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Biomedical subjects

M Segal

Publications and source records attributed to M Segal.

At least 235 records · Page 13Linked to original sources
PubMed1985

A potent transient outward current regulates excitability of dorsal raphe neurons.

Activity of neurons in the dorsal raphe nucleus of the rat was recorded intracellularly in a brainstem slice. The neurons had a high input resistance, a linear I-V curve in the hyperpolarizing direction and a long membrane time constant. Broad action potentials were followed by a large afterhyperpolarization (AHP). This AHP removes partial inactivation of a potent transient outward rectifier that is activated by a subsequent depolarization of the neuron; it clamps the cell membrane at a potential slightly below firing level and blocks generation of action potentials for up to 100 ms. The transient rectification was sensitive to 4-aminopyridine (4-AP) but not to tetraethylammonium (TEA). It appears to share similar properties with those of IA seen elsewhere and to function in the regulation of interspike intervals of dorsal raphe (DR) neurons in vitro.

4-Aminopyridine↗
PubMed1985

Transplanted septal neurons make viable cholinergic synapses with a host hippocampus.

Cell suspensions from the fetal septal region were injected stereotaxically into the hippocampus of fornix-fimbria-transected adult rats. The host rats were sacrificed up to 3 months after the operation and the hippocampus sliced into 350 microns transverse slices. Intracellular recording was made from CA1 neurons adjacent to the graft. Electrical stimulation of the graft produced a voltage-dependent depolarization in some recorded neurons. This was associated with an increase in spontaneous and anodal break action potential discharges. In addition, a slow after-hyperpolarization (AHP) which typically follows a burst discharge was blocked during the depolarization indicating that the stimulation may block a Ca2+-dependent K+ current. The effects of the stimulation were antagonized by atropine. A response to the stimulation was seen 2 weeks but not 1 week after grafting. Over time, cells that were located away from the graft became activated by the stimulation. This was correlated with the extent of proliferation of acetylcholinesterase-containing fibers around the graft. These results suggest that grafted septal neurons make viable cholinergic connections with a host hippocampus.

Acetylcholinesterase↗
PubMed1985

Impulse conduction properties of noradrenergic locus coeruleus axons projecting to monkey cerebrocortex.

Antidromically driven action potentials were recorded from norepinephrine-containing locus coeruleus neurons in response to electrical stimulation of cerebrocortical and thalamic areas in anesthetized squirrel monkeys. These cells reliably conducted impulses from cortical sites of distances up to 100 mm from locus coeruleus. Monkey locus coeruleus neurons were found to exhibit several properties previously described for these cells in rat, including slow spontaneous discharge rates, characteristic impulse waveforms, antidromic activation from many target areas, a period of suppressed activity following either antidromic or orthodromic driving and responsiveness to noxious stimuli presented as subcutaneous electrical stimulation of a rear foot. However, a large population of monkey locus coeruleus neurons was found to exhibit more rapid conduction velocities than previously found for rat (e.g. approximately 34% were greater than 1 m/s), resulting in similar conduction latencies to distant target areas in the two species. This indicates that the conduction times required for locus coeruleus impulses to reach distant target areas may be conserved across different species and sizes of brains, suggesting that these latencies play an important role in the general function of the locus coeruleus system in brain and behavioral processes.

Animals↗
PubMed1985

An electrophysiological study of neurones in the rat median raphe and their projections to septum and hippocampus.

Extracellular single unit recordings were made in the median raphe nucleus from rats anaesthetized with urethane. Spontaneous firing as well as orthodromic and antidromic responses to stimulation of the fornix and the medial septum were studied. One hundred and twelve units (out of a total of 355) with a regular spontaneous firing rate of 0.2-3 spikes/s were classified as serotonin-containing neurons. Fifty nine of them were antidromically invaded from either the fornix or the medial septum (conduction velocity, 0.8 m/s) and 7 additional neurones from both the fornix and the medial septum. Antidromic action potentials were followed by a period of decreased probability of firing, that was already present below threshold for antidromic invasion, were proportional to the stimulation intensity and had a latency similar to orthodromic inhibition. No preferential topographical distribution within the median raphe nucleus was observed for the serotonin neurones, even those invaded antidromically. Twenty six neurones with a clear-cut anatomical location around the borders of the median raphe nucleus showed a spontaneous rhythmic activity (4-20 spikes/s) characterized by the presence of extremely prolonged silent periods (up to 5 min). Only one of these neurones was invaded antidromically from the medial septum and none from the fornix. Of the remaining non-serotonin neurones, 28 showed a very low firing rate consisting of single action potentials every 10-60 s while 189 had a spontaneous activity of 6-30 spikes/s. Regardless of their firing rate they were all antidromically invaded from the fornix and/or the medial septum and had a conduction velocity of 5 m/s. These experiments demonstrate the electrophysiological heterogeneity of the neuronal population of the median raphe nucleus, the presence of strong projections of both putative serotonin and non-serotonin neurones to the medial septum and, via the fornix, to the hippocampus, and the existence of axonal branching in both types of neurones.

Animals↗
PubMed1985

Ontogeny and regional distribution of proenkephalin- and prodynorphin-derived peptides and opioid receptors in rat hippocampus.

Levels of prodynorphin- and proenkephalin-derived peptides were determined in whole hippocampus of prenatal and early postnatal rats and in five regions of the hippocampus of the adult rat. Using autoradiography, opioid receptor subtypes were localized in coronal sections of adult hippocampus. The opioid peptides are present in very low concentrations in prenatal hippocampus, with only dynorphin B and alpha-neo-endorphin being present in significant amounts. The main increase in concentrations of the opioid peptides occur between day 7 and 14 postnatally, when dynorphin A, dynorphin A-(1-8), dynorphin B and alpha-neo-endorphin reach their adult levels. beta-Neo-endorphin and [Met]enkephalyl-Arg-Gly-Leu do not reach their maximal level until later in development. There is a distinct differential distribution of the opioid peptides in the subregions of the hippocampus; the subiculum and CA1 are relatively poor in prodynorphin-derived peptides but do contain significant amounts of [Met]enkephalin and [Leu]enkephalin. Very high concentrations of dynorphin B and alpha-neo-endorphin are present in region CA4. Dynorphin A-(1-8) and [Met]enkephalin have their highest concentrations in the dentate gyrus. There is a 5-fold higher concentration of [Met]enkephalin in the ventral hippocampus compared to the dorsal hippocampus. A similar trend is seen with dynorphin A-(1-8) but not with the other opioid peptides. The most abundant opioid receptor population in the hippocampus is of the mu type and it is densest in and around stratum pyramidale of the region CA3. There are relatively few kappa opioid receptors in the rat hippocampus. These results indicate the presence of at least two independent opioid neuronal systems (enkephalin and dynorphin) in rat hippocampus and the presence of mu-, delta- and kappa-opioid receptor subtypes.

Aging↗
PubMed1985

Seasonal variation in the development of stress-induced systolic hypertension in the rat.

Seasonal variation in blood pressure in human hypertensives prompted us to investigate whether such a phenomenon also occurs in rats made hypertensive by environmental stress. Groups of eight to 20 rats, housed in stress chamber under natural light conditions at 21 +/- 1 degree C, were subjected to noise (85-105 dB) and light stress for 4 h three times per week for 16 weeks, over 4 years. Systolic pressure increased by 14-25 mmHg after 6-8 weeks of stress from October to January. Artificial environmental light for 15 h prevented development of hypertension by stress, which could also be reversed by acute administration of propranolol. Hypertensive rats had significantly greater relative heart and adrenal weights. This phenomenon can be explained by amplification of sympathetic pressor activity by stress hormones, adrenaline, corticosterone and prolactin, under the influence of melatonin.

Animals↗
PubMed1984

Primary ovarian carcinoid with marked heterogeneity of microscopic features.

A primary ovarian carcinoid tumor in a 54-year-old patient with the carcinoid syndrome is reported. On histologic examination there were, in addition to typical insular and atypical ribbon-like areas, solid and papillary growth patterns with pleomorphic and clear cells, some with anaplastic features. The heterogeneity seen in this case has not been reported in an ovarian carcinoid. However, since argentaffine and some argyrophil granules were demonstrated by special stains and ultrastructural studies in all of the various cellular elements, it was concluded that the entire tumor represented a carcinoid. This case demonstrates that ovarian carcinoids are not necessarily insular, trabecular, or mixtures thereof, but can also be extremely heterogeneous. In order to identify more tumors of this kind and also to avoid a diagnosis of an anaplastic or unclassifiable carcinoma in such cases, it is recommended that special stains for neurosecretory granules and electron microscopic examination be carried out in a larger number of poorly differentiated ovarian neoplasms, especially in those in which some of the microscopic features are suggestive of a carcinoid.

Carcinoid Tumor↗
PubMed1984

GABA actions on the excitability of cultured CNS neurons.

The membrane mechanisms associated with Cl- conductance activated by GABA in spinal and hippocampal neurons cultured from the embryonic mouse and rat have been studied with voltage- and patch-clamp techniques. The elementary mechanism underlying the conductance response is predominantly all-or-none with both similar and different kinetics in different assays. beta-Alanine and glycine also alter conductance via a similar mechanism, but the electrical properties associated with each transmitter are unique. Clinically important drugs modulate GABA-mediated responses by altering the kinetics of ion channel activity. Inhibitory synaptic currents whose time constant of decay coincides with the common, slower phase of channel kinetics in pharmacological experiments are altered in amplitude and/or time course by the same drugs. The results strongly suggest that the synaptic events reflect the activation of 1700 channels whose open-time distribution describes the time constant of decay.

Animals↗
PubMed1984

Phenylethylamine, norepinephrine and mounting behavior in the male rat.

Phenylethylamine, which induces mounting behavior in naive adult male rats when administered chronically, was shown to selectively raise brain norepinephrine levels in the medial preoptic nucleus, a region known to be implicated in the regulation of sexual behaviors. It is suggested that the catecholamine alteration is a secondary response to the primary influence of phenylethylamine on the preoptic nucleus.

Animals↗
PubMed1984

Rat hippocampal neurons in culture: properties of GABA-activated Cl- ion conductance.

The actions of gamma-aminobutyric acid (GABA) on the membrane properties of rat hippocampal neurons maintained in dissociated cell culture were studied using intracellular recording techniques. All the neurons tested were responsive to GABA applied by pressure from micropipettes containing 10-20 microM GABA. The response consisted of a marked increase in conductance associated with a potential change. The inversion potential was sensitive to the Cl- ion gradient across the cells. It was about -60 mV when measured during recordings utilizing K acetate-filled microelectrodes, about -15 mV when measured during recordings with KCl-filled microelectrodes, and about +15 mV when measured with KCl electrodes in a medium containing low [Cl-]o. These results indicate that the membrane conductance evoked by GABA primarily involves Cl- ions. There were no apparent differences between the inversion potential of responses elicited at the level of the cell body and those evoked on processes. The two-electrode voltage-clamp technique was used to study the membrane mechanisms underlying these responses. GABA generated current responses that were associated with an increase in both conductance and membrane current variance. At a given potential both the conductance change and increase in variance were directly proportional to the amplitude of the current response. Spectral analysis of the membrane current variance evoked by GABA revealed that many of the computed spectra could be fitted by a single Lorentzian equation, suggesting that GABA activates two-state (open-closed) Cl- ion channels whose durations are exponentially distributed. The mean duration of these channel openings was estimated to be 22.9 +/- 2.1 ms, while the average conductance was estimated to be 19.8 +/- 2.7 pS in 13 cells. Large-amplitude GABA responses evoked at -70 mV frequently faded in amplitude, often by as much as 50%, with little or no change in the associated conductance. Since the membrane current variance decreased in direct relation to the fading current response, while estimates of channel lifetime did not change, the results suggest that the fading is due to a shift in the Cl- gradient. Responses to constant amounts of GABA evoked at different membrane potentials showed that the macroscopic conductance activated by GABA varied with membrane potential. Often 4-5 times more conductance was generated at depolarized (0 to +10 mV) relative to hyperpolarized potentials (-60 to -70 mV).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Rat hippocampal neurons in culture: potassium conductances.

Two-electrode voltage-clamp methodology was used to analyze voltage-dependent ionic conductances in 81 rat hippocampal neurons grown in culture for 4-6 wk. Pyramidal and multipolar cells with 15- to 20-micron-diameter cell bodies were impaled with two independent KCl electrodes. The cells had resting potentials of -30 to -60 mV and an average input resistance of about 30 M omega. A depolarizing command applied to a cell maintained in normal medium invariably evoked a fast (2-10 ms) inward current that saturated the current-passing capacity of the system. This was blocked in a reversible manner by application of tetrodotoxin (TTX) (0.1-1.0 microM) near the recorded cell. In the presence of TTX, a depolarizing command evoked a rapidly rising (3-5 ms), rapidly decaying (25 ms) transient outward current reminiscent of "IA" reported in molluscan neurons. This was followed by a more slowly activating (approximately 100 ms) outward current response of greater amplitude that decayed with a time constant of about 2-3 s. These properties resemble those associated with the K+ conductance, IK, underlying delayed rectification described in many excitable membranes. IK was blocked by extracellular application of tetraethylammonium (TEA) but was insensitive to 4-aminopyridine (4-AP) at concentrations that effectively eliminated IA. IA, in turn, was only marginally depressed by TEA. Unlike IK, IA was completely inactivated when the membrane was held at potentials positive to -50 mV. Inactivation was completely removed by conditioning hyperpolarization at -90 mV. A brief hyperpolarizing pulse (10 ms) was sufficient to remove 95% of the inactivation. IA activated on commands to potentials more positive than -50 mV. The inversion potential of the ionic conductance underlying IA and IK was in the range of the K+ equilibrium potential, EK, as measured by the inversion of tail currents; and this potential was shifted in a depolarizing direction by elevated [K+]0. Thus, both current species reflect activation of membrane conductance to K+ ions. Hyperpolarizing commands from resting potentials revealed a time- and voltage-dependent slowly developing inward current in the majority of cells studied. This membrane current was observed in cells exhibiting "anomalous rectification" and was therefore labeled IAR. It was activated at potentials negative to -70 mV with a time constant of 100-200 ms and was not inactivated. A return to resting potential revealed a tail current that disappeared at about EK. IAR was blocked by extracellular CS+ and was enhanced by elevating [K+]0. It thus appears to be carried by inward movement of K+ ions.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Aminopyridine↗