It is well established that Zif268/Egr1 , a member of the Egr family of transcription factors, is critical for the consolidation of several forms of memory; however, it is as yet uncertain whether increasing expression of Zif268 in neurons can facilitate memory formation. Here, we used an inducible transgenic mouse model to specifically induce Zif268 overexpression in forebrain neurons and examined the effect on recognition memory and hippocampal synaptic transmission and plasticity. We found that Zif268 overexpression during the establishment of memory for objects did not change the ability to form a long-term memory of objects, but enhanced the capacity to form a long-term memory of the spatial location of objects. This enhancement was paralleled by increased long-term potentiation in the dentate gyrus of the hippocampus and by increased activity-dependent expression of Zif268 and selected Zif268 target genes. These results provide novel evidence that transcriptional mechanisms engaging Zif268 contribute to determining the strength of newly encoded memories.

Although endoscopic studies in adult humans have suggested that laryngeal closure can limit alveolar ventilation during nasal intermittent positive pressure ventilation (nIPPV), there are no available data regarding glottal muscle activity during nIPPV. In addition, laryngeal behavior during nIPPV has not been investigated in neonates. The aim of the present study was to assess laryngeal muscle response to nIPPV in nonsedated newborn lambs. Nine newborn lambs were instrumented for recording states of alertness, electrical activity [electromyograph (EMG)] of glottal constrictor (thyroarytenoid, TA) and dilator (cricothyroid, CT) muscles, EMG of the diaphragm (Dia), and mask and tracheal pressures. nIPPV in pressure support (PS) and volume control (VC) modes was delivered to the lambs via a nasal mask. Results show that increasing nIPPV during wakefulness and quiet sleep led to a progressive disappearance of Dia and CT EMG and to the appearance and subsequent increase in TA EMG during inspiration, together with an increase in trans-upper airway pressure (TUAP). On rare occasions, transmission of nIPPV through the glottis was prevented by complete, active glottal closure, a phenomenon more frequent during active sleep epochs, when irregular bursts of TA EMG were observed. In conclusion, results of the present study suggest that active glottal closure develops with nIPPV in nonsedated lambs, especially in the VC mode. Our observations further suggest that such closure can limit lung ventilation when raising nIPPV in neonates. thyroarytenoid muscle; cricothyroid muscle; diaphragm; states of alertness; intermittent positive-pressure ventilation NASAL INTERMITTENT positive-pressure ventilation (nIPPV) is increasingly used in the neonatal period (12) as treatment for respiratory distress syndrome (22) and apneas of prematurity (3,27) and as a bridge between endotracheal tube ventilation and spontaneous ventilation (6,19). Previous studies using endoscopic observations in adult humans have shown that laryngeal closure can occur during nIPPV, especially in the volume control (VC) mode (17, 18, 34 -36). In addition, laryngeal closure appears to increase with increasing ventilatory support, together with decreasing subglottal (alveolar) ventilation (40). Such laryngeal behavior is of high clinical importance since it has been linked to falls in oxygen saturation when increasing nIPPV during sleep in adult humans (7) and could divert positive pressure from the airways, leading to increased gastric distension (11). However, although the glottal closure observed endoscopically during nIPPV suggests an active contraction of glottal constrictor muscles, there are, to our knowledge, no data on glottal muscle electromyograms (EMG) during nIPPV. Moreover, there are no currently available studies on laryngeal dynamics during nIPPV in the neonatal period. Thus the aim of the present study was to test the hypotheses that 1) glottal narrowing during nIPPV is also present in the neonatal period, especially in the VC mode; and 2) glottal...

-Bussière, Pierre-Hugues Fortier, and Jean-Paul Praud. Laryngeal chemoreflexes induced by acid, water, and saline in nonsedated newborn lambs during quiet sleep.

The present study was aimed at investigating the effects of nasal continuous positive airway pressure (nCPAP; 6 cmH2O) or intermittent positive pressure ventilation (nIPPV; 10/4 cmH2O) on nonnutritive swallowing (NNS) and on the coordination between NNS and phases of the respiratory cycle, while taking into account the potential effects of states of alertness. Twelve full-term lambs were chronically instrumented at 48 h after birth for polysomnographic recordings, including NNS, diaphragm electromyographic activity, respiratory movements, pulse oximetry, and states of alertness. Studies in control conditions, with nCPAP and nIPPV, were performed in random order in nonsedated lambs at 4, 5, and 6 days of life. Results demonstrate that nCPAP significantly decreased overall NNS frequency, more specifically isolated NNS during quiet sleep and bursts of NNS in active sleep. In comparison, the effects of nIPPV on NNS frequency were more variable, with an inhibition of NNS only in wakefulness and an increase in isolated NNS frequency in active sleep. In addition, neither nCPAP nor nIPPV disrupted the coordination between NNS and phases of the respiratory cycle. In conclusion, nCPAP inhibits NNS occurrence in newborn lambs. Clinical relevance of this novel finding is related to the importance of NNS for clearing the upper airways from secretions and gastric content frequently regurgitated in the neonatal period.