investigating-motor-skill-learning-processes-with-robotic

Investigating Motor Skill Learning Processes with a Robotic Manipulandum

Skilled reaching tasks are commonly used in studies of motor skill learning and motor function under healthy and pathological conditions, but can be ...

University Hospital Zurich

Mounting evidence suggests that sleep loss negatively affects learning and memory processes through disruption of hippocampal function. In the present study, we examined whether sleep loss alters the generation, differentiation, and survival of new cells in the dentate gyrus. Rats were sleep restricted by keeping them awake in slowly rotating drums for 1 day or repeatedly for 20 h/day over a period of 8 days. In addition to home cage controls, we included forced activity controls which, compared to sleep restricted rats, walked at double speed for half the time. These animals thus walked the same distance but had sufficient time to sleep. The results show that a single day of sleep deprivation significantly reduced hippocampal cell proliferation in the hilus of the dentate gyrus as measured by immunostaining for the proliferation marker Ki-67. Repeated partial sleep deprivation reduced cell proliferation in both the hilus and the subgranular zone. However, the latter was also found after chronic forced activity, and may not have been specific for sleep loss. To study neuronal survival, rats received a single intraperitoneal injection of 5-bromo-2'-deoxyuridine (BrdU) 5 days before the experiment. The number of surviving, BrdU-positive cells was not affected by sleep restriction. Also, the differentiation of BrdU-positive new cells into NeuN-positive neuronal and GFAP-positive glial phenotypes was not significantly altered by sleep loss. In conclusion, since new cells in the hilus mostly differentiate into glia, our findings indicate that sleep loss may reduce hippocampal gliogenesis.

Sleep restriction by forced activity reduces hippocampal cell proliferation.

Montage des &eacute;l&eacute;ments de preuve donne &agrave; penser que la perte de sommeil affecte n&eacute;gativement l&#39;apprentissage et les processus de m&eacute;moire par l&#39;interruption de la fonction de l&#39;hippocampe. Dans la pr&eacute;sente &eacute;tude, nous avons examin&eacute; si la perte de sommeil alt&egrave;re la g&eacute;n&eacute;ration, la diff&eacute;renciation et la survie de nouvelles cellules dans le gyrus dent&eacute;. Des rats ont sommeil restreint en les gardant &eacute;veill&eacute; en tournant lentement les tambours pour 1 jour ou plusieurs fois pendant 20 heures par jour sur une p&eacute;riode de 8 jours. Outre les contr&ocirc;les de cage maison, nous avons inclus des contr&ocirc;les d&#39;activit&eacute; forc&eacute;e qui, par rapport aux rats restreints, marchais &agrave; double vitesse pour la moiti&eacute; du temps de sommeil. Ces animaux ont ainsi parcouru la m&ecirc;me distance mais eu suffisamment de temps pour dormir. Les r&eacute;sultats montrent qu&#39;un seul jour de privation de sommeil r&eacute;duit significativement la prolif&eacute;ration des cellules hippocampiques dans le hile du gyrus dent&eacute; mesur&eacute;e par immunomarquage pour le marqueur de prolif&eacute;ration Ki-67. Manque de sommeil partielles r&eacute;p&eacute;t&eacute;es r&eacute;duit la prolif&eacute;ration des cellules &agrave; la fois le hile et la zone subgranulaire. Toutefois, ce dernier a &eacute;t&eacute; &eacute;galement constat&eacute; apr&egrave;s chronique activit&eacute; forc&eacute;e et n&#39;ont pas pu sp&eacute;cifique pour la perte de sommeil. Pour &eacute;tudier la survie des neurones, des rats ont re&ccedil;u une seule injection intrap&eacute;riton&eacute;ale de 5-bromo-2&#39;-deoxyuridine (BrdU) 5 jours avant l&#39;exp&eacute;rience. Le nombre de cellules survivantes, BrdU positif n&#39;est pas affect&eacute; par la restriction de sommeil. En outre, la diff&eacute;renciation de cellules nouvelles BrdU positives en NeuN-positif neuronale et ph&eacute;notypes gliales GFAP-positive n&#39;a pas &eacute;t&eacute; significativement modifi&eacute;e par la perte de sommeil. En conclusion, &eacute;tant donn&eacute; que pour la plupart, nouvelles cellules dans le hile se diff&eacute;rencient en cellules gliales, nos r&eacute;sultats indiquent que la perte de sommeil peut r&eacute;duire gliogenesis hippocampe.

Restriction de sommeil par activit&eacute; forc&eacute;e r&eacute;duit la prolif&eacute;ration des cellules hippocampiques.

Prove di montaggio suggerisce che perdita di sonno influisce negativamente apprendimento e dei processi di memoria attraverso l&#39;alterazione della funzione dell&#39;ippocampo. Nel presente studio, abbiamo esaminato se la perdita di sonno altera la generazione, la differenziazione e la sopravvivenza di nuove cellule del giro dentato. Ratti sono stati sonno limitato di tenerli svegli in lentamente rotanti batteria per 1 giorno o pi&ugrave; volte per 20 ore al giorno per un periodo di 8 giorni. Oltre ai controlli domestici gabbia, abbiamo incluso controlli attivit&agrave; forzata che, rispetto ai ratti limitati, camminati a velocit&agrave; doppia per met&agrave; del tempo di sonno. Questi animali cos&igrave; camminato alla stessa distanza ma ha avuto il tempo sufficiente per dormire. I risultati mostrano che un solo giorno di privazione del sonno significativamente ridotta proliferazione delle cellule dell&#39;ippocampo nel hilus del giro dentato come misurato da immunocolorazione per il marcatore di proliferazione Ki-67. Privazione del sonno parziale ripetute ridotta proliferazione cellulare hilus sia la SGZ. Tuttavia, quest&#39;ultimo &egrave; stato anche trovato dopo cronica attivit&agrave; forzata e non pu&ograve; essere stato specifico per la perdita di sonno. Per studiare la sopravvivenza neuronale, ratti hanno ricevuto una singola iniezione intraperitoneale di 5-bromo-2&#39;-deoxyuridine (BrdU) 5 giorni prima dell&#39;esperimento. Il numero di cellule sopravvissute, BrdU-positiva non &egrave; stato influenzato dalla restrizione di sonno. Inoltre, la differenziazione delle cellule nuove BrdU-positivi in positivo NeuN neuronale e fenotipi gliali GFAP-positivo non &egrave; stata alterata significativamente dalla perdita di sonno. In conclusione, poich&eacute; nuove cellule in hilus si differenziano principalmente in glia, i nostri risultati indicano che la perdita di sonno pu&ograve; ridurre gliogenesis hippocampal.

Restrizione di sonno da attivit&agrave; forzata riduce la proliferazione delle cellule dell&#39;ippocampo.

Sleep is homeostatically regulated in all animal species that have been carefully studied so far. The best characterized marker of sleep homeostasis is slow wave activity (SWA), the EEG power between 0.5 and 4 Hz during nonrapid eye movement (NREM) sleep. SWA reflects the accumulation of sleep pressure as a function of duration and/or intensity of prior wake: it increases after spontaneous wake and short-term (3-24 h) sleep deprivation and decreases during sleep. However, recent evidence suggests that during chronic sleep restriction (SR) sleep may be regulated by both allostatic and homeostatic mechanisms. Here, we performed continuous, almost completely artifact-free EEG recordings from frontal, parietal, and occipital cortex in freely moving rats (n = 11) during and after 5 d of SR. During SR, rats were allowed to sleep during the first 4 h of the light period (4S(+)) but not during the following 20 h (20S(-)). During the daily 20S(-) most sleep was prevented, whereas the number of short (<20 s) sleep attempts increased. Low-frequency EEG power (1-6 Hz) in both sleep and wake also increased during 20S(-), most notably in the occipital cortex. In all animals NREM SWA increased above baseline levels during the 4S(+) periods and in post-SR recovery. The SWA increase was more pronounced in frontal cortex, and its magnitude was determined by the efficiency of SR. Analysis of cumulative slow wave energy demonstrated that the loss of SWA during SR was compensated by the end of the second recovery day. Thus, the homeostatic regulation of sleep is preserved under conditions of chronic SR.

Sleep homeostasis in the rat is preserved during chronic sleep restriction.

Lack of compensatory or even reduced food intake is frequently observed in weight-losing cancer patients and contributes to increased morbidity and mortality. Our previous work has shown increased transcription factor expression in the hypothalamus and ventral striatum of anorectic rats bearing small tumors. mRNA expression of molecules known to be involved in pathways regulating appetite in these structures was therefore assessed in this study. Given that pain, pro-inflammatory cytokines and metabolic hormones can modify food intake, spinal cord cellular activation patterns and plasma concentrations of cytokines and hormones were also studied. Morris hepatoma 7777 cells injected subcutaneously in Buffalo rats provoked a 10% lower body weight and 15% reduction in food intake compared to free-feeding tumor-free animals 4 weeks later when the tumor represented 1-2% of body mass. No differences in spinal cord activation patterns or plasma concentration of pro-inflammatory cytokines were observed between groups. However, the changes in plasma ghrelin and leptin concentrations found in food-restricted weight-matched rats in comparison to ad libitum-fed animals did not occur in anorectic tumor-bearing animals. Real-time PCR showed that tumor-bearing rats did not display the increase in hypothalamic agouti-related peptide mRNA observed in food-restricted weight-matched animals. In addition, microarray analysis and real-time PCR revealed increased ventral striatal prostaglandin D synthase expression in food-restricted animals compared to anorectic tumor-bearing rats. These findings indicate that blunted hypothalamic AgRP mRNA expression, probably as a consequence of relatively high leptin and low ghrelin concentrations, and reduced ventral striatal prostaglandin D synthesis play a role in maintaining cancer-associated anorexia.

Hormonal, hypothalamic and striatal responses to reduced body weight gain are attenuated in anorectic rats bearing small tumors.

Neuroplasticity and reorganization of brain motor networks are thought to enable recovery of motor function after ischemic stroke. Especially in the cortex surrounding the ischemic scar (i.e., peri-infarct cortex), evidence for lasting reorganization has been found at the level of neurons and networks. This reorganization depends on expression of specific genes and subsequent protein synthesis. To test the functional relevance of the peri-infarct cortex for recovery we assessed the effect of protein synthesis inhibition within this region after experimental stroke. Long-Evans rats were trained to perform a skilled-reaching task (SRT) until they reached plateau performance. A photothrombotic stroke was induced in the forelimb representation of the primary motor cortex (M1) contralateral to the trained paw. The SRT was re-trained after stroke while the protein synthesis inhibitor anisomycin (ANI) or saline were injected into the peri-infarct cortex through implanted cannulas. ANI injections reduced protein synthesis within the peri-infarct cortex by 69% and significantly impaired recovery of reaching performance through re-training. Improvement of motor performance within a single training session remained intact, while improvement between training sessions was impaired. ANI injections did not affect infarct size. Thus, protein synthesis inhibition within the peri-infarct cortex impairs recovery of motor deficits after ischemic stroke by interfering with consolidation of motor memory between training sessions but not short-term improvements within one session.

Article	Year
Sleep restriction by forced activity reduces hippocampal cell proliferation. Brain research\| PubMed ID: 16309630	2005
Sleep homeostasis in the rat is preserved during chronic sleep restriction. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 20696898	2010
Hormonal, hypothalamic and striatal responses to reduced body weight gain are attenuated in anorectic rats bearing small tumors. Brain, behavior, and immunity\| PubMed ID: 21334429	2011
Protein Synthesis Inhibition in the Peri-Infarct Cortex Slows Motor Recovery in Rats. PloS one\| PubMed ID: 27314672	2016

Susan Leemburg

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