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M R Park

Publications and source records attributed to M R Park.

33 records · Page 2Linked to original sources
PubMed1993

Early assessment of neurologic deficits in the fluid percussion model of brain injury.

This study was designed to quantify the early neurologic effects of brain injury elicited by fluid percussion to the dura of cats. Propofol was used for surgical anesthesia because recovery in normal animals from an intravenous infusion was found to be nearly complete within 2 h of cessation and absolutely complete by 4 h. In addition, a cat coma scale (CCS) was developed that reflects normal (CCS, 14) to moribund (CCS, 3) behavior. The CCS values at 6 h were compared with the force of injury expressed in atmospheres (atm), maximum blood pressure change, and gross neuropathology to ascertain which parameter might best account for the behavior observed after brain injury. The results showed that decreasing neurologic scores correlated well with increasing atmospheres of injury (Pearson's r 0.71, p < 0.001) but not with the rise in systolic blood pressure caused by the trauma (n = 29). Coma scores did correlate with the cross sectional area of ponto-mesencephalic lesions (Pearson's r = 0.51, p < 0.01) and proved to be significantly different in animals grouped according to lesion size of less or more than 3 mm in length (t test, p < 0.01). Thus the CCS and the pharmacologic properties of propofol permit an early analysis of the neurologic status in the feline fluid percussion model of brain injury. These procedures could facilitate the evaluation of early biochemical changes that affect behavior and of therapies designed to ameliorate the deleterious effects of head injury.

Anesthesia↗
PubMed1989

Capacitance compensation and bridge balance adjustment in intracellular recording from dendritic neurons.

Under most experimental conditions in intracellular recording, the proper adjustment of the amplifier is essential for the interpretation of the signals recorded from neurons. It is considered possible to accurately align the capacitance compensation and bridge balance adjustments of the amplifier simultaneously with the recording of membrane potential of an impaled cell if a number of conditions are met. In the strictest sense, these conditions are met only if: (1) the neuron is isopotential and if its electrical behavior can be adequately described using a single exponential decay constant, and if (2) that decay time constant is much longer than that of the microelectrode. These conditions cannot usually be satisfied. Because intracellular adjustment of capacitance compensation and bridge balance is necessary in many circumstances, it is desirable, to know whether any of the methods for performing these adjustments are accurate when used under less strict constraints, and to assess the nature and degree of the error that can be expected when the constraints are ignored. The results of computer simulations of a simple intracellular recording amplifier, microelectrode and a dendritic neuron model consisting of an isopotential cell and terminated finite equivalent cylinder representation of the dendrites are presented here. These studies show that the introduction of fast components of the response to intracellular current transients by the redistribution of applied charge in dendrite neurons may sometimes make it impossible to correctly apply the conventional methods of capacitance compensation and bridge balance. If the high-frequency response of the intracellular recording amplifier has sufficient fidelity, however, these adjustments can be made to a sufficient degree of accuracy using the response to sine wave calibration signals of varying frequency.

Computer Simulation↗
PubMed1989

Constant current source for iontophoresis.

A simple, battery-powered current source is described that is suitable for the iontophoresis of axonal tracing substances, such as Phaseolus vulgaris leucoagglutinin. Unlike the previous designs that form the basis of most commonly used iontophoretic devices, this circuit does not use operational amplifiers to provide controlled current. Instead, a pair of bipolar transistors that can be selected to provide a compliance of many hundreds of volts form the regulating circuitry.

Amplifiers, Electronic↗
PubMed1988

Interactions between the lateral hypothalamus and the periaqueductal gray.

Anatomical and physiological experiments were conducted to characterize the interactions between the lateral hypothalamus (LH) and the periaqueductal gray (PAG) and to determine the role of neurotensin in their interaction. Anatomical studies using injection of Phaseolus vulgaris leucoagglutinin into the LH showed an extensive projection to the ventromedial and the ventrolateral PAG and a less dense projection to the medial and dorsal parts of this region. Physiological experiments were performed on both deeply and lightly anesthetized animals. Electrical stimulation of the LH caused excitation of PAG cells with an onset latency of approximately 14 msec. There was a strong correlation between the response of PAG cells to electrical stimulation and injection of glutamic acid into the LH. Electrical or chemical stimulation of the LH produced an increase in tail flick latency in the lightly anesthetized animals that outlasted the stimulation period. There was a strong correlation between the response of PAG cells to electrical and chemical stimulation of the LH and their response to pressure-injected neurotensin. It is concluded that an excitatory projection from the LH to PAG exists which may involve neurotensin. This pathway may be involved in the analgesia produced by LH stimulation.

Animals↗
PubMed1987

Intracellular horseradish peroxidase labeling of rapidly firing dorsal raphe projection neurons.

The class of rapidly firing neurons in the dorsal raphe of the rat was examined using extracellular recording and intracellular injection of horseradish peroxidase. Rapidly firing neurons (termed F-cells in this report) continue to fire at high spontaneous rates during intracellular recording. This and their brief (ca. 1 ms) and symmetrical action potentials distinguish them from the slowly firing, presumably serotonergic neurons in dorsal raphe. Intracellular labeling with horseradish peroxidase reveals that F-cells have small (10-15 microns) spherical, multipolar or piriform somata. Somatic spines are sparse or entirely absent. The general form of the dendritic tree is radiant and poorly branching. However, the dendrites of F-cells take two forms, with both forms being present on the same neuron so that besides having a complement of poorly branching dendrites, each F-cell has at least one dendrite with a slightly tufted branching pattern: a short primary dendrite gives rise to 3 or 4 secondary branches. The axons of F-cells project from the nucleus. They align themselves along the trajectories of known dorsal raphe efferent pathways, coursing laterally and ventrorostrally beyond the bounds of the nucleus. Morphometric measurements of retrogradely labeled dorsal raphe projection neurons provide additional evidence that small projection neurons exist.

Action Potentials↗
PubMed1987

Monosynaptic inhibitory postsynaptic potentials from lateral habenula recorded in dorsal raphe neurons.

The inhibitory response evoked in presumably serotonergic dorsal raphe neurons by stimulation of the lateral habenular nucleus was examined in the rat using intracellular recording techniques. Electrical stimulation of the lateral habenula produces a long-lasting hyperpolarization in dorsal raphe neurons having the slow spontaneous firing pattern (0.5-1.5 spikes/sec) and broad action potential (greater than 1 msec) indicative of serotonergic neurons. The hyperpolarizing response is reversed by hyperpolarizing current injection or by increasing intracellular Cl-concentration and is thus an inhibitory postsynaptic potential (IPSP) due to conductance increase to Cl-. The mean latency of the IPSP is 7.0 msec, which implies a mean conduction velocity for habenulo-raphe axons of 1.2 m/sec. The latency of the response could be demonstrated to be unaffected by changes in stimulus strength, indicating that the IPSP is monosynaptic, which is in agreement with recent anatomical data. Intracellular horseradish peroxidase labeling of responding neurons shows them to have a morphology typical of serotonergic dorsal raphe neurons.

Animals↗
PubMed1986

The morphology and divergent axonal organization of midbrain raphe projection neurons in the rat.

The morphology of dorsal raphe neurons was examined using intracellular injections of horseradish peroxidase (HRP) and the Golgi technique. Light microscopic examination of HRP-labeled projection neurons revealed a neuron type with radiating, poorly branched and sparsely spined dendrites and terminal dendritic thickets. The stem axon of these neurons left the nucleus ventrally but gave off a beaded collateral while still within the parent cell's dendritic domain. Somatodendritic morphology from Golgi-Kopsch stained material coincided with intracellular HRP findings and the dorsal raphe may consist of varieties of one basic morphological type of neuron. Intracellular recordings made during the HRP injection experiments confirmed that stimulation of the ventral medial tegmentum elicited an antidromic action potential and an inhibitory postsynaptic potential in dorsal raphe projection neurons. The order of axonal projections arising from the midbrain raphe nuclei was examined using a double retrograde axonal tracing technique. After paired HRP and [3H] wheat germ agglutinin injections within certain projection targets of the dorsal and median raphe neurons (caudate-putamen, amygdala, hippocampus, substantia nigra and locus coeruleus), each target structure was found to have its own unique representation within a topographically distinct portion of one or more of the raphe subgroups. Neurons projecting to the caudate-putamen and substantia nigra occupied rather rostral portions. Neurons projecting to the hippocampus and locus coeruleus resided more caudally. Neurons projecting to the amygdala were situated intermediately. Overall, rostrocaudal topography in the intranuclear distributions of raphe projection neurons resulted in the formation of complex overlap zones where collateralized neurons always resided.

Action Potentials↗
PubMed1983

An intracellular HRP study of the rat globus pallidus. II. Fine structural characteristics and synaptic connections of medially located large GP neurons.

In order to classify the presynaptic elements contacting the principle class of globus pallidus neurons, electron microscopic examination of serial sections made from a medially located large globus pallidus neuron, labeled with intracellular horseradish peroxidase, was undertaken. In addition, the use of labeled and light microscopically reconstructed material allowed us to quantitatively determine the distribution of each bouton type along the soma and dendrites. Six types of presynaptic terminals contacting the labeled cell have been recognized. Type 1 endings, the most numerous (84%), make symmetrical contacts on all portions of the cell, except spines, contain large pleomorphic, and a few large dense-core vesicles. Type 2 endings are filled with small spherical-to-ellipsoidal synaptic vesicles. They make asymmetrical contacts only with higher-order dendrites and account for 12% of synaptic contacts onto the labeled neuron. Type 3 endings are large, contain sparsely distributed large pleomorphic vesicles, and make two symmetrical synapses per bouton, one onto a spine head and the other onto the underlying dendritic shaft. They are infrequent (0.2%), being found only in association with dendritic spines. Type 4 endings contain large pleomorphic synaptic vesicles and no dense-core vesicles. They make symmetrical contacts with the short primary dendrites. Type 5 endings contain a mixture of small clear pleomorphic vesicles and numerous large dense-core vesicles. They contact only the cell body and the short primary dendrites, making up 20% of somatic synaptic contacts but less than 1% of contacts onto dendrites. Type 6 boutons contain oval and flattened synaptic vesicles and establish symmetrical contacts with higher-order dendritic branches and the cell body.

Animals↗
PubMed1983

Bridge balance in intracellular recording; introduction of the phase-sensitive method.

Passing current through the microelectrode during intracellular recording produces an artifactual voltage-drop across the electrode's resistance. In modern biological amplifiers, the means of removing this artifact is through what is no more than an analog arithmetic unit which subtracts a voltage, having some fixed proportion to the current being injected, from the voltage appearing at the input to the amplifier. Various techniques have evolved for determining that fixed proportion, an operation which has come to be referred to as bridge balance, and these are reviewed. A new method is presented for determining bridge balance and another amplifier parameter which affects current injection, capacitance neutralization. Essentially, a sinusoidal current is passed through the electrode and preparation at a frequency high enough so that the cellular membrane presents negligable impedance but low enough so that the electrode appears as nearly a pure resistance. A set of analytical formulations is presented which describes the system and which is useful in choosing the best frequency of the test sinusoidal signal. This choice, part of the experimental design, is based on the predicted time constants of the recorded cell and the recording electrode. In using the phase-sensitive method, the capacitance neutralization of the recording amplifier is adjusted until there is no phase error in the injected current. Bridge balance can then be adjusted until no sinusoidal signal is visible at the output of the amplifier. Both bridge balance and correction of capacitance compensation can be automatically and continuously performed during intracellular recording by incorporating a phase-sensitive alternating current (AC) voltmeter (i.e. a lock-in amplifier) into the system. This permits accurate measurement of intracellular potential during current injection even though the resistance of the electrode might be changing.

Animals↗
PubMed1982

An intracellular HRP study of the rat globus pallidus. I. Responses and light microscopic analysis.

A study of the intracellularly recorded responses of rat globus pallidus neurons to activation of striopallidal fibers was combined with light microscopic examination of the morphology of these same neurons using intracellular horseradish peroxidase. The response to stimulation of caudate-putamen is an inhibitory postsynaptic potential with observed latencies ranging from 5.1 to 9.8 msec. These values correspond to conduction velocities of 0.4 to 0.8 m/second for striopallidal fibers. Comparison with extracellular controls shows no excitatory component to the response. All recovered and analyzed neurons (n = 11) were of the large type of pallidal neuron known from Golgi studies but the addition that two subtypes could be recognized. Large neurons located medially in the nucleus had dendritic fields with large dorsoventral extent (ca. 1 mm) when compared to their mediolateral and rostrocaudal dimensions (ca. 0.4 mm) and these neurons emitted no axon collaterals. Large neurons located laterally in the nucleus had disklike dendritic fields with both dorsoventral and rostrocaudal dimensions being on the order of 1 mm but with a minor axis of approximately 100 micrometers. The axons of these neurons possessed collaterals. As a consequence of their disk-shaped dendritic field, neurons belonging to the laterally placed subgroup and occupying the narrow (ca. 100 micrometers thick) striopallidal border zone known to receive a distinct input from neostriatum have dendrites restricted to that zone.

Afferent Pathways↗
PubMed1982

Serotonergic excitation from dorsal raphe stimulation recorded intracellularly from rat caudate-putamen.

Similar to other afferents to rat caudate-putamen, stimulation of the dorsal raphe nucleus evokes a series of 3 responses which can be recorded intracellularly. An initial depolarization is followed by a long-lasting inhibition which is, in turn, terminated by another period of depolarization. Pharmacological manipulations demonstrate that the initial depolarizing potential is serotonergic. Depletion of serotonin by means of prior treatment with para-chlorophenylalanine leads to a reduction in the amplitude of the depolarization which can be evoked by maximal stimulation of dorsal raphe. Neither the long-lasting hyperpolarization nor the late excitation which follow the initial depolarization is affected. Replacement of serotonin in levels by injection of 5-hydroxytryptophan results in a restoration of the amplitude of the depolarizing response. The latency of the initial depolarization is, however, unchanged in serotonin-depleted animals. This together with the observation in some cells of a component of the initial depolarization resistant to para-chlorophenylalanine treatment, suggests that there is a non-serotonergic excitation which precedes that mediated by serotonin.

5-Hydroxytryptophan↗
PubMed1982

Morphology and intracellular responses of an identified dorsal raphe projection neuron.

Stimulation of ventral medial tegmentum elicits an antidromic action potential and an inhibitory postsynaptic potential in dorsal raphe projection neurons. The inhibitory postsynaptic potential is not wholly due to activation of recurrent inhibitory circuits as it is not monosynaptic and its onset precedes the antidromic action potential. Light microscopic examination of horseradish peroxidase-filled projection neurons reveals a neuron type with radiating, poorly branched dendrites and terminal dendritic thickets. The axon of the exemplary neuron presented is seen to leave the nucleus but gives off a single collateral while still within the parent cell's dendritic domain.

Action Potentials↗
PubMed1981

Single electrode voltage clamp by iteration.

A technique for providing conditions of voltage clamp which differs considerably from other voltage clamp schemes has been developed. The feedback network which determines the current which will clamp the cell to the desired voltage does not operate in real time. Instead, the system uses a form of discontinuous feedback. The event to be clamped, which must be one which can be made to repeat itself without change, is elicited and allowed to run to completion without the intervention of feedback. During each repetition of the event, a current waveform is injected whose shape is based on the foregoing trials (iterations). Successive repetitions of this process develop a current waveform which ever more closely clamps the voltage to the desired value. Implementation involves a means of converting the intracellular voltage signal to digital form (a transient recorder), a means of processing the digitalized voltage signal (a digital computer), and a means of delivering the clamping current back to the preparation. The system has two advantages over other voltage clamp techniques. First, that the feedback loop is open in real time confers great stability. This advantage is exploited in the use of iterative voltage clamp in single electrode preparations. Secondly, iterative voltage clamp is essentially unlimited in the speed with which it can respond to transients. This would make the technique of interest even in preparations such as squid giant axon, where two electrodes are used and very fast responsiveness is desired.

Animals↗
PubMed1980

Recurrent inhibition in the rat neostriatum.

During intracellular recording, in the neostriatum of rats anesthetized with urethane, the triggering of an action potential in the recorded neuron by a depolarizing pulse of current resulted in inhibition in that same neuron. This inhibition was evident through its ability to reduce the amplitude of EPSPs evoked from stimulation of substantia nigra. The shunting of SN EPSPs was shown not to be due to action potential currents. The inhibition is antagonized by the GABA blocking agent bicuculline. Intracellular labeling of recorded neurons revealed them as medium spiny neurons. It is concluded that the extensive axon collaterals of spiny projection neurons mediate recurrent inhibition, a portion of which involves autaptic synapses of a neuron back onto itself.

Animals↗