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S L Cochran

Publications and source records attributed to S L Cochran.

At least 19 recordsLinked to original sources
PubMed1995

Functional support of glutamate as a vestibular hair cell transmitter in an amniote.

Although hair cells in the cochlea and in the vestibular endorgans of anamniotes are thought to release glutamate or a similar compound as their transmitter, there is little evidence in amniotes (which, unlike anamniotes, possess both type I and II hair cells) as to the nature of the hair cell transmitters in the vestibular labyrinth. We have recorded extracellularly from single semicircular canal afferents in the turtle labyrinth maintained in vitro and have bath-applied a number of transmitter agonists and antagonists to relate the effects of these substances to the actions of the endogenous transmitter substances. Both glutamate and aspartate strongly excite the afferents while GABA and carbachol have negligible or weak effects. In contrast to its lack of effect on afferent activity in some anamniotes, N-methyl-D-aspartate (NMDA) was also found to excite these afferents. Kynurenic acid reversibly reduced the resting firing rates of the afferents and the increases in firing due to the application of glutamate and aspartate. These findings provide preliminary support for the hypothesis that glutamate (or a related compound) is also a vestibular hair cell transmitter in amniotes.

Action Potentials↗
PubMed1995

Cationic influences upon synaptic transmission at the hair cell-afferent fiber synapse of the frog.

The concentrations of inorganic cations (K+, Na+, and Ca2+) bathing the isolated frog labyrinth were varied in order to assess their role in influencing and mediating synaptic transmission at the hair cell-afferent fiber synapse. Experiments employed intracellular recordings of synaptic activity from VIIIth nerve afferents. Recordings were digitized continuously at 50 kHz, and excitatory postsynaptic potentials were detected and parameters quantified by computer algorithms. Particular attention was focused on cationic effects upon excitatory postsynaptic potential frequency of occurrence and excitatory postsynaptic potential amplitude, in order to discriminate between pre- and postsynaptic actions. Because the small size of afferents preclude long term stable recordings, alterations in cationic concentrations were applied transiently and their peak effects on synaptic activity were assessed. Increases in extracellular K+ concentration of a few millimolar produced a large increase in the frequency of occurrence of excitatory postsynaptic potentials with little change in amplitude, indicating that release of transmitter from the hair cell is tightly coupled to its membrane potential. Increasing extracellular Na+ concentration resulted in an increase in excitatory postsynaptic potential amplitude with no significant change in excitatory postsynaptic potential frequency of occurrence, suggesting that the transmitter-gated subsynaptic channel conducts Na+ ions. Decreases in extracellular Ca2+ concentration had little effect upon excitatory postsynaptic potential frequency, but increased excitatory postsynaptic potential frequency and amplitude. These findings suggest that at higher concentrations Ca2+ act presynaptically to prevent transmitter release and postsynaptically to prevent Na+ influx during the generation of the excitatory postsynaptic potential. The influences of these ions on synaptic activity at this synapse are remarkably similar to those reported at the vertebrate neuromuscular junction. The major differences between these two synapses are the neurotransmitters and the higher resting release rate and higher sensitivity of release to increased K+ concentrations of the hair cells over that of motor nerve terminals. These differences reflect the functional roles of the two synapses: the motor nerve terminal response in an all-or-nothing signal consequent from action potential invasion, while the hair cell releases transmitter in a graded fashion, proportionate to the extent of stereocilial deflection. Despite these differences between the two junctions, the similar actions of these elemental cations upon synaptic function at each implies that these ions may participate similarly in the operations of other synapses, independent of the neurotransmitter type.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Evidence against a hypothesis of vestibular efferent function.

Efferent stimulation and nicotinic agonists can either decrease or increase the frequency of occurrence of EPSPs recorded from VIIIth nerve afferents in the frog. It has been hypothesized that the distribution of hair cell resting membrane potentials overlaps the equilibrium potential dictated by the nicotinic-gated channels on the hair cells. Nicotinic mediated increases in EPSP frequency would then be due to depolarization of hair cells that were more hyperpolarized at rest, while decreases in EPSP frequency would be due to hyperpolarization of hair cells more depolarized at rest. In order to test this hypothesis, while recording from afferents which showed an increase in EPSP frequency due to bath application of the nicotinic agonist DMPP (1,1-dimethyl-4-phenylpiperizinium iodide), hair cells were depolarized with 10 mM K+ in the bath, and then the effects of DMPP on EPSP frequency were assessed. In this situation, DMPP still increased EPSP frequency, suggesting that the equilibrium potential for the nicotinic-gated channel was much more positive than the resting potentials of the hair cells. An alternative hypothesis then seems likely, that the nicotinic receptors on hair cells are able to activate different iontophores that result in either hair cell depolarization or hyperpolarization, dependent upon which iontophore predominates in the hair cells innervating a particular afferent.

Afferent Pathways↗
PubMed1993

Algorithms for detection and measurement of spontaneous events.

The development of the personal computer and its mass storage capabilities has enabled long-term digitization of voltage records at high sampling rates. This paper presents a program that employs algorithms to analyze a sampled record for spontaneously occurring events. A detection algorithm employs amplitude and temporal parameters to identify the onsets of these events. Other algorithms then characterize size and shape features of these events. Examples of the results of these algorithms are given for intracellularly recorded excitatory postsynaptic potentials (EPSPs). These algorithms permit rapid and accurate quantitation of tens of thousands of events that may occur over many minutes. It is suggested that this set of algorithms may be applied to biological events other than synaptic potentials.

Algorithms↗
PubMed1992

Granulosa-theca cell tumor associated with an ovulation fossa and normal ovarian stroma in a mare.

A granulosa-theca cell tumor was found in an ovary that had an ovulation fossa and normal ovarian tissue. The ovary was removed from a mare with a history of ovarian enlargement and behavioral changes. The affected ovary had a multicystic appearance on ultrasonographic examination performed before surgery, and an ovulation fossa was not palpable on examination per rectum. However, during surgery, the affected ovary was found to be within normal size limits, with an enlargement on 1 pole, and to contain an ovulation fossa. Atrophy of the infundibulum of the affected ovary helped to confirm the diagnosis of granulosa-theca cell tumor, and the ovary was removed. The mare's testosterone concentrations were normal. Granulosa-theca cell tumors are usually associated with a spherical ovary, attributable to ablation of the ovulation fossa, with no normal ovarian tissue present.

Animals↗
PubMed1990

Synapsin I injected presynaptically into goldfish mauthner axons reduces quantal synaptic transmission.

1. Synapsin I was injected into a vertebrate presynaptic axon to analyze its action on quantal synaptic transmission. Two microelectrodes were used for simultaneous intracellular recording from pairs of identified neurons in the goldfish brain. The postsynaptic electrode was placed in a cranial relay neuron (CRN) within 100 microns of its synapse with the Mauthner neuron. The presynaptic electrode impaled the Mauthner axon (M-axon) 50-200 microns from the first electrode. 2. Spontaneous miniature excitatory postsynaptic potentials (mEPSPs) and evoked postsynaptic potentials (EPSPs) were recorded at steady states before and after synapsin I was microinjected into the presynaptic M-axon. Responses were digitized and subsequently analyzed by computer for quantal parameters. 3. In 12 experiments, injection of synapsin I resulted in a reduction in transmission. The decrease in EPSP amplitude began approximately 30 s after the injection, reached a plateau within 10 min, and appeared to be reversible and dose dependent. 4. Injection of synapsin I decreased quantal content (m), with no effect on postsynaptic receptor sensitivity or on amount of transmitter per quantum. Further analysis based on the simplest binomial model for quantal release revealed that synapsin I consistently reduced the number of quantal units available for release (n) although the probability of release (p) was either unchanged or slightly increased. Injected synapsin I may thus bind to presynaptic vesicles and prevent transmitter quanta from entering a pool subject to evoked release.

Animals↗
PubMed1989

Quantal transmission at Mauthner axon target synapses in the goldfish brainstem.

The Mauthner axon contacts two principal neurons within the brainstem: the cranial relay neuron and the follower neuron. The cranial relay neuron is excited through axoaxonic contacts by both Mauthner axons, while the follower neuron is excited by the Mauthner axon ipsilateral to its soma and inhibited (through an interposed neuron) by the contralateral Mauthner axon. We have investigated the properties of these two Mauthner axon target synapses with simultaneous pre and postsynaptic recordings in order to determine if transmission can be described in terms of the quantal hypothesis and to determine what quantal parameters change with alterations in the frequency of Mauthner cell activation. Small depolarizing postsynaptic potentials, recorded in the cranial relay neurons, increase their frequency of occurrence when depolarizing currents are applied to the Mauthner axon, without changing their mean amplitude, indicating that they arise from the Mauthner axon terminal and represent quantal units of the evoked cranial relay neuron excitatory postsynaptic potentials. Similar small, spontaneous potentials can also be recorded from the follower neurons. Amplitude histograms of evoked postsynaptic potentials (in both cranial relay neurons and follower neurons) can be fit by binomial models based on the amplitude and variance of the spontaneous potentials, suggesting that the quantal hypothesis is a valid descriptor of synaptic transmission at these contacts. Quantal content ("m"), the number of releasable quanta ("n"), and the probability of release ("p") are relatively high for both the cranial relay neurons and follower neurons. Increasing the frequency of Mauthner axon stimulation results in a decrement in the postsynaptic potential amplitude in both target cells. There is no change in the amplitude of the small, spontaneous potentials (measured during the stimulation period) with stimulus frequency, indicating a decrease in quantal content, but not quantal size. The change in quantal content is explained in binomial terms by a decrease in the number of releasable quanta, but not the probability of release in both the cranial relay neurons and the follower neurons. These findings suggest that the supply of transmitter available to be released decreases with increasing stimulus frequency without affecting the nerve terminal's ability to release transmitter (at these stimulus frequencies). Synaptic vesicles, observed in clusters in the terminals at the ultrastructural level, may be a physical correlate of the binomial parameter ("n"). It is predicted that the decrease in the binomial parameter ("n") with increasing frequency of stimulation is accompanied by a decrease in the number of active zones occupied by vesicles.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1987

Pharmacological aspects of excitatory synaptic transmission to second-order vestibular neurons in the frog.

Synaptic excitation of second-order vestibular neurons is mediated by two principal afferents: vestibular afferents projecting into the brain via the VIIIth cranial nerve and commissural afferents from the contralateral vestibular nuclear complex. The shape of the excitatory postsynaptic potentials (EPSPs) generated by selectively activating these two inputs differs qualitatively, such that ipsilateral VIIIth nerve afferents generate a faster-rising EPSP than do the commissural afferents. We have investigated the synaptic pharmacology of these two inputs in the isolated, intact medulla of the frog in order to determine the nature of the transmitter substances released by the afferents and the nature of the subsynaptic receptors with which these transmitters interact. Electrical stimulation of the ipsilateral VIIIth cranial nerve evokes in the region of the vestibular nuclear complex a field potential that exhibits a presynaptic (afferent volley) and a postsynaptic (slow negativity) component. Bath application of glutamate receptor antagonists, such as kynurenic acid (KENYA), blocks the postsynaptic component of this field potential in a dose-dependent manner, without affecting the presynaptic volley, suggesting that the VIIIth nerve afferent releases glutamate and/or similar substances as its neurotransmitter. A comparison of the actions of various glutamate receptor antagonists to block this postsynaptic negativity gives a rank order of effectiveness such that KENYA greater than gamma-D-glutamylglycine (gamma DGG) = gamma-D-glutamylaminomethylsulfonic acid (GAMS) greater than gamma-D-glutamyltaurine (gamma DGT) much greater than gamma-D-glutamylaminomethylphosphonic acid (GAMP) greater than D-2-amino-5-phosphonovaleric acid (D-APV) greater than D,L-APV greater than D-2-amino-7-phosphonoheptanoic acid (APH). This rank order of effectiveness suggests that the VIIIth nerve transmitter activates second-order neurons through kainate (KA)/quisqualate (QUIS) synaptic receptors. Intracellular studies support these conclusions. Chemically mediated EPSPs evoked from ipsilateral VIIIth nerve stimulation are completely blocked by high concentrations of KENYA (greater than or equal to 1 mM). Occasionally an extremely short-latency, probably electrically mediated, component to these EPSPs persists in the presence of KENYA. The slower-rising EPSPs evoked from contralateral VIIIth nerve or contralateral vestibular nuclear complex stimulation are also completely blocked by KENYA, suggesting that the transmitter released by the commissural afferents is also glutamate and/or related compounds.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Evidence for an alteration in brainstem cholinergic pathways following unilateral labyrinthectomy in the frog.

Following VIIIth nerve stimulation, field potentials recorded in the contralateral vestibular nuclei of isolated medullae are larger in amplitude and more sensitive to atropine in chronically hemilabyrinthectomized frogs than those of controls. The atropine-sensitive component occurs at a latency which precludes involvement of the monosynaptic commissural projection between second order vestibular neurons. Therefore, in addition to this commissural projection, the contributions of more indirect pathways have to be considered in an attempt to understand the neuronal basis of behavioral improvement following vestibular lesions.

Animals↗
PubMed1985

Presynaptic actions of cholinergic agents upon the hair cell-afferent fiber synapse in the vestibular labyrinth of the frog.

Spontaneous activity of semicircular canal afferents in the isolated labyrinth of the frog is altered by bath application of cholinergic agonists. Muscarinic agonists can produce an increase in action potential frequency of individual afferents. This increase develops slowly and is prolonged in the time course of its action. Nicotinic agonists can either increase (most cases) or decrease afferent activity. These effects occur rapidly and decay during the period of activation, suggesting desensitization. Muscarinic effects are blocked by prior administration of atropine and nicotinic effects (both increases and decreases in action potential frequency) by curare. Intracellular recordings reveal that the nicotinic effects on afferent action potential frequency are the result of alterations in the frequency of spontaneous synaptic potentials, indicating a presynaptic site of action on the hair cells for these compounds. This conclusion is supported by the fact that in the presence of high Mg2+/low Ca2+, which blocks hair cell release of transmitter, cholinergic agonists do not affect the resting membrane potential of the vestibular afferent. Electrical stimulation of the VIIIth cranial nerve can result in either an increase or a decrease in spontaneous synaptic potential and action potential frequency of an afferent. These effects are blocked by prior administration of curare or of nicotinic agonists. Repetitive or continuous stimulation of the VIIIth nerve results in a reversible reduction of the evoked response, suggesting desensitization. Transection of the VIIIth cranial nerve two weeks prior to recording eliminates these actions of electrical stimulation, but not the responses to cholinergic agonists, indicating that the effects of electrical stimulation are mediated by centrally arising efferents. These findings confirm that acetylcholine is probably the transmitter released from centrally arising vestibular efferents, and, in addition, demonstrate that efferent-mediated effects are predominantly expressed through nicotinic receptors. Studies comparing the effects of isolation of the semicircular canal alone versus the intact labyrinth suggest that the method of isolation may be an important factor in determining whether efferent activity results in a predominant increase or decrease in afferent activity.

Acetylcholine↗
PubMed1984

Basic optokinetic-ocular reflex pathways in the frog.

Frogs (Rana temporaria) have two midbrain nuclei that receive contralateral retinal afferents, and whose neurons respond to optokinetic stimulation. The basal optic nucleus is composed of direction-selective neurons with different response types. One type is activated exclusively by upward moving optokinetic targets; another type is activated only by downward moving targets. Two other types of basal optic neurons show this vertical preference, but each is also activated by patterns moved horizontally from the nasal to temporal visual field. No activation of these cells was found with patterns moved horizontally from the temporal to nasal visual fields. Rather, cells in a discrete pretectal region have this type of sensitivity: they increase their resting rate with temporal to nasal stimulation and decrease it with nasotemporal stimulation. Oculomotor neurons (antidromically identified) have similar optokinetic sensitivities. As with basal optic neurons, these cells have exclusively upward or downward sensitivity, and some also have nasotemporal sensitivity. An additional type of oculomotor neuron and abducens motoneurons are activated by temporonasal pattern movement. In general, the extraocular motoneurons have similar velocity and pattern size preferences, as have the sensory nuclei. Investigations of the connectivity between the sensory and motor nuclei were primarily restricted to the relation between the pretectum and the abducens. A monosynaptic connection between the pretectum and the abducens is suggested by four points: (1) excitatory postsynaptic potential onset latency in antidromically identified abducens motoneurons, following optic nerve stimulation, is consistent with the interpretation of a disynaptic pathway to the abducens from the retina; (2) pretectal cells, sensitive to optokinetic stimulation, can be activated antidromically from stimulation of the abducens nucleus; (3) horseradish peroxidase injections into the pretectum result in labeling of axons, which terminate in the abducens nucleus; (4) horseradish peroxidase injections into the abducens result in labeling of cells in the pretectal region, where optokinetically sensitive cells are found. In the frog, there seem to be three-neuronal retino-ocular reflexes mediating optokinetic slow phase behavior as there are three-neuronal vestibulo-ocular reflexes that also mediate compensatory spatial behavior. It is suggested that these direct connections act to initiate ocular movements and accelerate the eye, whereas more indirect pathways may act to maintain eye position.

Afferent Pathways↗
PubMed1984

Pharmacology of the vestibular hair cell-afferent fiber synapse in the frog.

The isolated, intact, membranous labyrinth of the frog (Rana temporaria) has been investigated electrophysiologically in vitro to determine the nature of the transmitter substance at the synapse between the vestibular hair cells and afferent fibers. Spontaneous synaptic activity can be monitored with intra-axonal recordings from the afferents. Increased K+ in the bath results in an increase in frequency of presynaptic release, as indicated by an increased frequency of spontaneous synaptic potentials. Adding Mg2+ and lowering Ca2+ results in a decrease in synaptic potential frequency (often to zero) with no change in their mean amplitude, indicating pre-synaptic blockade. Extracellular recordings from individual vestibular afferents indicate that bath-applied glutamate and related acidic amino acids consistently increase the firing rates of these afferents in a dose-dependent manner with no evidence of desensitization. In the presence of presynaptic blockade (high Mg2+/low Ca2+), bath application of glutamate and its agonists results in a reversible depolarization of vestibular afferents, suggesting a postsynaptic action of these substances. 2-Amino-5-phosphonovaleric acid, kynurenic acid, and other acidic amino acid antagonists reversibly decrease the amplitudes of spontaneously occurring synaptic potentials without affecting their frequency, indicating subsynaptic blockade. These antagonists also block the postsynaptic depolarizations due to glutamate and its agonists. GABA and its agonists and antagonists have no consistent effect upon afferent activity. These findings suggest that glutamate, aspartate, or a related compound is the transmitter at this synapse. However, the antagonists used, or the receptors themselves, are not selective enough to discriminate adequately between the agonists. Therefore, which of these glutamate agonists are actually involved in synaptic transmission remains to be determined.

Afferent Pathways↗