Pierluigi Lenzi

On the functional significance of the circuit of papez

Summary This study was performed with the aim of clarifying the functional properties of the circuit of Papez as a feedback loop regulating hippocampal activity. The circulation in the loop of volleys of impulses elicited by delivering to the hippocampus trains of low-frequency electrical stimuli was studied in the cat by recording unit activity at mammillary, thalamic, cingulate and hippocampal levels. The results show the properties of two feedback loops, one related to the nucleus anterior ventralis and the other to the nucleus anterior medialis. The output of the nucleus anterior ventralis is dependent on the hippocampal output, whereas the output of the nucleus anterior medialis is affected by both hippocampal and extralimbic thalamo-neocortical influences. The intermodulation of septal and feedback volleys at the level of the hippocampal region appears, in physiological conditions, to underlie the regulation of hippocampal bioelectrical activity in general and of theta rhythm in particular. A revelant effect of the output of the anterior thalamic nuclei consists in the depression of unit activity of the gyrus cinguli and area retrosplenialis.

Transfer of the hippocampal output by the anterior thalamic nuclei

Abstract This study was performed in the cat with the aim of clarifying the transfer properties of the thalamic nuclei anterior ventralis and anterior medialis with respect to volleys of impulses elicited by delivering trains of electrical stimuli of different frequency and intensity to the contralateral hippocampus. The results show that the responses of the nucleus anterior ventralis are only intensity-dependent whereas those of the nucleus anterior medialis depend on both stimulus intensity and frequency. The nucleus anterior ventralis performs an operation of input-output transfer within one of the loops of the Papez circuit. The nucleus anterior medialis is under the influence of both the hippocampus and a thalamoneocortical feedback activated by the output of the nucleus itself. This nucleus, therefore, operates as a gate controlling the integration of archicortical and neocortical activities.

Threshold of respiratory responses to preoptic heating during sleep in freely moving cats.

Abstract The respiratory effects of unilateral preoptic heating were studied during sleep in freely moving cats. Hypothalamic temperature was recorded by means of a thermistor placed about 5 mm posteriorly to the caudal electrode of the heating pair. Environmental temperature was kept at about 24–28 °C to maintain panting threshold low. Preoptic heating, increasing the hypothalamic temperature by 0.047 ± 0.001 °C, elicited thermal polypnoea or panting during slow-wave sleep, whereas during fast-wave sleep it raised hypothalamic temperature by 0.050 ± 0.003 °C above the value of treated slow-wave sleep but did not result in thermal polypnoea or panting. Only stronger heating, applied to the preoptic region until the hypothalamic temperature increase averaged 0.131 ± 0.009 °C above the value of treated slow-wave sleep, elecited thermal polypnoea during fast-wave sleep. The results show that the threshold of respiratory responses to preoptic heating is consistently increased during fast-wave sleep. The implications of this conclusion are discussed in terms of the homeostatic function of the hypothalamus.

Brain circulation during sleep and its relation to extracerebral hemodynamics

Regional cerebral blood flow (rCBF) was measured in rabbits during the sleep-waking cycle, using radioactive microspheres. rCBF does not change significantly in the transition from wakefulness (W) to synchronized sleep (SS), while it significantly increases during desynchronized sleep (DS). No correlation was found between CBF changes and changes in cardiac output or regional blood flows in the transition from SS to DS. This suggests that the CBF increase in DS is not relevantly affected by changes in extracerebral hemodynamic factors.

Sleep Modulates Hypertension in Leptin-Deficient Obese Mice

Leptin increases sympathetic activity, possibly contributing to hypertension in obese subjects. Hypertension increases cardiovascular mortality, with nighttime (sleep) blood pressure having a substantial prognostic value. We measured blood pressure in male leptin-deficient obese mice (ob/ob; n=7) and their lean wild-type littermates (+/+; n=11) during wakefulness, non–rapid-eye-movement sleep, and rapid-eye-movement sleep to investigate whether, in the absence of leptin, derangements of blood pressure are still associated with obesity and depend on the wake-sleep state. Mice were implanted with a telemetric pressure transducer and electrodes for discriminating wake-sleep states. Mean blood pressure was significantly higher in ob/ob than in +/+ mice during wakefulness (7.3±2.6 mm Hg) and non–rapid-eye-movement sleep (6.7±2.8 mm Hg) but not during rapid-eye-movement sleep (2.6±2.6 mm Hg). In ob/ob and +/+ mice, mean blood pressure was substantially higher during wakefulness than during non–rapid-eye-movement sleep. On passing from non–rapid-eye-movement sleep to rapid-eye-movement sleep, mean blood pressure decreased significantly in ob/ob but not in +/+ mice. The time spent during wakefulness was lower in ob/ob than in +/+ mice during the dark (active) period, whereas the opposite occurred during the light (rest) period. Consequently, mean blood pressure was significantly higher in ob/ob than in +/+ mice during the light (8.2±2.4 mm Hg) but not during the dark (3.0±2.9 mm Hg) period. These data suggest that, in the absence of leptin, obesity may entail hypertensive derangements of blood pressure, which are substantially modulated by the cardiovascular effects of the wake-sleep states.

Respiratory frequency as a function of preoptic temperature during sleep.

The effects on respiratory frequency of preoptic heating during slow-and fast-wave sleep were studied in freely moving cats. During slow-wave sleep, at neutral ambient temperature, the subliminal range of preoptic temperature for thermal polypnea extends to 0.2-0.4 degrees C above control preoptic temperature. During fast-wave sleep, at neutral ambient temperature, the subliminal range of preoptic temperature for thermal polypnea increases beyond 0.9-1.0 degrees C above control preoptic temperature. Moreover, the polypneic response is weak and unstable. The results show the suspension of a precise thermoregulatory control during fast-wave sleep in a homoiothermic species.

Mathematical modeling of cardiovascular coupling: Central autonomic commands and baroreflex control

The cross-correlation function (CCF) yields the correlation coefficient between spontaneous fluctuations of heart period and blood pressure as a function of the time shift between these variables. Two CCF patterns occur in humans: I) positive correlation between heart period and previous pressure values; II) negative correlation between heart period and subsequent pressure values. These patterns may result from the baroreflex and central autonomic commands (CAC), respectively. The aim of this study was to test this interpretation with a non-linear mathematical model of the human cardiovascular system. CAC were modeled as either phasic changes or random fluctuations of vagal and sympathetic activities with opposite sign. CCF pattern I resulted from baroreflex buffering of blood pressure changes elicited by vascular resistance fluctuations. When cardiac baroreflex control was absent or outweighed by CAC to the heart, simulations resulted in CCF pattern II only. In intermediate conditions when cardiac baroreflex interacted with CAC to the heart, CCF patterns I and II coexisted because the coupling between heart period and blood pressure varied with time. CAC to the heart decreased in magnitude the correlation coefficient and lengthened the time shift of CCF pattern I, thus apparently slowing and blunting baroreflex effects. Conversely, the baroreflex decreased in magnitude the correlation coefficient of CCF pattern II, thus blunting CAC effects. These results provide theoretical evidence in favor of application of the CCF analysis to investigate the balance between central autonomic and baroreflex cardiac control.

Sleep-Dependent Changes in the Coupling Between Heart Period and Arterial Pressure in Newborn Lambs

This study assessed whether sleep-dependent changes in the relationship between heart period (HP) and mean arterial pressure (MAP) occur in newborn life. Electrodes for electrocorticographic, electromyographic, and electrooculographic monitoring and an arterial catheter for blood pressure recordings were implanted in 11 newborn lambs. HP and MAP beat-to-beat values were computed from 120-s blood pressure recordings during quiet wakefulness, active sleep, and quiet sleep. For each recording, the time shift at which the maximum of the HP versus MAP cross-correlation function was attained was identified. For each lamb and wake-sleep state, an average correlation coefficient was then computed corresponding to the median value of such time shifts. The maximum of the cross-correlation function was attained with HP lagging behind MAP. The corresponding mean correlation coefficient was significantly higher in quiet sleep (0.51 ± 0.05) than either in quiet wakefulness (0.31 ± 0.05) or in active sleep (0.29 ± 0.03). Sleep-related differences in the correlation between HP and MAP were maintained after HP and MAP data were low-pass filtered at 0.3 Hz to remove their fast ventilatory oscillations. In conclusion, data indicate that the relationship between spontaneous fluctuations in HP and those in MAP is sleep-state dependent in newborn lambs. A positive HP versus MAP correlation with HP lagging behind MAP is consistent with baroreflex control of HP. Heart rhythm thus may be more tightly controlled by the baroreceptor reflex and less dependent on central autonomic commands in quiet sleep than either in quiet wakefulness or in active sleep.

Brain blood flow and extracerebral carotid circulation during sleep in rat.

Cerebral blood flow (CBF) and blood flow (BF) in extracerebral head structures were measured during the sleep-wake cycle in rats using radioactive microspheres. While no statistically significant changes occurred in the transition from Waking to quiet sleep (also referred to as synchronized or non-REM Sleep), CBF increased significantly in active sleep (AS, also referred to as desynchronized or REM Sleep) in all structures considered, with the sole exception of the cerebellum. In extracerebral head structures, no significant state-dependent BF changes were found. Factor Analysis however extracted a common factor accounting for BF variability in the external carotid circulation. This factor was uncorrelated with CBF changes in AS, suggesting independent regulation of the two vascular beds in this sleep state.

Hypothalamic temperature during desynchronized sleep

SummaryThe influence of changes in heat loss at specific heat exchangers, appraised by recording ear skin temperature (Ts), on the hypothalamic temperature (Thy) rise during desynchronized sleep (DS) was studied in unrestrained cats at different ambient temperatures (Ta). The correlations of initial and final Thy changes (ΔiThy and ΔfThy) with initial and final Ts changes (ΔiTs and ΔfTs), respectively, are statistically not significant. However, a significant negative correlation was found between ΔfiThy, i.e. ΔfThy-ΔiThy, and ΔfiTs, i.e. ΔfTs-ΔiTs. The latter result shows that only after its initial rise is Thy affected by changes in heat loss at specific heat exchangers during DS. Accordingly, ΔfThy and ΔfiThy are positively correlated with Ta. However, also ΔiThy, although not affected by heat loss changes at specific heat exchangers, shows a positive correlation with Ta. On the basis of these results and of the data in the literature, it is concluded that three independent factors underlie Thy changes during DS, namely heat loss at specific heat exchangers, hypothalamic blood flow and thermogenesis.