Biology subjects

Lesburgueres, E.

Publications and source records attributed to Lesburgueres, E..

3 recordsLinked to original sources

bioRxiv2024

Link between respiratory pauses and vigilance states in freely moving mice

Brain activity and breathing rate influence each other but it remains unclear how fine respiratory features vary across vigilance states. Using simultaneous nasal pressure and hippocampal local field potential recordings in freely-moving mice, we show that the position of respiratory pauses within breathing cycles distinguish Wake, Rapid Eye Movement (REM) and non-REM (NREM) sleep states. Model-based predictions of vigilance states based on respiratory features perform well even on animals outside of the training set, suggesting the rules are generalized. Respiratory features underwent specific changes at state transitions, such as progressive elimination of pauses after inhalation foreshadowing REM. During NREM, respiratory changes predicted moment-to moment sigma power variations beyond movement-defined packets delineated by micro-arousals, as pauses after inhalation fragmented NREM sleep into [~]30s windows of high sigma power. Overall, our findings reveal that respiratory features structure the macro- and micro-architecture of sleep, opening new windows into brain states through respiration.

neuroscience↗

bioRxiv2022

Phencyclidine disrupts neural coordination and cognitive control by dysregulating translation

BackgroundPhencyclidine (PCP) causes psychosis, is abused with increasing frequency, and was extensively used in antipsychotic drug discovery. PCP discoordinates hippocampal ensemble action potential discharge and impairs cognitive control in rats, but how this uncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist impairs cognition remains unknown. MethodsThe effects of PCP were investigated i) on hippocampal CA1 ensemble action potential discharge in vivo in urethane-anesthetized rats and during awake behavior in mice; ii) on synaptic responses in ex vivo mouse hippocampus slices; iii) in mice on a hippocampus-dependent active place avoidance task that requires cognitive control; and iv) on activating the molecular machinery of translation in acute hippocampus slices. Mechanistic causality was assessed by comparing the PCP effects to the effects of inhibitors of protein synthesis, group-1-type metabotropic glutamate receptors (mGluR1/5), and subunit-selective NMDARs. ResultsConsistent with ionotropic actions, PCP discoordinated CA1 ensemble action potential discharge. PCP caused hyperactivity, and impaired active place avoidance, despite learning the task before PCP. Consistent with metabotropic actions, PCP exaggerated protein-synthesis dependent DHPG-induced mGluR1/5-stimulated long-term synaptic depression (LTD). Pretreatment with anisomycin or the mGluR1/5-antagonist MPEP, both of which repress translation, prevented the PCP-induced discoordination, and the cognitive and sensorimotor impairments. PCP as well as the NR2A-containing NMDAR-antagonist NVP-AAM077 unbalanced translation that engages the AKT, mTOR and 4EBP1 translation machinery and increased protein synthesis, whereas the NR2B-containing antagonist Ro25-6981 did not. ConclusionsPCP dysregulates translation, acting through NR2A-containing NMDAR subtypes, recruiting mGluR1/5 signaling pathways, leading to the neural discoordination that is central to the cognitive and sensorimotor impairments.

neuroscience↗

bioRxiv2020

PKMζ traces hippocampal LTP maintenance and spatial long-term memory

PKM{zeta} is an autonomously active PKC isoform crucial for the maintenance of synaptic long-term potentiation (LTP) and long-term memory. Unlike other protein kinases that are transiently stimulated by second messengers, PKM{zeta} is persistently activated through sustained increases in kinase protein expression. Therefore, visualizing increases in PKM{zeta} expression during long-term memory storage might reveal the sites of its persistent action and thus the location of memory-associated LTP maintenance in the brain. Using quantitative immunohistochemistry validated by the lack of staining in PKM{zeta}-null mice, we examined the amount and distribution of PKM{zeta} in subregions of the hippocampal formation of wild-type mice during LTP maintenance and spatial long-term memory storage. During LTP maintenance in hippocampal slices, PKM{zeta} increases in the pyramidal cell body and stimulated dendritic layers of CA1 for at least 2 h. During spatial memory storage, PKM{zeta} increases in CA1 pyramidal cells for at least 1 month, paralleling the persistence of the memory. The subset of CA1 pyramidal cells that are tagged by immediate early gene Arc-driven transcription of fluorescent proteins, whose expression increases during initial memory formation, also expresses the persistent increase of PKM{zeta} during memory storage. In the memory-tagged cells, the increased PKM{zeta} expression persists in dendritic compartments within stratum radiatum for 1 month, indicating the long-term storage of information in the CA3-to-CA1 pathway during remote spatial memory. We conclude that persistent increases in PKM{zeta} trace the molecular mechanism of LTP maintenance and thus the sites of information storage within brain circuitry during long-term memory.

neuroscience↗