Ringraziamo tutti i membri del laboratorio per il loro contributo alla scrittura e attenta lettura di questo manoscritto. Siamo grati a Paul Franken per stimolare le discussioni, il Dr. Gisèle Ferrand per i commenti utili sul protocollo chirurgico e il dottor Jean-Yves Chatton per fornire i file eseguibili Labview originale per l&#39;esposizione al rumore. Il finanziamento è stato fornito dalla Fondazione nazionale della scienza nazionale (Grants 31003A_146244 e 31003A_166318) e l&#39;Etat de Vaud.

<ol>
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B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Novel+object+presentation+affects+sleep-wake+behavior+in+rats.">Novel object presentation affects sleep-wake behavior in rats.</a> Neurosci Lett. 328 (1), 41-44 (2002).</li><li>Wimmer, R. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sustaining+sleep+spindles+through+enhanced+SK2-channel+activity+consolidates+sleep+and+elevates+arousal+threshold.">Sustaining sleep spindles through enhanced SK2-channel activity consolidates sleep and elevates arousal threshold.</a> J Neurosci. 32 (40), 13917-13928 (2012).</li><li>Fernandez, L. M. 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Gli autori dichiarano di non avere interessi finanziari concorrenti.

Qui mostriamo come stabilire un profilo temporale continuo di sonno non REM che integra le variabili EEG, EMG e ECG. Questo è un primo passo verso lo sviluppo di una descrizione integrativa del sonno del mouse, che può aiutare a identificare la scadenza temporale non riconosciuta in precedenza in cui sono organizzate elevate e basse resistenze al rumore durante il sonno non REM 1 . Una struttura temporale simile è stata descritta anche nel sonno non-REM umano attraverso un&#39;analisi analoga ...

Il sonno dei mammiferi è uno stato comportamentale di riposo e di resistenza agli stimoli ambientali. Nonostante questa apparente uniformità, i parametri polisomnografici e autonomi indicano che il sonno si muove tra stati nervosi e somatici qualitativamente e quantitativamente diversi su varie scale temporali e spaziali 1 . Durante i minuti a decine di minuti, si verifica il passaggio tra il sonno non REM e REM. Il sonno non REM è accompagnato da un&#39;ampia ampiezza e bassa frequenza nell&#39;EEG, con un picco spettrale intorno a ~ 0,5-4 Hz, mentre il sonno REM mostra un&#39;attività regolare di EEG nella banda theta (6-10 Hz), insieme a Muscolo atonia 2 . All&#39;interno del sonno non REM, gli esseri umani attraversano la luce (S2) e il sonno profondo dell&#39;onda lenta (SWS). Come indica la loro denominazione, queste due fasi mostrano rispettivamente soglie di aroazione inferiori e superiori 3 , 4 e differiscono in primo luogo dalla densità di bassa frequenzaEnte corticale EEG, indicata come attività a onde lente (SWA, 0,75-4 Hz). La non uniformità persiste durante i singoli attacchi di S2 e SWS dal minuto al sotto secondario, come documentato ampiamente dalla presenza variabile di SWA nel corso di un incontro 5 , 6 , ma anche da EEG e dai ritmi potenziali in campo Frequenze superiori, comprese le onde del mandrino nella banda sigma (10-15 Hz) e ritmi gamma (80-120 Hz) (per una recensione, vedi 7 , 8 , 9 , 10 ). Piuttosto che essere sottili, queste variazioni spostano lo stato corticale del sonno negli esseri umani agli estremi dello spettro. Per il sonno non REM, questi variano da una predominanza di SWA a stati che approssimano l&#39;attività sveglia perché contengono una parte sostanziale di componenti ad alta frequenza 11 <suP&gt;, 12 . Nei roditori e nei gatti, anche se il sonno non-REM non è suddiviso in fasi, emerge un breve periodo chiamato sonno intermedio (IS) prima dell&#39;insorgenza del sonno REM 13 . Durante IS, le funzioni di sonno REM, come l&#39;attività ippocampale theta e le onde ponto-geniculo-occipitali, iniziano, mentre le firme del sonno non-REM, come le onde mandrino e SWA, sono ancora presenti, indicando un mix tra i due stati di sonno 14 , 15 . Tuttavia, l&#39;IS potrebbe essere funzionalmente distinto poiché è modulata dagli antidepressivi 16 e attraverso una nuova presentazione di oggetti durante la veglia precedente 17 e contribuisce a impostare la soglia di eccitazione 18 . Inoltre, i diagrammi dello spazio statale dei parametri EEG e EMG di ratti liberamente in movimento mostrano un gruppo di punti 14 che è continuo tra il sonno non REM, il sonno REM e la veglia. Ci sono anche discontinuità sporadiche in SWA, senza entrare nella sveglia o nel sonno REM, che porta a notevoli fluttuazioni nella presenza relativa dei componenti a bassa e alta frequenza durante un incontro non letto REM non consolidato 14 , 19 e 20 . Infine, i rapporti variabili di SWA e ritmi di frequenza più alti durante il sonno non REM si verificano non solo nel tempo, ma mostrano anche differenze regionali in ampiezza e sincronizzazione tra aree corticali 19 . Il sonno non-REM del mammifero è ben lungi dall&#39;essere uniforme. Tuttavia, se tale non uniformità porta a stati che differiscono per funzioni e attributi comportamentali, non è chiaro. In diversi tipi di disturbi del sonno, il sonno continuo viene interrotto da risvegli spontanei e comportamenti motori inappropriati. Inoltre, le analisi spettrali mostrano alterazioni nella presenza relativa di frequenze più alte nell&#39;EEG 21E in parametri autonomi, come i tassi di respirazione e battito cardiaco 22 . La sequenza ordinata di stati di sonno stabili è perciò turbata e gli elementi di eccitazione corticale e / o autonomica intrudono in maniera incontrollata. Pertanto, la comprensione del continuum degli stati di sonno è di una possibile rilevanza per la malattia. Inoltre, la perturbazione del sonno da rumore ambientale negli ambienti urbani è associata a rischi sanitari generali, rendendo cruciale identificare momenti di maggiore vulnerabilità durante il sonno 23 . Gli esperimenti di arousal comportamentali nel sonno degli esseri umani indicano che è più difficile svegliarsi dal sonno non-REM dominato da SWA (fase S3), mentre il sonno non-REM leggero (fase S2) e il sonno REM mostrano soglie comparabili e inferiori di stimolazione 4 . L&#39;elaborazione corticale di stimoli sonori corti varia sensibilmente tra il sonno REM, S2 e S3 24 ,25 , indicando che i modelli di attività corticali specifici dello stato modulano le prime fasi dell&#39;elaborazione sensoriale. Per il sonno non REM nell&#39;uomo, la propensione a svegliarsi in risposta al rumore varia con la presenza di onde mandrino e ritmi alfa nell&#39;EEG 26 , 27 , 28 . La ritmicità talamocorticale durante i mandrini è accompagnata da una maggiore inibizione sinaptica sia ai livelli talamici che a quelli corticali, che si suppone contribuiscano all&#39;attenuazione dell&#39;elaborazione sensoriale 7 . Come sono i periodi di sonno resistenti ai rumori e vulnerabili organizzati nel tempo e quali sono i loro determinanti? In entrambi i topi e umani, abbiamo recentemente individuato una oscillazione infrarossa, 0,02-Hz nei ritmi neurali. A seconda della fase di questa oscillazione di 0,02-Hz, i topi hanno mostrato una reattività variabile agli stimoli esterni, sia svegliarsi o dormireIl rumore. È interessante notare, questa oscillazione è stata correlata con il tasso del battito cardiaco, indicando che il sistema nervoso autonomo partecipa nella modulazione della vulnerabilità del sonno agli stimoli esterni 1. Durante questo ritmo sono stati organizzati anche ritmi ippocampali correlati alla memoria e, in modo più sorprendente, la sua forza è correlata alla qualità del consolidamento della memoria negli esseri umani. L&#39;oscillazione di 0,02 Hz sembra quindi essere un principio organizzativo di sonno non umano REM e rodente che modula sia la sensibilità all&#39;ambiente che l&#39;elaborazione della memoria interna. Ciò sottolinea nuovamente la necessità di valutazioni multiparametriche e continue di stati di sonno per riconoscere la loro funzionalità e per individuare siti di potenziale vulnerabilità. Ecco una procedura per estrarre la forma d&#39;onda di queste dinamiche, incluso l&#39;impianto chirurgico dei topi per le misure combinate EEG / ECoG e EMG-ECG, l&#39;esposizione a stimoli sensoriali,Rutine di analisi. Questa procedura fornisce una base per la visualizzazione del sonno come uno stato di vigilanza continuamente variabile ma altamente organizzato durante il quale vengono eseguite diverse funzioni fondamentali del sonno in sequenza. Più in generale, la procedura è applicabile agli approcci che mirano ad estrarre le caratteristiche spettrali e autonome che precedono un esito comportamentale durante il sonno sia negli stati di salute che nelle malattie.

<table><tbody><tr><td>2-components epoxy glue</td><td>Henkel</td><td>Loctite EA 3450</td><td></td></tr><tr><td>Absorbable Suturing Fiber (Prolene)</td><td>Ethicon</td><td>5-0 FS-3</td><td></td></tr><tr><td>Adson Forceps</td><td>FST</td><td>11006-12</td><td></td></tr><tr><td>Antiseptic swab</td><td>VWR</td><td>149-0332</td><td></td></tr><tr><td>Attane Isoflurane</td><td>Piramal</td><td>Isoflurane 250mL</td><td></td></tr><tr><td>Connectors 3 x 2-channels</td><td>ENA AG</td><td>2.316</td><td>Raster 2.54 x 2.54 mm; size 5 x 8 x 9 mm; pin size 5 mm; http://www.ena.ch/</td></tr><tr><td>Dragonfly commutator</td><td>Dragonfly</td><td>Model #SL-10</td><td></td></tr><tr><td>EMBLA amplifier</td><td>EMBLA</td><td>A10 amplifier</td><td></td></tr><tr><td>Fine scissors</td><td>FST</td><td>14108-09</td><td></td></tr><tr><td>Flat Head Gold-plated steel screw</td><td>J.I. Morris</td><td>FF00CE125</td><td>https://jimorrisco.com/</td></tr><tr><td>Gold wire</td><td>CMSA</td><td>T.69 5gr</td><td>http://www.cmsa.ch/en/</td></tr><tr><td>Hemostatic sponge</td><td>Pfizer</td><td>Gelfoam</td><td></td></tr><tr><td>iodine-based disinfectant (Betadine)</td><td>Mundipharma</td><td>standart solution 60mL</td><td></td></tr><tr><td>Komet drill steel 1/005PM104</td><td>UNOR AG</td><td>22310</td><td></td></tr><tr><td>Matlab Analysis Software</td><td>MathWorks</td><td>R2016b</td><td>https://ch.mathworks.com/products/matlab.html</td></tr><tr><td>Microdrill</td><td>Fine Science Tools</td><td>96758</td><td></td></tr><tr><td>Mouse Gas Anesthesia Head Holder</td><td>Kopf Instruments</td><td>Model 923-B</td><td>http://kopfinstruments.com/product/model-923-b-mouse-gas-anesthesia-head-holder/</td></tr><tr><td>Ophtalmic ointment</td><td>Pharmamedica</td><td>VITA-POS</td><td></td></tr><tr><td>Paladur (liquid)</td><td>UNOR AG</td><td>2260215</td><td>for dental cement</td></tr><tr><td>Palavit (powder)</td><td>UNOR AG</td><td>5410929</td><td>for dental cement</td></tr><tr><td>Small Animal Stereotaxic Frame</td><td>Kopf Instruments</td><td>Model 930</td><td>http://kopfinstruments.com/product/model-930-small-animal-stereotaxic-frame-assembly/</td></tr><tr><td>Soldering wire</td><td>Stannol</td><td>593072</td><td></td></tr><tr><td>Temperature controller - Mini rectal probe</td><td>Phymep</td><td>4090502</td><td>http://www.phymep.com/produit/dc-temperature-controller/</td></tr><tr><td>Temperature controller- heating pad</td><td>Phymep</td><td>4090205</td><td>http://www.phymep.com/produit/dc-temperature-controller/</td></tr></tbody></table>

quantifying infra-slow dynamics of spectral power and heart rate in sleeping mice

Tre stati di vigilanza dominano la vita dei mammiferi: la veglia, il sonno non rapido (non REM) e il sonno REM. Poiché sono stati identificati più correlati neurali del comportamento negli animali in libertà di movimento, questa suddivisione a tre livelli diventa troppo simile. Durante la veglia, gli esempi delle attività corticali globali e locali, insieme ai parametri periferici come il diametro pupillare e l&#39;equilibrio simpatico, definiscono diversi gradi di eccitazione. Rimane ancora chiaro la misura in cui il sonno forma anche un continuum di stati cerebrali, all&#39;interno del quale il grado di resilienza agli stimoli sensoriali e l&#39;arousabilità, e forse altre funzioni del sonno, variano gradualmente, e come gli stati fisiologici periferici co-variano. La ricerca che avanza i metodi per monitorare più parametri durante il sonno, nonché attribuire alle costellazioni di questi attributi funzionali, è fondamentale per raffinare la nostra comprensione del sonno come un processo multifunzionale durante il quale molti effetti benefici devono essere exeseguita sempre. L&#39;individuazione di nuovi parametri che caratterizzano gli stati di sonno aprirà opportunità per nuovi percorsi diagnostici nei disturbi del sonno. Presentiamo una procedura per descrivere le variazioni dinamiche degli stati di sonno non-REM del mouse attraverso il monitoraggio e l&#39;analisi combinati di elettroencefalogrammi (EEG) / electrocorticogram (ECoG), elettromiogramma (EMG) e segnali elettrocardiogrammi (ECG) usando tecniche standard di registrazione polisomnografiche. Utilizzando questo approccio, abbiamo scoperto che il mouse non-REM sonno è organizzato in cicli di oscillazioni neurali e cardiache coordinate che generano intervalli di 25 secondi di alta e bassa fragilità agli stimoli esterni. Pertanto, i sistemi nervosi centrali e autonomi sono coordinati per formare stati di sonno comportamentali distinti durante il sonno non consolidato REM. Presentiamo manipolazioni chirurgiche per il monitoraggio polisomnografico ( cioè EEG / EMG combinato con ECG) per monitorare questi cicli nel mouse liberamente addormentato, l&#39;analisi a quantiFy la loro dinamica e i protocolli di stimolazione acustica per valutare il loro ruolo nella probabilità di svegliarsi. Il nostro approccio è stato già esteso al sonno umano e promette di svelare i principi comuni di organizzazione di stati di sonno non-REM nei mammiferi.

La figura 2 A (pannello superiore) mostra 100 min di tratti spontanei di sonno-sveglia, registrati mediante elettrodi polisomnografi impiantati come descritto (vedi Figura 1 ). Gli aumenti e le diminuzioni dell&#39;ampiezza di EEG e EMG all&#39;insorgenza del sonno non-REM sono chiaramente visibili. Il sonno intermittente REM è segnato da una diminuzione dell&#39;ampiezza di EEG e da una ulteriore diminuzione d...

Watch this Scientific Journal Video about Quantifying Infra-slow Dynamics of Spectral Power and Heart Rate in Sleeping Mice at JoVE.com

Quantifying Infra-slow Dynamics of Spectral Power and Heart Rate in Sleeping Mice

Qui presentiamo procedure sperimentali e analitiche per descrivere le dinamiche temporali delle variabili neurali e cardiache del sonno non REM nei topi, che modulano la risposta al sonno agli stimoli acustici.

Quantificare la dinamica infrarosso del potere spettrale e della frequenza cardiaca nei topi addormentati

Three vigilance states dominate mammalian life: wakefulness, non-rapid eye movement (non-REM) sleep, and REM sleep. As more neural correlates of behavior ...

quantifying-infra-slow-dynamics-spectral-power-heart-rate-sleeping

Research

JoVE Journal

Neuroscience

9.9K Views.  University of Lausanne.  Qui presentiamo procedure sperimentali e analitiche per descrivere le dinamiche temporali delle variabili neurali e cardiache del sonno non REM nei topi, che modulano la risposta al sonno agli stimoli acustici. 

Video: Quantifying Infra-slow Dynamics of Spectral Power and Heart Rate in Sleeping Mice

Simultaneous Video-EEG-ECG Monitoring to Identify Neurocardiac Dysfunction in Mouse Models of Epilepsy

In epilepsy, seizures can evoke cardiac rhythm disturbances such as heart rate changes, conduction blocks, asystoles, and arrhythmias, which can potentially increase risk of sudden unexpected death in epilepsy (SUDEP). Electroencephalography (EEG) and electrocardiography (ECG) are widely used clinical diagnostic tools to monitor for abnormal brain and cardiac rhythms in patients. Here, a technique to simultaneously record video, EEG, and ECG in mice to measure behavior, brain, and cardiac activities, respectively, is described. The technique described herein utilizes a tethered (i.e., wired) recording configuration in which the implanted electrode on the head of the mouse is hard-wired to the recording equipment. Compared to wireless telemetry recording systems, the tethered arrangement possesses several technical advantages such as a greater possible number of channels for recording EEG or other biopotentials; lower electrode costs; and greater frequency bandwidth (i.e., sampling rate) of recordings. The basics of this technique can also be easily modified to accommodate recording other biosignals, such as electromyography (EMG) or plethysmography for assessment of muscle and respiratory activity, respectively. In addition to describing how to perform the EEG-ECG recordings, we also detail methods to quantify the resulting data for seizures, EEG spectral power, cardiac function, and heart rate variability, which we demonstrate in an example experiment using a mouse with epilepsy due to Kcna1 gene deletion. Video-EEG-ECG monitoring in mouse models of epilepsy or other neurological disease provides a powerful tool to identify dysfunction at the level of the brain, heart, or brain-heart interactions.

Here, we present a protocol to record brain and heart bio signals in mice using simultaneous video, electroencephalography (EEG), and electrocardiography (ECG). We also describe methods to analyze the resulting EEG-ECG recordings for seizures, EEG spectral power, cardiac function, and heart rate variability.

Video-EEG-ECG simultaneo monitoraggio per identificare la disfunzione Neurocardiac in modelli murini di epilessia

In epilepsy, seizures can evoke cardiac rhythm disturbances such as heart rate changes, conduction blocks, asystoles, and arrhythmias, which can ...

Ricerca

Genetica

Implantation of Radiotelemetry Transmitters Yielding Data on ECG, Heart Rate, Core Body Temperature and Activity in Free-moving Laboratory Mice

The laboratory mouse is the animal species of choice for most biomedical research, in both the academic sphere and the pharmaceutical industry. Mice are a manageable size and relatively easy to house. These factors, together with the availability of a wealth of spontaneous and experimentally induced mutants, make laboratory mice ideally suited to a wide variety of research areas.
In cardiovascular, pharmacological and toxicological research, accurate measurement of parameters relating to the circulatory system of laboratory animals is often required. Determination of heart rate, heart rate variability, and duration of PQ and QT intervals are based on electrocardiogram (ECG) recordings. However, obtaining reliable ECG curves as well as physiological data such as core body temperature in mice can be difficult using conventional measurement techniques, which require connecting sensors and lead wires to a restrained, tethered, or even anaesthetized animal. Data obtained in this fashion must be interpreted with caution, as it is well known that restraining and anesthesia can have a major artifactual influence on physiological parameters1, 2.
Radiotelemetry enables data to be collected from conscious and untethered animals. Measurements can be conducted even in freely moving animals, and without requiring the investigator to be in the proximity of the animal. Thus, known sources of artifacts are avoided, and accurate and reliable measurements are assured. This methodology also reduces interanimal variability, thus reducing the number of animals used, rendering this technology the most humane method of monitoring physiological parameters in laboratory animals3, 4. Constant advancements in data acquisition technology and implant miniaturization mean that it is now possible to record physiological parameters and locomotor activity continuously and in realtime over longer periods such as hours, days or even weeks3, 5.
Here, we describe a surgical technique for implantation of a commercially available telemetry transmitter used for continuous measurements of core body temperature, locomotor activity and biopotential (i.e. onelead ECG), from which heart rate, heart rate variability, and PQ and QT intervals can be established in freeroaming, untethered mice. We also present pre-operative procedures and protocols for post-operative intensive care and pain treatment that improve recovery, well-being and survival rates in implanted mice5, 6.

A surgical technique for implantation of commercially available telemetry transmitters used for continuous measurement of biopotential (one-lead ECG), heart rate, core body temperature and locomotor activity in freely moving mice is shown. Recommendations and protocols for post-operative care and pain relief, improving recovery, well being and survival rate are also presented.

L&#39;impianto di trasmettitori Radiotelemetry Cedendo dati su ECG, frequenza cardiaca, temperatura corporea e attività di movimento libero topi di laboratorio

The laboratory mouse is the animal species of choice for most biomedical research, in both the academic sphere and the pharmaceutical industry. Mice are a ...

Medicina

Noninvasive, High-throughput Determination of Sleep Duration in Rodents

Traditionally, sleep is monitored by an electroencephalogram (EEG). EEG studies in rodents require surgical implantation of the electrodes followed by a long recovery period. To perform an EEG recording, the animal is connected to a receiver, creating an unnatural tether to the head-mount. EEG monitoring is time consuming, carries risk to the animal, and is not a completely natural setting for the measurement of sleep. Alternative methods to detect sleep, particularly in a high-throughput fashion, would greatly advance the field of sleep research. Here, we describe a validated method for detecting sleep via activity-based home-cage monitoring. Previous studies have shown that sleep assessed via this method has a high degree of agreement with sleep defined by traditional EEG-based measures. Whereas this method is validated for total sleep time, it is important to note that sleep bout duration should be assessed by an EEG which has better temporal resolution. The EEG can also differentiate rapid eye movement (REM) and non-REM sleep, giving more detail about the exact nature of sleep. Nevertheless, activity-based sleep determination can be used to analyze multiple days of undisturbed sleep and to assess sleep as a response to an acute event (like stress). Here, we show the power of this system to detect the response of mice to daily intraperitoneal injections.

We describe a high-throughput method of measuring sleep by means of activity-based home-cage monitoring. This method offers advantages over traditional EEG-based methods. It is well validated for the determination of total sleep duration and can be a powerful tool to monitor sleep in rodent models of human disease.

Determinazione non invasiva, High-throughput di durata di sonno in roditori

Traditionally, sleep is monitored by an electroencephalogram (EEG). EEG studies in rodents require surgical implantation of the electrodes followed by a ...

Comportamento

Real-Time Proxy-Control of Re-Parameterized Peripheral Signals using a Close-Loop Interface

The fields that develop methods for sensory substitution and sensory augmentation have aimed to control external goals using signals from the central nervous systems (CNS). Less frequent however, are protocols that update external signals self-generated by interactive bodies in motion. There is a paucity of methods that combine the body-heart-brain biorhythms of one moving agent to steer those of another moving agent during dyadic exchange. Part of the challenge to accomplish such a feat has been the complexity of the setup using multimodal bio-signals with different physical units, disparate time scales and variable sampling frequencies.
In recent years, the advent of wearable bio-sensors that can non-invasively harness multiple signals in tandem, has opened the possibility to re-parameterize and update the peripheral signals of interacting dyads, in addition to improving brain- and/or body-machine interfaces. Here we present a co-adaptive interface that updates efferent somatic-motor output (including kinematics and heart rate) using biosensors; parameterizes the stochastic bio-signals, sonifies this output, and feeds it back in re-parameterized form as visuo/audio-kinesthetic reafferent input. We illustrate the methods using two types of interactions, one involving two humans and another involving a human and its avatar interacting in near real time. We discuss the new methods in the context of possible new ways to measure the influences of external input on internal somatic-sensory-motor control.

We present protocols and methods of analyses to build co-adaptive interfaces that stream, parameterize, analyze, and modify human body and heart signals in close-loop. This setup interfaces signals derived from the peripheral and central nervous systems of the person with external sensory inputs to help track biophysical change.

Controllo proxy in tempo reale dei segnali periferici rimizionati utilizzando un'interfaccia a circuito chiuso

The fields that develop methods for sensory substitution and sensory augmentation have aimed to control external goals using signals from the central ...

Polygraphic Recording Procedure for Measuring Sleep in Mice

Recording of the epidural electroencephalogram (EEG) and electromyogram (EMG) in small animals, like mice and rats, has been pivotal to study the homeodynamics and circuitry of sleep-wake regulation. In many laboratories, a cable-based sleep recording system is used to monitor the EEG and EMG in freely behaving mice in combination with computer software for automatic scoring of the vigilance states on the basis of power spectrum analysis of EEG data. A description of this system is detailed herein. Steel screws are implanted over the frontal cortical area and the parietal area of 1 hemisphere for monitoring EEG signals. In addition, EMG activity is monitored by the bilateral placement of wires in both neck muscles. Non-rapid eye movement (Non-REM; NREM) sleep is characterized by large, slow brain waves with delta activity below 4 Hz in the EEG, whereas a shift from low-frequency delta activity to a rapid low-voltage EEG in the theta range between 6 and 10 Hz can be observed at the transition from NREM to REM sleep. By contrast, wakefulness is identified by low- to moderate-voltage brain waves in the EEG trace and significant EMG activity.

The recording of electroencephalogram (EEG) and electromyogram (EMG) in freely behaving mice is a critical step to correlate behavior and physiology with sleep and wakefulness. The experimental protocol described herein provides a cable-based system for acquiring EEG and EMG recordings in mice.

Procedura di registrazione poligrafica per la misurazione del sonno nei topi

Recording of the epidural electroencephalogram (EEG) and electromyogram (EMG) in small animals, like mice and rats, has been pivotal to study the ...

Neuroscienze

Novel Approach for Simultaneous Recording of Renal Sympathetic Nerve Activity and Blood Pressure with Intravenous Infusion in Conscious, Unrestrained Mice.

Renal sympathetic nerves contribute significantly to both physiological and pathophysiological phenomena. Evaluating renal sympathetic nerve activity (RSNA) is of great interest in many areas of research such as chronic kidney disease, hypertension, heart failure, diabetes and obesity. Unequivocal assessment of the role of the sympathetic nervous system is thus imperative for proper interpretation of experimental results and understanding of disease processes. RSNA has been traditionally measured in anesthetized rodents, including mice. However, mice usually exhibit very low systemic blood pressure and hemodynamic instability for several hours during anesthesia and surgery. Meaningful interpretation of RSNA is confounded by this non-physiological state, given the intimate relationship between sympathetic nervous tone and cardiovascular status. To address this limitation of traditional approaches, we developed a new method for measuring RSNA in conscious, freely-moving mice. Mice were chronically instrumented with radio-telemeters for continuous monitoring of blood pressure as well as a jugular venous infusion catheter and custom-designed bipolar electrode for direct recording of RSNA. Following a 48-72 hour recovery period, survival rate was 100% and all mice behaved normally. At this time-point, RSNA was successfully recorded in 80% of mice, with viable signals acquired up to 4 and 5 days post-surgery in 70% and 50% of mice, respectively. Physiological blood pressures were recorded in all mice (116&plusmn;2 mmHg; n=10). Recorded RSNA increased with eating and grooming, as well-established in the literature. Furthermore, RSNA was validated by ganglionic blockade and modulation of blood pressure with pharmacological agents. Herein, an effective and manageable method for clear recording of RSNA in conscious, freely-moving mice is described.

Anesthetized mice exhibit non-physiological systemic blood pressure, which precludes meaningful assessment of autonomic tone given the intimate relationship between blood pressure and the autonomic nervous system. Thus, a novel method to simultaneously record renal sympathetic nerve activity and blood pressure with intravenous infusion in conscious mice is outlined.

Nuovo approccio per la registrazione simultanea di attività simpatica renale del nervo e pressione del sangue con l'infusione endovenosa in consapevole, topi sfrenati.

Renal sympathetic nerves contribute significantly to both physiological and pathophysiological phenomena. Evaluating renal sympathetic nerve activity ...

Echocardiographic and Histological Examination of Cardiac Morphology in the Mouse

An increasing number of genetically modified mouse models has become available in recent years. Moreover, the number of pharmacological studies performed in mice is high. Phenotypic characterization of these mouse models also requires the examination of cardiac function and morphology. Echocardiography and magnetic resonance imaging (MRI) are commonly used approaches to characterize cardiac function and morphology in mice. Echocardiographic and MRI equipment specialized for use in small rodents is&#160;expensive and requires a dedicated space. This protocol describes cardiac measurements in mice using a clinical echocardiographic system with a 15 MHz human vascular probe. Measurements are performed on anesthetized adult mice. At least three image sequences are recorded and analyzed for each animal in M-mode in the parasternal short-axis view. Afterwards, cardiac histological examination is performed, and cardiomyocyte diameters are determined on hematoxylin-eosin- or wheat germ agglutinin (WGA)-stained paraffin sections. Vessel density is determined morphometrically after Pecam-1 immunostaining. The protocol has been applied successfully to pharmacological studies and different genetic animal models under baseline conditions, as well as after experimental myocardial infarction by the permanent ligation of the left anterior descending coronary artery (LAD). In our experience, echocardiographic investigation is limited to anesthetized animals and is feasible in adult mice weighing at least 25 g.

Echocardiographic examination is frequently used in mice. Expensive high-resolution ultrasound devices have been developed for this purpose. This protocol describes an affordable echocardiographic procedure combined with histological morphometric analyses to determine cardiac morphology.

Esame ecocardiografico ed istologico della morfologia cardiaca nel topo

An increasing number of genetically modified mouse models has become available in recent years. Moreover, the number of pharmacological studies performed ...

Echocardiographic Measurement of Right Ventricular Diastolic Parameters in Mouse

Diastolic dysfunction is a prominent feature of right ventricular (RV) remodeling associated with conditions of pressure overload. However, the RV diastolic function is rarely quantified in experimental studies. This might be due to technical difficulties in the visualization of the RV in the apical four-chamber view in rodents. Here we describe two positions facilitating the visualization of the apical four-chamber view in mice to assess the RV diastolic function.
The apical four-chamber view is enabled by tilting the mouse fixation platform to the left and caudally (LeCa) or to the right and cranially (RiCr). Both positions provide images of comparable quality. The results of the RV diastolic function obtained from two positions are not significantly different. Both positions are comparably easy to perform. This protocol can be incorporated into published protocols and enables detailed investigations of the RV function.

Here we describe and compare two positions for obtaining the apical four-chamber view in mice. These positions enable the quantification of the right ventricular function, provide comparable results, and can be used interchangeably.

Misurazione ecocardiografica dei parametri diastolici ventricolari a destra nel mouse

Diastolic dysfunction is a prominent feature of right ventricular (RV) remodeling associated with conditions of pressure overload. However, the RV ...

Computer-based Multitaper Spectrogram Program for Electroencephalographic Data

Current web resources provide limited, user friendly tools to compute spectrograms for visualizing and quantifying electroencephalographic (EEG) data. This paper describes a Windows-based, open source code for creating EEG multitaper spectrograms. The compiled program is accessible to Windows users without software licensing. For Macintosh users, the program is limited to those with a MATLAB software license. The program is illustrated via EEG spectrograms that vary as a function of states of sleep and wakefulness, and opiate-induced alterations in those states. The EEGs of C57BL/6J mice were wirelessly recorded for 4 h after intraperitoneal injection of saline (vehicle control) and antinociceptive doses of morphine, buprenorphine, and fentanyl. Spectrograms showed that buprenorphine and morphine caused similar changes in EEG power at 1&#8722;3 Hz and 8&#8722;9 Hz. Spectrograms after administration of fentanyl revealed maximal average power bands at 3 Hz and 7 Hz. The spectrograms unmasked differential opiate effects on EEG frequency and power. These computer-based methods are generalizable across drug classes and can be readily modified to quantify and display a wide range of rhythmic biological signals.

This protocol provides an open source, compiled MATLAB program that generates multitaper spectrograms for electroencephalographic data.

Programma spettrogramma multitaper basato su computer per dati elettroencefalografici

Current web resources provide limited, user friendly tools to compute spectrograms for visualizing and quantifying electroencephalographic (EEG) data. ...

Implantation of Combined Telemetric ECG and Blood Pressure Transmitters to Determine Spontaneous Baroreflex Sensitivity in Conscious Mice

Blood pressure (BP) and heart rate (HR) are both controlled by the autonomic nervous system (ANS) and are closely intertwined due to reflex mechanisms. The baroreflex is a key homeostatic mechanism to counteract acute, short-term changes in arterial BP and to maintain BP in a relatively narrow physiological range. BP is sensed by baroreceptors located in the aortic arch and carotid sinus. When BP changes, signals are transmitted to the central nervous system and are then communicated to the parasympathetic and sympathetic branches of the autonomic nervous system to adjust HR. A rise in BP causes a reflex decrease in HR, a drop in BP causes a reflex increase in HR.
Baroreflex sensitivity (BRS) is the quantitative relationship between changes in arterial BP and corresponding changes in HR. Cardiovascular diseases are often associated with impaired baroreflex function. In various studies reduced BRS has been reported in e.g., heart failure, myocardial infarction, or coronary artery disease. 
Determination of BRS requires information from both BP and HR, which can be recorded simultaneously using telemetric devices. The surgical procedure is described beginning with the insertion of the pressure sensor into the left carotid artery and positioning of its tip in the aortic arch to monitor arterial pressure followed by the subcutaneous placement of the transmitter and ECG electrodes. We also describe postoperative intensive care and analgesic management. After a two-week period of post-surgery recovery long-term ECG and BP recordings are performed in conscious and unrestrained mice. Finally, we include examples of high-quality recordings and the analysis of spontaneous baroreceptor sensitivity using the sequence method.

The baroreflex is a heart-rate regulation mechanism by the autonomic nervous system in response to blood-pressure changes. We describe a surgical technique to implant telemetry transmitters for continuous and simultaneous measurement of electrocardiogram and blood pressure in mice. This can determine spontaneous baroreflex sensitivity, an important prognostic marker for cardiovascular disease.

Impianto combinato di ECG telemetrico e trasmettitori di pressione sanguigna per determinare la sensibilità baroriflessa spontanea in topi coscienti

Blood pressure (BP) and heart rate (HR) are both controlled by the autonomic nervous system (ANS) and are closely intertwined due to reflex mechanisms. ...