Flies lacking all synapsins are unexpectedly healthy but are impaired in complex behaviour

Vertebrate synapsins are abundant synaptic vesicle phosphoproteins that have been proposed to fine-regulate neurotransmitter release by phosphorylation-dependent control of synaptic vesicle motility. However, the consequences of a total lack of all synapsin isoforms due to a knock-out of all three mouse synapsin genes have not yet been investigated. In Drosophila a single synapsin gene encodes several isoforms and is expressed in most synaptic terminals. Thus the targeted deletion of the synapsin gene of Drosophila eliminates the possibility of functional knock-out complementation by other isoforms. Unexpectedly, synapsin null mutant flies show no obvious defects in brain morphology, and no striking qualitative changes in behaviour are observed. Ultrastructural analysis of an identified 'model' synapse of the larval nerve muscle preparation revealed no difference between wild-type and mutant, and spontaneous or evoked excitatory junction potentials at this synapse were normal up to a stimulus frequency of 5 Hz. However, when several behavioural responses were analysed quantitatively, specific differences between mutant and wild-type flies are noted. Adult locomotor activity, optomotor responses at high pattern velocities, wing beat frequency, and visual pattern preference are modified. Synapsin mutant flies show faster habituation of an olfactory jump response, enhanced ethanol tolerance, and significant defects in learning and memory as measured using three different paradigms. Larval behavioural defects are described in a separate paper. We conclude that Drosophila synapsins play a significant role in nervous system function, which is subtle at the cellular level but manifests itself in complex behaviour.     

Relationship between daily physical activity and ANS activity in patients with CHF

PURPOSE: Heart rate variability (HRV) indices are powerful independent prognostic factors of cardiovascular events and all cause mortality in patients with chronic heart failure (CHF). This study evaluates the influence of lifestyle on HRV in CHF patients. METHODS: Thirty-nine CHF patients (33 men, ischemic/dilated cardiomyopathy (18/21), 52.4 +/- 11.2 yr, NYHA I to III, LVEF 33.4 +/- 5.1%) filled out a physical activity questionnaire providing an individual complete qualitative and quantitative picture of their physical activity and daily energy expenditure (PAEE/DEE) corrected for age, weight, severity of the condition and autonomy. Frequency and time domain indices of HRV were calculated from ECG Holter recordings on a typical weekday. Nighttime indices were calculated in order to avoid the confounding factor of physical activity that might alter 24-h frequency analysis of HRV. RESULTS: DEE was significantly different between classes I and II and classes I and III (P = 0.01 both) patients. Time spent in activities above 3 METs decreased significantly with the severity of the condition. Global and parasympathetic indices of 24-h HRV analysis were correlated to DEE and PAEE (Ptot24h = 78.80*PAEE (J x min x kg) -1061.80, R = 0.72, P < 0.0001). Multiple regression analysis revealed that PAEE was the sole independent factor on established HRV prognostic indices (P < 0.05) and especially within PAEE dimensions, only activities above 3 METs were correlated with established prognostic HRV indices (P < 0.05). CONCLUSION: These results indicate that rather than total DEE, moderate to intensive physical activity may counteract the decline in HRV with chronic heart disease. This may be linked to longer time spent in higher intensity activities, and not to total activity time.     

Cardiac interbeat interval increment for the identification of obstructive sleep apnea

The prevalence of obstructive sleep apnea syndrome (OSAS) is high in developed countries but its diagnosis is costly. Based on physiological evidence, the frequency component of heart rate variability (HRV) was evaluated as a simple and inexpensive diagnostic tool in OSAS. The predictive accuracy of frequency-domain HRV variables obtained from 24-hour ECG Holter monitoring (the power spectral density of the interbeat interval increment of very low frequencies, "VLFIpsd," and its percentage over the total power spectral density, "% VLFI"), and of established time-domain HRV variables were analyzed by comparison with respiratory disturbances indexes assessed by complete polysomnography in 124 consecutive patients (98 men aged 53.8 +/- 11.2 years) with clinically suspected OSAS. OSAS was present in 54 (43.5%) patients according to standard criteria. Using receiver operating characteristic curve analysis, two of the three most powerful predictors were frequency-domain variables: % VLFI (W = 0.80, P < 0.0001), and VL-FIpsd (W = 0.79, P < 0.0001). Using a multiple logistic regression analysis, %VLFI was the most strongly associated with diseased status (adjusted OR: 8.4; 95% CI: 3.4-19.5). Using an appropriate threshold, %VLFI demonstrated a diagnostic sensitivity of 87%. A 3-month continuous positive airway pressure treatment significantly improved the same parameter. Frequency-domain analysis of the interbeat interval increment appears as a powerful tool for OSAS diagnosis and follow-up. The simplicity of its analysis and of its use makes of it a well-suited variable for mass screening of OSAS patients.     

Frequent and prolonged asymptomatic episodes of paroxysmal atrial fibrillation revealed by automatic long-term event recorders in patients with a negative 24-hour Holter

The presence, frequency, and duration of episodes of paroxysmal atrial fibrillation (PAF) is difficult to establish. This is caused by the limited duration of standard Holter recordings and to the unsatisfactory yield of patient-triggered event recorders, because of asymptomatic events and of an inconsistent use of the patient dependent triggering function. A prospective cohort of 65 consecutive patients with recurrent palpitations and a negative 24-hour ECG Holter was investigated by means of a cardiac event recorder bearing continuous automatic arrhythmia analysis and storage. Over a mean duration of 77 +/- 36 hours, episodes of PAF were diagnosed in 20 (31%) patients, who had a total of 37 episodes; mean duration of PAF episodes was 7 hours 50 minutes +/- 8/hours 45 minutes (minimum 45 minutes, maximum 28 hours). Eleven (55%) of these 20 patients were asymptomatic and would have remained undiagnosed without the automatic mode of the event recorder. Asymptomatic PAF episodes were longer than symptomatic ones (10 hours 30 minutes +/- 6 hours 30 minutes vs 4 hours 50 minutes +/- 4 hours, P < 0.05). In addition, episodes of sustained paroxysmal supraventricular tachycardia (PSVT) were diagnosed in 39 (57%) patients, of whom 34 (87%) were symptomatic. In this prospective cohort, a second standard 24-hour monitoring would have missed 44% of the patients with PAF or PSVT and a classical patient-triggered event recorder 13%. In patients still complaining of palpitations after one negative 24-hour Holter, numerous, prolonged, and often asymptomatic episodes of PAF can be revealed by long-term automatic event recorders. These devices should help clarify the clinical consequences of such episodes.     

Autonomic adaptations to intensive and overload training periods: a laboratory study

PURPOSE: Looking for practical and reliable markers of fatigue is of particular interest in elite sports. One possible marker might be the autonomic nervous system activity, known to be well affected by physical exercise and that can be easily assessed by heart rate variability. METHODS: We designed a laboratory study to follow six sedentary subjects (32.7 +/- 5.0 yr) going successively through 2 months of intensive physical training and 1 month of overload training on cycloergometer followed by 2 wk of recovery. Maximal power output over 5 min (Plim5'), VO(2) and standard indices of heart rate variability were monitored all along the protocol. RESULTS: During the intensive training period, physical performance increased significantly VO(2peak) : +20.2%, < 0.01; Plim5': +26.4%, < 0.0001) as well as most of the indices of heart rate variability (mean RR, Ptot, HF, rMSSD, pNN50, SDNNIDX, SDNN, all < 0.05) with a significant shift in the autonomic nervous system toward a predominance of its parasympathetic arm (LF/HF, LFnu, HFnu, < 0.01). During the overload training period, there was a stagnation of the parasympathetic indices associated to a progressive increase in sympathetic activity (LF/HF, < 0.05). During the week of recovery, there was a sudden significant rebound of the parasympathetic activity (mean RR, HF, pNN50, rMSSD, all < 0.05). After 7 wk of recovery, all heart rate variability indices tended to return to the prestudy values. CONCLUSION: Autonomic nervous system status depends on cumulated physical fatigue due to increased training loads. Therefore, heart rate variability analysis appears to be an appropriate tool to monitor the effects of physical training loads on performance and fitness, and could eventually be used to prevent overtraining states.     

Effects of training in normoxia and normobaric hypoxia on time to exhaustion at the maximum rate of oxygen uptake

The effects of endurance training in normoxia or in hypoxia on time to exhaustion (T_lim) at the work rate corresponding to peak oxygen uptake (O_2peak) were examined at sea level in 13 healthy subjects. Before and after training the subjects performed the following: (1) incremental exercises up to exhaustion to determine peak oxygen uptake in normoxia (O_2peakN), the percentage of this value at the 4 mmol l^–1 blood lactate concentration (O₂4%N) and the work rate corresponding to O_2peakN (Pa_peakN), (2) a 5-min 90% Pa_peakN exercise followed by a 10-min passive recovery to determine the maximal blood lactate concentration (La_max) measured during the recovery, and (3) a T_lim at Pa_peakN. Training consisted of pedalling 2 h a day, 6 days a week, for 4 weeks. Five subjects trained in normobaric hypoxia [HT; partial pressure of inhaled oxygen (P_IO₂) 89 mmHg] and eight subjects trained at the same relative work rates in normoxia (NT; P_IO₂ 141 mmHg). The training-induced improvement of all the measured parameters were closely matched between the HT and the NT (P>0.05). Training increased T_lim by 59.7% [164(40) s]. The value of T_lim was related to O₂4%N and to La_max before and after training. Also, the training-induced improvement of T_lim was related to the concomitant decrease in La_max. It is concluded that: (1) endurance training including continuous high-intensity exercises improves T_lim for exercises performed at the same relative (higher absolute) work rate after training, (2) intermittent hypoxic training has no potentiating effect on T_lim as compared with training in normoxia, and (3) the intra-individual training-induced improvement of T_lim was associated with metabolic alteration in relation to lactate accumulation.     

Reference frames for representing visual and tactile locations in parietal cortex

The ventral intraparietal area (VIP) receives converging inputs from visual, somatosensory, auditory and vestibular systems that use diverse reference frames to encode sensory information. A key issue is how VIP combines those inputs together. We mapped the visual and tactile receptive fields of multimodal VIP neurons in macaque monkeys trained to gaze at three different stationary targets. Tactile receptive fields were found to be encoded into a single somatotopic, or head-centered, reference frame, whereas visual receptive fields were widely distributed between eye- to head-centered coordinates. These findings are inconsistent with a remapping of all sensory modalities in a common frame of reference. Instead, they support an alternative model of multisensory integration based on multidirectional sensory predictions (such as predicting the location of a visual stimulus given where it is felt on the skin and vice versa). This approach can also explain related findings in other multimodal areas.     

Leg extensor power and dehydroepiandrosterone sulfate, insulin-like growth factor-I and testosterone in healthy active elderly people

We examined the association between quadriceps muscle function and serum levels of dehydroepiandrosterone sulphate (DHEAS), insulin-like growth factor I (IGF-I) and testosterone in a group of healthy elderly people. Fifty-three independent, community-dwelling elderly subjects (26 men and 27 women) aged from 66 to 84 years volunteered to participate in the study. Physical activity (PA) was evaluated by a questionnaire. Quadriceps maximal muscle power (W˙ _max) and optimal shortening velocity (v _opt) were measured on a friction-loaded non-isokinetic cycle ergometer. The W˙ _max is expressed in relation to body mass (W˙ _max/kg, W · kg⁻¹), and in relation to the mass of the two quadriceps muscles (W˙ _max/Quadr, W · kg_Quadr ⁻¹). In women, when adjusted for age, anthropometric measurements and PA indices, IGF-I correlated significantly with W˙ _max/kg (partial correlation: r=0.59; P=0.001), W˙ _max/Quadr (r=0.58; P=0.002) and v _opt (r=0.53; P=0.004), whereas DHEAS was correlated significantly with W˙ _max/kg (r=0.54; P=0.003) and W˙ _max/Quadr (r=0.58; P=0.002). No such correlation was found in men. These findings indicate that in healthy elderly women lower values for quadriceps muscle W˙ _max and v _opt are related, independently of age, anthropometric measurements and PA indices, to lower circulating levels of DHEAS and IGF-I. Accepted: 29 December 1999     

Anatomical optimization of skin electrode placement to record electromyographic activity of <Emphasis Type="Italic">erector spinae</Emphasis> muscles

Fine analysis of body movements is now technologically feasible, together with simultaneous recording of multiple muscle activity. This is especially true for the trunk and back muscles during human walking. However, there have been few anatomic studies of the area where deep back muscle activity is recordable by skin electrodes. We therefore attempted to optimize skin electrode location for recording erector spinae muscle activity at different levels of the back. For this purpose, 20 dissections of the posterior wall of the trunk were performed. The cutaneous plane was reclined on both sides to expose the superficial muscles of the posterior wall of the trunk. We dissected then plane-by-plane until we exposed the erector spinae muscles. The widths of the fascial spinal muscle insertions were measured at spinal levels easily identified clinically, i.e., C7, T3, T7, T12 and L4. Electromyographic assessment of the electrode location at these levels was performed in three subjects. Erector spinae muscle activity proved possible to record on several areas of the posterior wall through a superficial muscle aponeurosis. We propose a protocol for placing skin electrodes to record erector spinae muscle activity based on clinical anatomical references.