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G S Bhumbra

Publications and source records attributed to G S Bhumbra.

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Spike coding during osmotic stimulation of the rat supraoptic nucleus.

Novel measures of coding based on interspike intervals were used to characterize the responses of supraoptic cells to osmotic stimulation. Infusion of hypertonic NaCl in vivo increased the firing rate of continuous (putative oxytocin) cells (Wilcoxon z= 3.84, P= 0.001) and phasic (putative vasopressin) cells (z= 2.14, P= 0.032). The irregularity of activity, quantified by the log interval entropy, was decreased for continuous (Student's t= 3.06, P= 0.003) but not phasic cells (t= 1.34, P= 0.181). For continuous cells, the increase in frequency and decrease in entropy was significantly greater (t= 2.61, P= 0.036 and t= 3.06, P= 0.007, respectively) than for phasic cells. Spike patterning, quantified using the mutual information between intervals, was decreased for phasic (z=-2.64, P= 0.008) but not continuous cells (z=-1.14, P= 0.256). Although continuous cells showed similar osmotic responses to mannitol infusion, phasic cells showed differences: spike frequency decreased (z=-3.70, P < 0.001) and entropy increased (t=-3.41, P < 0.001). Considering both cell types together, osmotic stimulation in vitro using 40 mm NaCl had little effect on firing rate (z=-0.319, P= 0.750), but increased both entropy (t= 2.75, P= 0.010) and mutual information (z=-2.73, P= 0.006) in contrast to the decreases (t= 2.92, P= 0.004 and z=-2.40, P= 0.017) seen in vivo. Responses to less severe osmotic stimulation with NaCl or mannitol were not significant. Potassium-induced depolarization in vitro increased firing rate (r= 0.195, P= 0.034), but the correlation with decreased entropy was not significant (r=-0.097, P= 0.412). Intracellular recordings showed a small depolarization and decrease in input resistance during osmotic stimulation with NaCl or mannitol, and membrane depolarization following addition of potassium. Differences in responses of oxytocin and vasopressin cells in vivo, suggest differences in the balance between the synaptic and membrane properties involved in coding their osmotic responses. The osmotic responses in vivo constrasted with those seen in vitro, which suggests that, in vivo, they depend on extrinsic circuitry. Differences in responses to osmolality and direct depolarization in vitro indicate that the mechanism of osmoresponsiveness within a physiological range is unlikely to be fully explained by depolarization.

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Rhythmic changes in spike coding in the rat suprachiasmatic nucleus.

The suprachiasmatic nucleus is regarded as the main mammalian circadian pacemaker but evidence for rhythmic firing of single units in vivo has been obtained only recently. The present study was undertaken to determine if rhythms could be seen using measures of activity in addition to the mean spike frequency. We investigated whether there were changes in the irregularity of cell activity measured by the disorder of the interspike interval distribution for neurones recorded in vivo and in vitro. By plotting the entropy of the log interval histogram that quantifies the coding capacity for each action potential against the respective zeitgeber time, we describe oscillations of spike activity in vivo. Entropy measures have the advantage over variances in that they quantify aspects of the shape of the distribution and not just the dispersion. One hundred and sixty-six cell recordings from the suprachiasmatic nucleus showed a significant rhythm in entropy with an oscillatory trend in the data (P < 0.001) showing a trough towards the end of the light period and a peak in the mid-dark period. There was a similar rhythm for the cells recorded from the peripheral zone (n = 209, P = 0.037). In separate experiments in vitro, to investigate the relationship between mean spike frequency and entropy, potassium-induced depolarization of cells recorded during the subjective night was correlated with a significant increase in mean spike frequency (r = 0.259, P = 0.011) and a decrease in entropy (r = -0.296, P = 0.004). The negative correlation between the entropy and mean spike frequency of cells recorded in vitro was significantly different from that seen in vivo (F = 15.5, P < 0.001), which may reflect differences in the balance between deterministic and stochastic influences on spike occurrence. The study shows that while there is a rhythm of mean spike frequency, parameters based on the variability of interspike interval distributions also display rhythmic changes over the day-night cycle.

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Assessment of spike activity in the supraoptic nucleus.

Novel approaches to the characterization of coding carried by spike trains are discussed. Measuring firing frequency alone may only partially reflect spike patterning, and can only quantify changes of the most obvious kind. We have devised a method that combines probabilistic and information approaches to quantify the variability of the interspike intervals in a way that is independent of spike frequency. To illustrate the technique, the firing of an oxytocin cell and a vasopressin cell were compared before and after osmotic stimulation. A bimodal lognormal function was fitted to the interspike interval histograms. The entropy of the log interval histogram was used to measure the variability of intervals and to reflect the coding capacity of the cell per spike. A perfect metronome shows no variability in interval and thus has no greater coding capacity than is conveyed by its frequency, whereas the variability of intervals of magnocellular neurones means that their irregular activity has greater potential for coding. While the mean spike frequency increased in both the oxytocin and vasopressin cells in response to osmotic stimulation, the changes in their irregularity showed differences. Osmotic stimulation reduced the entropy of the oxytocin cell, reflecting an increase in the regularity of its spike activity. Conversely, osmotic stimulation had little effect on the entropy of the vasopressin cell. Such differences are not evident from a simple inspection of ratemeter activity. The comparison highlights the limitations of mean spike frequency as a measure of spike coding. Parameters based on the interspike intervals constitute informative measures of spike activity that allow objective comparisons to be made between the activity under different physiological conditions.

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Measuring spike coding in the rat supraoptic nucleus.

Measuring spike coding objectively is essential to establish whether activity recorded under one set of conditions is truly different from that recorded under another set of conditions. However, there is no generally accepted method for making such comparisons. Measuring firing frequency alone only partially reflects spike patterning. In this paper, novel quantities based on the logarithmic interspike intervals are proposed as useful measures of spontaneous activity. We illustrate the methods by comparing extracellular recordings from magnocellular cells of the rat supraoptic nucleus in vivo and in vitro and between oxytocin and vasopressin cells in vivo. A bimodal Gaussian function fitted to the log interspike interval histogram accurately described the distribution profile for very different types of activity. We introduce the entropy of the log interval distribution as a novel quantity that measures the capacity of a cell to encode information other than a constant instantaneous frequency. Unlike existing entropy measures that are based on spike counts, it quantifies the variability in the interval distribution. In addition, the mutual information between adjacent log intervals is proposed as an objective measure of patterned activity. For cells recorded in vivo and in vitro, there was no significant difference in mean spike frequencies but there were differences in the log interval entropy (t = -4.97, P < 0.001) and the mutual information (z = -2.64, P < 0.01). The differences may result from the disruption of connections in the slice preparation. When a comparison was made between the spike activity of oxytocin and vasopressin cells recorded in vivo, there was a difference in mutual information (z = 5.15, P < 0.001) but not in mean spike frequency. Both comparisons highlight the potential limitations of using mean spike frequency alone as a measure of spike coding. We propose that our novel parameters based on interval analysis constitute informative measures of spontaneous activity under different physiological conditions.

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