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M Raastad

Publications and source records attributed to M Raastad.

12 recordsLinked to original sources
PubMed2004

Activity-dependent excitability changes in hippocampal CA3 cell Schaffer axons.

The membrane potential changes following action potentials in thin unmyelinated cortical axons with en passant boutons may be important for synaptic release and conduction abilities of such axons. In the lack of intra-axonal recording techniques we have used extracellular excitability testing as an indirect measure of the after-potentials. We recorded from individual CA3 soma in hippocampal slices and activated the axon with a range of stimulus intensities. When conditioning and test stimuli were given to the same site the excitability changes were partly masked by local effects of the stimulating electrode at intervals < 5 ms. Therefore, we elicited the conditioning action potential from one axonal branch and tested the excitability of another branch. We found that a single action potential reduced the axonal excitability for 15 ms followed by an increased excitability for approximately 200 ms at 24 degrees C. Using field recordings of axonal action potentials we show that raising the temperature to 34 degrees C reduced the magnitude and duration of the initial depression. However, the duration of the increased excitability was very similar (time constant 135 +/- 20 ms) at 24 and 34 degrees C, and with 2.0 and 0.5 mM Ca2+ in the bath. At stimulus rates > 1 Hz, a condition that activates a hyperpolarization-activated current (Ih) in these axons, the decay was faster than at lower stimulation rates. This effect was reduced by the Ih blocker ZD7288. These data suggest that the decay time course of the action potential-induced hyperexcitability is determined by the membrane time constant.

Action Potentials↗
PubMed2003

Unmyelinated axons in the rat hippocampus hyperpolarize and activate an H current when spike frequency exceeds 1 Hz.

The mammalian cortex is densely populated by extensively branching, thin, unmyelinated axons that form en passant synapses. Some thin axons in the peripheral nervous system hyperpolarize if action potential frequency exceeds 1-5 Hz. To test the hypothesis that cortical axons also show activity-induced hyperpolarization, we recorded extracellularly from individual CA3 pyramidal neurons while activating their axon with trains consisting of 30 electrical stimuli. Synaptic excitation was blocked by kynurenic acid. We observed a positive correlation between stimulation strength and the number of consecutive axonal stimuli that resulted in soma spikes, suggesting that the threshold increased as a function of the number of spikes. During trains without response failures there was always a cumulative increase in the soma response latency. Intermittent failures, however, decreased the latency of the subsequent response. At frequencies of > 1 Hz, the threshold and latency increases were enhanced by blocking the hyperpolarization-activated H current (Ih)by applying the specific Ih blocker ZD7288 (25 microM) or 2 mM Cs+. Under these conditions, response failures occurred after 15-25 stimuli, independent of the stimulation strength. Adding GABA receptor blockers (saclofen and bicuculline) and a blocker of metabotropic glutamate receptors did not change the activity-induced latency increase in recordings of the compound action potential. We interpret these results as an activity-induced hyperpolarization that is partly counteracted by Ih. Such a hyperpolarization may influence transmitter release and the conduction reliability of these axons.

Action Potentials↗
PubMed2000

The hippocampal lamella hypothesis revisited.

We have re-examined the hippocampal lamellar organization of the CA3-to-CA1 connection. Based on a new technique with electrophysiological quantification of Schaffer collateral density, and a review of recent literature, we conclude that the lamellar organization remains a useful concept for understanding hippocampal connectivity. Using a sheet-like hippocampal preparation, containing the whole CA1 region, we mapped the distribution of Schaffer collaterals by two procedures. First, we recorded the amplitude of the Schaffer compound action potential in various parts of CA1 after stimulation of a point in CA3. Second, we charted the CA1 positions from which we could antidromically excite individual CA3 neurones. Although the Schaffer collaterals radiated from their CA3 cells of origin within a wide, fan-shaped area, covering a large part of the septo-temporal extent of CA1, the amplitude of the compound action potential was largest in a slightly oblique, transverse band across the CA1 towards the subicular region.

Action Potentials↗
PubMed2000

Spike coding during locomotor network activity in ventrally located neurons in the isolated spinal cord from neonatal rat.

To characterize spike coding in spinal neurons during rhythmic locomotor activity, we recorded from individual cells in the lumbar spinal cord of neonatal rats by using the on-cell patch-clamp technique. Locomotor activity was induced by N-methyl-D aspartate (NMDA) and 5-hydroxytryptamine (5-HT) and monitored by ventral root recording. We made an estimator based on the assumption that the number of spikes arriving during two halves of the locomotor cycle could be a code used by the neuronal network to distinguish between the halves. This estimator, termed the spike contrast, was calculated as the difference between the number of spikes in the most and least active half of an average cycle. The root activity defined the individual cycles and the positions of the spikes were calculated relative to these cycles. By comparing the average spike contrast to the spike contrast in noncyclic, randomized spike trains we found that approximately one half the cells (19 of 42) contained a significant spike contrast, averaging 1.25 +/- 0.23 (SE) spikes/cycle. The distribution of spike contrasts in the total population of cells was exponential, showing that weak modulation was more typical than strong modulation. To investigate if this low spike contrast was misleading because a higher spike contrast averaged out by occurring at different positions in the individual cycles we compared the spike contrast obtained from the average cycle to its maximal value in the individual cycles. The value was larger (3.13 +/- 0.25 spikes) than the spike contrast in the average cycle but not larger than the spike contrast in the individual cycles of a random, noncyclic spike trains (3.21 +/- 0.21 spikes). This result suggested that the important distinction between cyclic and noncyclic cells was only the repeated cycle position of the spike contrast and not its magnitude. Low spike frequencies (5.2 +/- 0.82 spikes/cycle, that were on average 3.5 s long) and a minimal spike interval of 100-200 ms limited the spike contrast. The standard deviation (SD) of the spike contrast in the individual neurons was similar to the average spike contrasts and was probably stochastic because the SDs of the simulated, noncyclic spike trains were also similar. In conclusion we find a highly distributed and variable locomotor related cyclic signal that is represented in the individual neurons by very few spikes and that becomes significant only because the spike contrast is repeated at a preferred phase of the locomotor cycle.

Action Potentials↗
PubMed1998

Synaptic signaling in an active central network only moderately changes passive membrane properties.

The membrane resistance of mammalian central neurons may be dramatically reduced by synaptic events during network activity, thereby changing their integration properties. We have used the isolated neonatal rat spinal cord to provide measurements of the effect of synaptic signaling on passive membrane properties during network activity. Synaptic signaling could take place during fictive locomotor activity with only modest (on average 35%) reduction of the input resistance (Rin) and of the cell's charging time constant (tauin). Individual synaptic signals, however, often introduced a peak conductance that was greater than the input conductance (Gin = 1/Rin) without synaptic activity. The combination of moderate average synaptic conductance and large conductance of individual synaptic signals suggests that individual presynaptic neurons have large but short-lasting influence on the integration properties of postsynaptic neurons.

Algorithms↗
PubMed1997

Analysis of EPSCs and IPSCs carrying rhythmic, locomotor-related information in the isolated spinal cord of the neonatal rat.

To understand better the synaptic language used by neurons in active networks, we have analyzed postsynaptic currents (PSCs) received by interneurons in the isolated spinal cord from neonatal rats during 5-hydroxytryptamine- and N-methyl--aspartate-induced fictive locomotion. Using a computer algorithm, we identified PSCs in rhythmically active interneurons in laminae VII and X. To test whether the PSCs actually participated in the transmission of the cyclic, locomotor-related signal, we constructed an analytic current trace based on only the identified events. Each identified PSC was fitted by a mathematical function, and the shape of this function was added to a baseline with time delays given by the time positions of the identified PSCs. By averaging the resulting analytic current trace over several cycles, we showed that the identified PSCs built a cyclic signal locked to the rhythmic activity recorded from the ventral roots. Furthermore, subtraction of the analytic from the original current trace reduced the amplitude of the cyclic signal received by these cells. Thus the identified PSCs contributed to the cyclic information, allowing us to analyze how they built the compound cyclic signal. Most often there was an inverse relationship between the contribution from excitatory and inhibitory PSCs during the cyclic modulation, indicating that there was a reciprocal regulation of the presynaptic inhibitory and excitatory cells. Comparing the most inhibitory and most excitatory halves of the locomotor related cycle, there was a considerably larger modulation of the frequency of PSCs than of their amplitude. The small and sometimes insignificant modulation of PSC amplitude suggests that facilitation and depression had little importance for the information transfer. The modest amplitude modification also suggests that the large range of available PSC amplitudes seen in these neurons was not used very efficiently to code the cyclic information.

Animals↗
PubMed1996

Plateau properties in mammalian spinal interneurons during transmitter-induced locomotor activity.

We examined the organization of spinal networks controlling locomotion in the isolated spinal cord of the neonatal rat, and in this study we provide the first demonstration of plateau and bursting mechanisms in mammalian interneurons that show locomotor-related activity. Using tight-seal whole-cell recordings, we characterized the activity of interneurons from spinal regions previously suggested to be involved in locomotor rhythm generation. Most (63%) interneurons showed rhythmic, oscillating membrane potentials in phase with rhythmic ventral root activity induced by the glutamate receptor agonist, N-methyl-D-aspartate and 5-hydroxytryptamine or activation of muscarinic acetylcholine receptors. We focused our attention on these cells because they appeared most likely to be participating in locomotor networks. The rhythmic oscillations of most of these interneurons (88%) appeared to be driven mainly by excitatory and inhibitory synaptic inputs. A smaller number of interneurons, however, also displayed intrinsic plateau properties or bursting capabilities which amplified their response to excitatory input, and which were correlated with the presence of negative slope regions in the steady-state I-V curve, and with the ability to burst in the absence of synaptic drive. Although the bursting properties of these neurons may contribute to the generation of the locomotor rhythm, as suggested previously in studies of lower vertebrates, we suggest that a prime role of intrinsic plateau properties in mammalian locomotor networks is to facilitate or shape and time the propagation of information in the network.

Action Potentials↗
PubMed1996

The number of postsynaptic currents necessary to produce locomotor-related cyclic information in neurons in the neonatal rat spinal cord.

To understand better how synaptic signaling contributes to network activity, we analyzed the potential contribution of putative unitary postsynaptic currents (PSCs) to locomotor-related information received by spinal interneurons in neonatal rats. The average cyclic modulation of the whole-cell current in 13 neurons was quantified as the difference between the current integral (charge) during the first and second halves of the cyclic locomotor network output. Between 7.6 and 303 average unitary PSCs per second were needed to produce the cyclic modulation. This number is so low that very few (1-5) of the synapses contributing to the cyclic information need to be active simultaneously. This suggests that individual presynaptic cells in a central locomotor network can have a powerful influence on other neurons.

Action Potentials↗
PubMed1996

Diversity of postsynaptic amplitude and failure probability of unitary excitatory synapses between CA3 and CA1 cells in the rat hippocampus.

Different CA3 cells may have dissimilar effects on a CA1 pyramidal cell. In order to test this idea, we studied the amplitude distribution of excitatory postsynaptic currents (EPSCs) in response to weak electrical stimulation of presynaptic axons in the rat hippocampal slice. We accepted the response populations as representative for the effect of, in most cases, a single axon when the EPSCs appeared at a certain threshold stimulation strength, with the subsequent lack of increase in amplitude with further stimulation increase. By comparing the EPSC amplitude distributions obtained from different synaptic inputs to the same CA1 cell, we found differences in the failure probability and the EPSC amplitude, each of which contributed to differences in the mean response amplitude. We conclude that not only the number but also the specific subset of active CA3 cells is important for the synaptically driven discharge of a given CA1 cell.

Animals↗
PubMed1995

Extracellular activation of unitary excitatory synapses between hippocampal CA3 and CA1 pyramidal cells.

The possibility of regular activation of unitary excitatory synapses on hippocampal CA1 cells by electrical stimulation of Schaffer collaterals was explored in the rat. The amplitude of the excitatory postsynaptic currents (EPSCs) and failures in response to a range of stimulation intensities around the threshold for the smallest detectable EPSC were analysed. After an abrupt appearance of EPSCs in response to increasing stimulation strength, both EPSC amplitude and failure rate could reach a plateau where increasing stimulation intensity did not cause additional responses. This was interpreted as a regular activation of mainly a single axon. Statistical methods showed, however, that only 12 out of approximately 50 experiments using threshold stimulation were without significant contamination from additional fibres. In this subset of experiments, upper limits for contamination from other fibres were estimated by using bootstrapping methods. More than 90% of the responses were probably due to faithful activation of a single axon, assuming that the density of axons connecting to one target cells is relatively homogeneous. This result makes the described method suitable for examining some aspects of the transmission between individual hippocampal cells.

Animals↗
PubMed1994

Specificity of protein kinase inhibitor peptides and induction of long-term potentiation.

Previous studies have used synthetic peptide analogs, corresponding to sequences within the pseudosubstrate domain of protein kinase C (PKC) or the autoregulatory domain of Ca2+/calmodulin-dependent protein kinase II (CaMKII), in attempts to define the contribution of each of these protein kinases to induction of long-term potentiation (LTP). However, the specificity of these inhibitor peptides is not absolute. Using intracellular delivery to rat CA1 hippocampal neurons, we have determined the relative potency of two protein kinase inhibitor peptides, PKC-(19-36) and [Ala286]CaMKII-(281-302), as inhibitors of the induction of LTP. Both peptides blocked the induction of LTP; however, PKC-(19-36) was 30-fold more potent than [Ala286]CaMKII-(281-302). The relative specificity of PKC-(19-36), [Ala286]CaMKII-(281-302), and several other CaMKII peptide analogs for protein kinase inhibition in vitro was also determined. A comparison of the potencies of PKC-(19-36) and [Ala286]CaMKII-(281-302) in the physiological assay with their Ki values for protein kinase inhibition in vitro indicates that the blockade of induction of LTP observed for each peptide is attributable to inhibition of PKC.

Amino Acid Sequence↗