Biomedical subjects

S B Khalsa

Publications and source records attributed to S B Khalsa.

24 records · Page 2Linked to original sources

PubMed1990

Calcium in phase control of the Bulla circadian pacemaker.

The circadian pacemaker in the retina of the eye of the marine snail Bulla gouldiana was examined using the whole eye in vitro preparation. Phase-response curves were generated to 6-h pulses of a low calcium EGTA solution and to a hyperpolarizing low potassium-low sodium solution. Both treatments yielded similar phase response curves with phages delays in the late subjective night/early subjective day and phase advances in the late subjective day. The similarity of the phase response curves to hyperpolarizing and low calcium solutions and the absence of additivity when both treatments are combined raises the possibility that both treatments affect the underlying pacemaker through a common mechanism. The persistence of phase shifts to low calcium pulses delivered in the presence of depolarizing light suggests that hyperpolarization is not required for low calcium phase shifting. However, it is possible that both treatments act by reducing a transmembrane calcium flux which is postulated to result from the periodic depolarization of the pacemaker cell membrane during the subjective day. Since a transmembrane calcium flux is known to be essential for both light and depolarization-induced phase shifting, we discuss the hypothesis that calcium fluxes play a pivotal role in the entrainment pathway of the circadian pacemaker.

Action Potentials↗

PubMed1988

Calcium channels mediate phase shifts of the Bulla circadian pacemaker.

1. Light-induced phase advances of the activity rhythm of the Bulla ocular circadian pacemaker are blocked when the extracellular calcium concentration is reduced with EGTA to 0.13 microM. Phase advances are also blocked in low calcium solutions without EGTA [( Ca] less than 50 microM). 2. The dependence of light-induced phase delays on extracellular calcium concentration in EGTA-free seawater was determined. Phase delays are blocked at calcium concentrations below 400 microM, and reduced at concentrations of 1 mM and 3.5 mM (relative to shifts in normal ASW, [Ca] = 10 mM). Phase delays are also reduced and blocked at calcium concentrations higher than normal (60 mM and 110 mM, respectively). 3. Low calcium EGTA also blocked both phase delays and phase advances induced by pulses of depolarizing high K+ seawater. Low calcium EGTA pulses presented alone at the same times did not generate significant phase shifts. 4. The organic calcium channel antagonists verapamil, diltiazem and nitrendipine as well as the inorganic calcium channel antagonists La3+, Co2+, Cd2+, and Mn2+ were applied along with light pulses, however, the treated eyes were either phase shifted by these substances, or these substances were found to be toxic. 5. The inorganic calcium channel antagonist Ni2+ blocked both light-induced phase delays and advances at a concentration of 5 mM. Ni2+ applied alone did not generate significant phase shifts. Phase delays induced by high K+ seawater were blocked in the presence of 50 mM Ni2+ but not in 5 mM Ni2+. The light-induced CAP activity of the putative pacemaker cells was not inhibited by Ni2+, suggesting that its blocking action was probably via its known role as a calcium channel antagonist.

Action Potentials↗

PubMed1988

Phase-shifts of the Bulla ocular circadian pacemaker in the presence of calmodulin antagonists.

Previous work has shown that light-induced phase shifts of the Bulla ocular circadian pacemaker require extracellular calcium, suggesting the possibility that the action of calcium as a second messenger via calmodulin is an element in the phase shifting mechanism. The calmodulin antagonists calmidazolium, trifluoperazine (TFP) and W7 were applied with phase shifting light pulses. Light phase shifts were not blocked by calmidazolium or TFP, suggesting that calmodulin does not mediate light-induced phase shifts. Period changes were observed with treatments of both TFP and W7, but not with calmidazolium and are probably not calmodulin-mediated.

Animals↗

PubMed1987

Vestibular nuclear neuron activity during active and passive head movement in the alert rhesus monkey.

Responses of single neurons were recorded in the medial and descending vestibular nuclei (MVN and DVN) and in the deep cerebellar nuclei of three juvenile rhesus monkeys (Macaca mulatta). Neuronal activity was measured during both passive sinusoidal and nonsinusoidal whole body rotation (peak velocities were under 90 degrees/s) and during active head movements. Although the active head movements occasionally exceeded 300 degrees/s, most exhibited peak velocities of less than 200 degrees/s. A total of 133 units sensitive to horizontal head rotation were recorded, and of these, 38 were held for sufficient time to obtain both passive and active head movement data. Comparison of the neuronal firing patterns obtained during active and passive head movements revealed no apparent differences. Thus neurons that were observed to burst or pause during saccades with the head fixed continued to do so when the head was free. Both the sensitivity to head velocity and the "inferred" spontaneous firing rate were compared during active and passive head movements by plotting rate-velocity curves for both conditions. When the data points were fitted with linear regression lines, no statistically significant differences in either sensitivity or spontaneous rate were found. The present study provides no evidence that efferent vestibular activity alters the properties of afferent vestibular neurons during active head movements, as has previously been suggested (21). Furthermore, neurons in the rostral portions of the vestibular nuclei in primates encode head velocity based entirely on labyrinthine information. Neither neck proprioceptors nor an efference copy of the head movement motor program seem to contribute significantly to the firing patterns observed.

Animals↗

PubMedDate not supplied

Circadian rhythms.

Circadian rhythms are a ubiquitous adaptation of eukaryotic organisms to the most reliable and predictable of environmental changes, the daily cycles of light and temperature. Prominent daily rhythms in behavior, physiology, hormone levels and biochemistry (including gene expression) are not merely responses to these environmental cycles, however, but embody the organism's ability to keep and tell time. At the core of circadian systems is a mysterious mechanism, located in the brain (actually the suprachiasmatic nucleus of the hypothalamus) of mammals, but present even in unicellular organisms, that functions as a clock. This clock drives circadian rhythms. It is independent of, but remains responsive to, environmental cycles (especially light). The interest in temporal regulation--its organization, mechanism and consequences--unites investigators in diverse disciplines studying otherwise disparate systems. This diversity is reflected in the brief reviews that summarize the presentations at a meeting on circadian rhythms held in New York City on October 31, 1992. The meeting was sponsored by the Fondation pour l'Etude du Système Nerveux (FESN) and followed a larger meeting held 18 months earlier in Geneva, whose proceedings have been published (M. Zatz (Ed.), Report of the Ninth FESN Study Group on 'Circadian Rhythms', Discussions in Neuroscience, Vol. VIII, Nos. 2 + 3, Elsevier, Amsterdam, 1992). Some speakers described progress made in the interim, while others addressed aspects of the field not previously covered.

Aging↗

PubMedDate not supplied

Secondary vestibular and neck position signals in the vestibular nuclei of alert rhesus monkeys performing active head movements.

Rhesus monkeys were trained to track a visual target with head and eye movements in order to study central vestibular neurons under natural conditions. Single unit recordings of cells in the vestibular nuclei were obtained during active head rotations in the horizontal plane, and also during passive copies of these self-induced movements. Most cells exhibited secondary responses immediately following the primary vestibular responses to active or passive rapid head movements. They were of opposite polarity to the primary responses, and generally rate enhancements of secondary responses were of greater amplitude than rate suppressions. In addition, vestibular nuclei cells also encoded tonic neck position. The corresponding signal consisted of a variation in the basal discharge rate as a function of neck, and thus head, position. These observations prove for the first time that dynamic and static response characteristics recorded earlier from lesioned brains and under anaesthesia are, at least qualitatively, representative for the normally behaving vestibulomotor system in primates.

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