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Network oscillatory dynamics accompany cerebral bioenergetic defence in hypoxia.

A network physiology framework investigated how coordinated interactions among multiple organ systems collectively support the preservation of cerebral bioenergetic function and better distinguish adaptive from maladaptive responses to hypoxia. Twelve healthy males were passively exposed to 6 h of normoxia (21% O2) and hypoxia (12% O2) in a randomised, single-blind, crossover design. Venous blood was assayed for oxidative-nitrosative stress (OXNOS, spectroscopy/chemiluminescence) and neurovascular unit (hs-ELISA) biomarkers. Global cerebral delivery of O2 and glucose were determined by duplex ultrasound. Clinical acute mountain sickness (AMS+) was diagnosed in five participants. Cerebral substrate delivery was well maintained in both hypoxia and AMS+ (p < 0.05 vs normoxia and AMS-) despite marked arterial hypoxemia. Bioenergetic defence coincided with pronounced elevations in the spectral amplitude and phase synchronisation of very low-frequency oscillations (VLFOs, 0.03-0.06 Hz), which were evident across multiple organ systems and most prominent within the cerebral network. Systemic VLFOs were further exaggerated and more functionally connected in AMS+ in the absence of exaggerated systemic OXNOS or structural damage/destabilisation of the neurovascular unit (both p < 0.05 vs normoxia and AMS-). Collectively, these findings suggest that AMS, while characterised by debilitating symptomatology, may reflect a neuroprotective adaptive as opposed to pathologically maladaptive phenotype.

Humans

Oscillation of the human ankle joint in response to applied sinusoidal torque on the foot.

1. Low-frequency (3-30 Hz) oscillatory rotation of the ankle joint in plantarflexion-dorsiflexion was generated with a torque motor. Torque, rotation about the ankle and electromyograms (e.m.g.s) for the gastrocnemius-soleus and the anterior tibial muscles were recorded.2. Fourier coefficients at each drive frequency were used to calculate the effective compliance (ratio of rotation and torque). The compliance has a sharp resonance when tonic, voluntary muscle activity is present.3. The resonant frequency of compliance is between 3 and 8 Hz. The location of the resonant frequency and the magnitude of the compliance at resonance depend upon both the degree of tonic muscle activity and the amplitude of the driving torque. The resonant frequency increases with increasing tonic activity.4. With tonic muscle activity, the compliance in the frequency range below resonance increases with increasing amplitudes of driving torque.5. The e.m.g., when evoked by the rhythmic stretch, lags the start of stretching by between 50 and 70 msec.6. When tonic muscle activity is present, the resonant frequency of the stretch reflex is between 5 and 6.5 Hz.7. Following the start of driven oscillation at frequencies near resonance, slowly increasing amplitudes of angular rotation (to a limit) are observed.8. Distortion (from the sinusoidal wave shape) of angular rotation is frequently observed with drive frequencies between 8 and 12 Hz during which there sometimes occur spontaneous recurrences of oscillation at the drive frequency. For the angular rotation, a significant portion of the power may be in subharmonic frequency components of the drive frequency when that frequency is between 8 and 12 Hz.9. Self-sustaining oscillation (clonus) near the resonant frequency of the compliance is sometimes observed after the modulation signal to the motor is turned off. This is most often seen when the gastrocnemius-soleus muscles are fatigued. Clonus may be evoked by driven oscillation at any frequency.10. The hypothesis that physiological tremor, which occurs between 8 and 12 Hz, is a consequence of stretch reflex servo properties seems to be at odds with the observations of resonance in the compliance and of self-generated clonus both occurring in the 5-8 Hz region.

Adult

Neuronal correlates of siphon withdrawal in freely behaving Aplysia.

1. Central neuronal mechanisms of siphon withdrawal in Aplysia were studied for the first time in intact, freely behaving animals by means of population recordings from implanted whole-nerve cuff electrodes. Intracellular follow-up studies were then conducted when the same animal was reduced to a semi-intact preparation. 2. Background spontaneous activity in the siphon nerve consisted of low-frequency firing of a population of efferent units containing identified siphon motoneurons. 3. Spontaneous patterned bursts of efferent activity occurred irregularly and were associated with all-or-nothing contractions of the parapodia, gill, and siphon. Spontaneous bursts were due to centrally generated activity in the interneuron II (INT II) network, an oscillatory network with endogenous pacemaker properties. 4. In intact animals, even weak tactile stimuli to the siphon typically triggered an INTII burst shortly after the stimulus-locked efferent activity. Thus, the stimulus can phase-advance the INT II oscillator. In semi-intact preparations, short-latency INT II bursts were triggered less less frequently and required more intense stimuli. 5. With weak to moderate-intensity stimuli in intact animals, the presence of short-latency triggered INT II bursts largely determined the duration of the siphon component and amplitude of the gill component of the withdrawal reflex. 6. When stimuli were repeated over a range of interstimulus intervals (from 60 to 1 min), the likelihood of triggering a short-latency INT II burst die not change systematically. Thus, the ability of the siphon stimulus to stably entrain the all-or-none INT II component over a wide range of intervals will interact behaviorally with the decrement of the monosynaptic component of the reflex with repetition.

Animals