Dendritic Ih selectively blocks temporal summation of unsynchronized distal inputs in CA1 pyramidal neurons.

The active dendritic conductances shape the input-output properties of many principal neurons in different brain regions, and the various ways in which they regulate neuronal excitability need to be investigated to better understand their functional consequences. Using a realistic model of a hippocampal CA1 pyramidal neuron, we show a major role for the hyperpolarization-activated current, Ih, in regulating the spike probability of a neuron when independent synaptic inputs are activated with different degrees of synchronization and at different distances from the soma. The results allowed us to make the experimentally testable prediction that the Ih in these neurons is needed to reduce neuronal excitability selectively for distal unsynchronized, but not for synchronized, inputs.

Quantitative modeling of perception and production of time intervals.

The accurate perception/production of durations in the seconds and minutes range is important in a number of everyday activities, but the lack of direct experimental evidence on the neural circuits that could be involved has precluded the detailed elucidation of the underlying physiological mechanisms. We show, using a basic biophysical model of a timekeeping system and experimental data on time intervals produced or estimated under different conditions, that experimental values, variability, and distributions can be quantitatively explained in terms of a background synaptic activity such as that generated by attention. The model provides a plausible neural substrate for encoding time intervals, and the findings suggest how it may interplay at the single neuron level with the attentional system, to elaborate a subjective representation of the elapsing time.

A model of the effects of cognitive load on the subjective estimation and production of time intervals.

How and where the brain calculates elapsing time is not known, and one or more internal pacemakers or others timekeeping systems have been suggested. Experiments have shown that the accuracy in estimating or producing time intervals depends on many factors and, in particular, both on the length of the intervals to be estimated and on the additional, and unrelated, cognitive load required during the task. The psychological 'attentional approach' is able to explain the experimental data in terms of perturbations of a cognitive timer. However, the basic biophysical mechanisms that could be involved at the single neuron level are still not clear. Here we propose a computational model suggesting how the process to focus the attention on a non-temporal task could alter the perception of time intervals as observed in the experiments. The model suggests that an attention-based excitatory and/or inhibitory background synaptic noise, impinging on the pacemaker circuit, could represent both qualitative and quantitative features of the cognitive load. These effects are predicted to be independent of the number, location or specific implementations of the internal timing systems.

The influence of volume depletion and central hypovolemia on the plasma concentration of parathyroid hormone in dialysis patients.

Because changes in extracellular volume during dialysis cause reflex neurohonnonal changes that may influence parathyroid hormone (PTH) release independently of calcium, the influence of isotonic volume depletion (by isolated ultrafiltration) and central hypovolemia (70 degrees tilt) on serum PTH1-84 was studied in 16 hemodialysis patients. Tilting was performed in volume depleted state, i.e., immediately after hemodialysis. In the control study, patients underwent sham ultrafiltration (UF = 0) and after dialysis maintained the supine position for the same length of time they remained in the tilt position in the active experiment. Isolated ultrafiltration (-2.3 +/- SEM 0.3 L) caused a 21% fall in mean arterial pressure (from 101 +/- 6 to 80 +/- 6 mmHg, P < 0.01), a fall that was accompanied by a marked increase in plasma catecholamine levels (norepinephrine P < 0.001, epinephrine P < 0.025), in plasma renin activity (P < 0.001) and in plasma arginine vasopressin (P < O.001). Atrial natriuretic factor showed a slight reduction, whereas the plasma endothelin-1 level did not change. Serum Ca showed the expected, hemoconcentration-dependent rise (from 4.1 +/- 0.1 to 4.4 +/- 0.1 meq/L, P < 0.01). Interestingly, UF caused a marked rise in plasma PTH1-84 concentration (from 252 +/- 62 to 335 +/- 72 pg/ml, P < 0.01). UF-induced changes in serum PTH1-84 were related to norepinephrine changes (r = 0.57) as well as to plasma renin activity (r = 0.50). After hemodialysis, tilting induced a pronounced rise in serum PTH1-84 (from 102 +/- 29 to 200 +/- 55 pg/ml), and these changes were slightly related to plasma epinephrine (r = 0.49) but independent of other parameters. In the control experiment, neither sham UF nor recumbency modified serum PTH. In hemodialysis patients, serum PTH is sensitive to changes in extracellular and central blood volume of magnitude sufficient to decrease arterial pressure. Avoiding marked volume stimuli might help to refine the interpretation of the Ca/PTH curves during hemodialysis in these patients.

Influence of extracellular volume expansion on circulating PTH1-84 in subjects with mild essential hypertension.

The effect of acute volume expansion by saline (1 L/40 min) on serum parathyroid hormone (PTH) concentration was studied in 28 subjects with mild essential hypertension. At the zenith volume expansion there was a significant increase in systolic pressure (7 +/- 2 mm Hg, P < .01) while diastolic pressure and heart rate showed minor (NS) variations. The rise in systolic pressure was accompanied by a significant (P = .02) decrease in plasma ionized calcium (from 1.12 +/- 0.03 to 1.08 +/- 0.03 mmol/L) and by a marked PTH increase (from 36 +/- 3 to 60 +/- 4 pg/mL, P < .01). The arterial pressure variations were independent of changes in serum PTH. In a second experiment (n = 11), aimed at preventing the changes in calcium concentration brought about by hemodilution, we infused the same volume of saline with the addition of 1.25 mmol of elemental calcium. In this study PTH showed a small, nonsignificant, decrease while systolic pressure changes were similar to those of the first study (ie, an isolated 9 +/- 4 mm Hg increase in systolic pressure). In a third experiment (n = 7), aimed at studying the effect of raised plasma PTH concentration in isocalcemic conditions, PTH1-38 was continuously infused (1 ng/kg/min) during the volume expansion phase performed with the same solution as used in the second experiment. The hemodynamic changes were again identical to those of the other studies (an isolated 9 +/- 3 mm Hg increase in systolic pressure).(ABSTRACT TRUNCATED AT 250 WORDS)

Age related changes in total DNA and RNA and incorporation of uridine and thymidine in rat brain.

1. Total brain DNA and total brain RNA and the incorporation of thymidine[14C] and uridine[3H] were measured in young and aged rats. 2. From 20 days to the time of sexual maturation, both DNA and RNA levels increase. Total RNA exceeds total DNA at all ages. Comparatively, the ratio of total DNA/RNA is higher in young than in aged animals. 3. The incorporation of thymidine[14C]/g of DNA and of uridine[3H]/g of RNA decreases with age. This decrease is rapid in young animals. After 350 days of age, the incorporation becomes very low. The significance of data is discussed.

Age-related changes in total DNA and RNA and incorporation of uridine and thymidine in rat liver, kidney and spleen.

Total content of DNA and RNA in liver, kidney and spleen were measured in young and aged rats. At the same time the incorporation of [14C]thymidine, a DNA precursor, and [3H]uridine, an RNA precursor, were also determined. Changes in total organ DNA and RNA correlated with sexual maturation as did incorporation of precursors. Young animals have more DNA per organ relative to RNA, with kidney and spleen DNA showing a decrease between maturity and senescence. However, liver RNA increases with age, a change probably due to decreased catabolism of RNA since [3H]urine uptake decreases. Liver polyploid differentiation, and [14C]thymidine and [3H]uridine uptake, are correlated. In kidney, incorporation of [3H]uridine is inversely related to [14C]thymidine incorporation.

Temporal changes of [3H]uridine and [14C]thymidine incorporation and total organ DNA and RNA in rat thymus.

Aging at organ, cell and molecular levels is characterized by a variety of deleterious changes. Theoretically, all of these changes must be linked to the primary informational molecule DNA and its ancillary control proteins. The present experiments were done to determine how the rate of nucleotide uptake and/or total quantity of RNA and DNA vary with age. Thymus showed age-related changes in radionucleotide uptake and total quantity of RNA and DNA. The ratio of DNA to RNA is higher in organs of younger animals. Total organ thymus DNA decreased between maturity and senescence. Sexual maturation correlates with DNA and RNA in total organ content or in synthesis.

Temporal changes in histone acetylation.

The incorporation of tritiated acetate was studied in developing and aging rats. Thymus, liver and serum were collected 30 minutes after injection of acetate. The trichloroacetic acid precipitable histone fraction was then extracted from liver and thymus and its radioactivity determined. Serum and cytoplasmic fractions were also counted. Serum activity declined with age. Thymus histone and cytoplasmic fractions showed a cyclic pattern. Acetylation of liver histones showed a straight line decline to a relatively constant level. The decline in acetylation of liver histones is postulated to be due to repression of acetylation processes and is thought to parallel the change of hepatocytes from a diploid to a polyploid state.

Transition metals in calf thymus deoxyribonucleoprotein.

Fe, Ni, Cu and Zn were found by energy-dispersive X-ray fluorescence in calf thymus deoxyribonucleoprotein. The X-ray analyses indicated the absence of Cr, Mn and Co.