysiol, May 1, 2001; 85(5): 2166 - 2176.
[Abstract] [Full Text] [PDF]
P. Wenner, M. J. O'Donovan, and M. P. Matise
Topographical and Physiological Characterization of Interneurons That Express Engrailed-1 in the Embryonic Chick Spinal Cord
J Neurophysiol, November 1, 2000; 84(5): 2651 - 2657.
[Abstract] [Full Text] [PDF]
S. M. Johnson and G. S. Mitchell
Activity-Dependent Plasticity of Descending Synaptic Inputs to Spinal Motoneurons in an In Vitro Turtle Brainstem-Spinal Cord Preparation
J. Neurosci., May 1, 2000; 20(9): 3487 - 3495.
[Abstract] [Full Text] [PDF]
J. Tabak, W. Senn, M. J. O'Donovan, and J. Rinzel
Modeling of Spontaneous Activity in Developing Spinal Cord Using Activity-Dependent Depression in an Excitatory Network
J. Neurosci., April 15, 2000; 20(8): 3041 - 3056.
[Abstract] [Full Text] [PDF]
D. Parker
Activity and Calcium-Dependent Mechanisms Maintain Reliable Interneuron Synaptic Transmission in a Rhythmic Neural Network
J. Neurosci., March 1, 2000; 20(5): 1754 - 1766.
[Abstract] [Full Text] [PDF]
N. S. Bradley and C. Sebelski
Ankle Restraint Modifies Motility at E12 in Chick Embryos
J Neurophysiol, January 1, 2000; 83(1): 431 - 440.
[Abstract] [Full Text] [PDF]
P. Wenner and M. J. O'Donovan
Identification of an Interneuronal Population that Mediates Recurrent Inhibition of Motoneurons in the Developing Chick Spinal Cord
J. Neurosci., September 1, 1999; 19(17): 7557 - 7567.
[Abstract] [Full Text] [PDF]
This Article Abstract 
Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager 
Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (39) Citing Articles via Google Scholar Google Scholar Articles by Fedirchuk, B. Articles by O'Donovan, M. J. Search for Related Content PubMed PubMed Citation Articles by Fedirchuk, B. Articles by O'Donovan, M. J.
|
|
|
|
 |
|