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W O Friesen

Publications and source records attributed to W O Friesen.

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Synchronized oscillatory activity in leech neurons induced by calcium channel blockers.

1. Leech ganglia were superfused with salines in which Ca2+ was replaced with equimolar concentrations of Co2+, Ni2+, or Mn2+. These salines elicited rhythmic membrane potential oscillations with cycle periods ranging from 8 to 25 s in all neurons examined within the ventral nerve cord. 2. Rhythmic activity consisted of a rapid depolarization to a prolonged (3-6 s) plateau level, followed by a rapid repolarization. Each depolarization elicited a burst of action potentials. Peak-to-trough amplitudes of the plateau depolarizations were up to 40 mV in some cells. The plateau depolarizations were separated by slowly depolarizing ramp potentials. 3. Oscillations in all neurons were synchronized (in phase) both within individual ganglia and between ganglia linked by connective nerves. Rhythmic activity in isolated ganglia persisted after the interposed connective nerves were cut. 4. The occurrence of oscillatory activity was strongly correlated with the block of chemical synaptic transmission. 5. Electrotonic interactions persisted during oscillatory activity and may be one mechanism by which oscillations are synchronized. 6. The phase of rhythmic impulse bursts monitored with extracellular electrodes could be reset by electrical stimulation of connective nerves but not by injection of current pulses into individual neurons. Phase reset appeared to occur within one cycle and to a fixed phase point (plateau termination). 7. Oscillatory activity was eliminated by 75-100% reductions of [Na+]o (Na+ replaced with N-methyl-D-glucamine). Smaller reductions of Na+ (by 25-50%) increased the cycle period of oscillations. 8. The Na(+)-K+ pump inhibitors ouabain and strophanthidin disrupted oscillations. Cells were depolarized by approximately 20 mV and fired tonically. After the initial washout of the inhibitors, cells repolarized and became quiescent. After several minutes of continued washing, oscillatory activity resumed. 9. A conceptual model is proposed to explain the mechanisms underlying oscillatory activity induced by Ca2+ channel blockers. According to this model, depolarizing plateaus are generated by a noninactivating Na+ conductance. Na+ influx during the plateau leads to an increase in [Na+]i, which activates an electrogenic Na(+)-K+ pump that contributes to plateau termination. 10. A quantitative computer simulation incorporating six types of currents (capacity, outward rectifying potassium, inward rectifying potassium, sodium, leakage, and an electrogenic sodium pump) demonstrates the plausibility of the conceptual model. 11. These data suggest that a novel Na(+)-based mechanism for membrane potential oscillation is revealed by blockade of Ca2+ channels in leech ganglia.

Animals

Modification of leech behavior patterns by reserpine-induced amine depletion.

A single injection of 100 micrograms reserpine into the crop of the medicinal leech, Hirudo medicinalis, reduced CNS serotonin and dopamine levels to less than 1% of control values within 3 d. High-pressure liquid chromotography- (HPLC) determined CNS serotonin and dopamine levels remained maximally depressed for approximately 1 month following reserpine injection. Subsequently, amine levels recovered slowly, but remained depressed 6 months after reserpine injection. Following reserpine treatment, glyoxylic acid-induced fluorescence or neutral red staining closely mirrored the HPLC-determined time course of amine depletion and recovery. Acute exposure of isolated ganglia to 10 microM reserpine for periods up to 6 hr produced a 20-30% reduction of serotonin and dopamine content. The threshold concentration of reserpine necessary to produce amine depletion was approximately 1 microM. We found that reserpine treatment eliminated biting behavior within 4 d following injection. Biting behavior remained depressed below control levels for approximately 4 months, but returned to control values while CNS serotonin and dopamine levels remained significantly depressed at this time. Unexpectedly, reserpine treatment increased rather than reduced the duration of stimulus-evoked swimming activity. This behavioral change was evident within 3 d and persisted for approximately 3.5 months. To rapidly restore amine levels in reserpine-treated animals, we bathed intact leeches in pond water containing serotonin, dopamine, or octopamine. We found that biting behavior was restored following reserpine treatment by bathing intact leeches in pond water containing serotonin or dopamine, but not octopamine. Also contrary to expectations, the increase in swim duration was not reversed by bath exposure to serotonin, dopamine, octopamine, or histamine. However, all swimming activity in reserpine-treated leeches was eliminated by the amine antagonist cyproheptadine. We propose that the presence of low levels of amines is critical for the expression of both biting and swimming activity in leeches. However, the minimal levels of amines necessary for the expression of these behaviors are lower for swimming than for biting.

Animals

Neuronal generation of the leech swimming movement.

The swimming movement of the leech is produced by an ensemble of bilaterally symmetric, rhythmically active pairs of motor neurons present in each segmental ganglion of the ventral nerve cord. These motor neurons innervate the longitudinal muscles in dorsal or ventral sectors of the segmental body wall. Their duty cycles are phase-locked in a manner such that the dorsal and ventral body wall sectors of any given segment undergo an antiphasic contractile rhythm and that the contractile rhythms of different segments form a rostrocaudal phase progression. This activity rhythm is imposed on the motor neurons by a central swim oscillator, of which four bilaterally symmetric pairs of interneurons present in each segmental ganglion appear to constitute the major component. These interneurons are linked intra- and intersegmentally via inhibitory connections to form a segmentally iterated and inter-segmentally concatenated cyclic neuronal network. The network appears to owe its oscillatory activity pattern to the mechanism of recurrent cyclic inhibition.

Action Potentials

Neural circuits for generating rhythmic movements.

Inasmuch as the identified neural circuits discussed in this review pertain only to the nervous systems of two invertebrate species, one may ask whether or not these findings are generally applicable to central nervous oscillators that generate rhythmic movements in animals of other species and phyla, particularly in the vertebrates. This question is not easy to answer at this time, because detailed cellular network analyses thus far have been possible only in a very few neurophysiologically favorable preparations, such as those presented by the cardiac and stomatogastric ganglia of the lobster and the segmental ganglion of the leech. Nevertheless it is significant that the mechanisms according to which these invertebrate circuits are now thought to generate their oscillations--endogenous rhythmic polarization, reciprocal inhibition, and recurrent cyclic inhibition--were all first proposed to account for generation of rhythmic movements in vertebrate animals (7-9, 51, 71, 79). Moreover, the pattern of motor neuron activity in rhythmic movements of vertebrates is not necessarily more complex than the corresponding pattern in analogous movements of invertebrates. Therefore, the very much greater number of neurons in the central nervous system of vertebrates does not necessarily imply a greater complexity of the central oscillators that generate their rhythmic movements; it may only place greater obstacles in the way of identifying the underlying neuronal circuitry. In any case, it is worthy of note that the current list of fundamentally different and theoretically plausible types of neuronal oscillators is not only quite short but also of long standing. Thus, on these grounds, it seems reasonable to expect that the identified circuits discussed here will prove to be of general applicability to the generation of rhythmic movements in the whole animal kingdom.

Animals

Neuronal control of swimming in the medicinal leech. IV. Identification of a network of oscillatory interneurones.

Four oscillatory interneurones that appear to be the principal components of the central swim oscillator of Hirudo medicinalis have been identified on each side of the segmental ganglia of the ventral nerve cord. During 'swimming' episodes of an isolated nerve cord preparation each interneurone undergoes a polarization rhythm that is phase-locked with the impulse burst rhythm of the motor neurones known to drive the swimming movement. Passage of current into any of the interneurones can shift the phase of the swim rhythm. One of the interneurones projects its axon rearward to posterior ganglia and the other three project their axons frontward to anterior ganglia. The oscillatory interneurones are connected both intra- and interganglionically to form a topologically complex intersegmental network of concatenated ring circuits that possess the feature of recurrent cyclic inhibition. Theoretical analysis and electronic analogue models show that the network is inherently oscillatory and can produce both a cycle period and intra- and intersegmental phase relations of its elements that are appropriate for generating the body wave of the swimming movement.

Animals

Neuronal control of swimming in the medicinal leech. V. Connexions between the oscillatory interneurones and the motor neurones.

A network of intra- and intersegmental synaptic connexions has been identified in the ventral nerve cord of the leech that links the set of oscillatory interneurones of the central swim oscillator to the motor neurones commanding the swimming rhythm. Excitatory connexions lead from oscillatory interneurones to both excitatory and inhibitory motor neurones, whereas inhibitory connexions lead from oscillatory interneurones to only the inhibitory motor neurones. Connexions leading from a motor neurone back to the oscillatory interneurones were found in only one exceptional case, an inhibitory motor neurone previously known to have access to the central swim oscillator. This network of identified connexions can account reasonably well for the mechanism by which the oscillatory interneurones drive their follower motor neurones into the phasic activity pattern characteristic of the swimming movement.

Action Potentials

The analysis of nonlinear synaptic transmission.

In order to characterize synaptic transmission at a unitary facilitating synapse in the lobster cardiac ganglion, a new nonlinear systems analysis technique for discrete-input systems was developed and applied. From the output of the postsynaptic cell in response to randomly occurring presynaptic nerve impulses, a set of kernels, analogous to Wiener kernels, was computed. The kernels up to third order served to characterize, with reasonable accuracy, the input-output properties of the synapse. A mathematical model of the synapse was also tested with a random impulse train and model predictions were compared with experimental synaptic output. Although the model proved to be even more accurate overall than the kernel characterization, there were slight but consistent errors in the model's performance. These were also reflected as differences between model and experimental kernels. It is concluded that a random train analysis provides a comprehensive and objective comparison between model and experiment and automatically provides an arbitrarily accurate characterization of a system's input-output behavior, even in complicated cases where other approaches are impractical.

Animals

An oscillatory neuronal circuit generating a locomotory rhythm.

A quartet of interconnected interneurons whose periodic activity appears to generate the traveling body wave of the swimming leech has been identified on each side of segmental ganglia of the ventral nerve cord of Hirudo medicinalis. Theoretical analysis and electronic analog models of the identified intra- and interganglionic synaptic connections of the segmentally iterated interneurons showed that they form an oscillatory network with cycle period and intra-and intersegmental phase relations appropriate for the swimming movement.

Animals