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Phase-amplitude cross-frequency coupling in rats olfactory bulb after injection of ketamine

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Jurkiewicz G. , Hunt M. J. , Zygierewicz J.

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nr Suppl.1

EN

INTRODUCTION: The injection of ketamine is an animal model of schizophrenia. It leads to behavioral changes such as hyperlocomotion and accelerated breath and electrophysiological changes such as the appearance of high‑frequency oscillations (HFO). Previous studies reported that the amplitude of HFO in the striatum is coupled with a phase of respiratory rhythm. However, recent studies suggest that the olfactory bulb is an important generator of HFO which can impose this activity in ventral striatal areas. AIM(S): The purpose of this study was to examine the LFP recording from olfactory bulb after injection of ketamine with a novel method of phase-amplitude coupling detection. METHOD(S): The proposed novel method of PAC detection is based on analysis of time‑frequency representation of signals aligned to a given phase in the low‑frequency band. Low‑frequency wave is obtained with the Matching Pursuit algorithm by selecting waveforms of interest. The time‑frequency representation of the signal’s energy density is derived from continuous wavelet transform and normalized at each frequency relative to its average value in the baseline period. Next, the representation is thresholded at values obtained from surrogate data. The resulting maps are used to compute comodulograms. The effects presented in the comodulograms are validated with extreme values statistics. RESULTS: We found statistically significant coupling between the amplitude of high‑frequency oscillation (around 150 Hz) and phase of low‑frequency oscillation (around 7 Hz) in most of the examined rats. The temporal pattern of PAC shows dependence on injection of ketamine. CONCLUSIONS: The HFO in olfactory bulb display the property of phase-amplitude coupling with low-frequency oscillation. The additional conclusion is that the proposed novel method is adequate to detect coupling in real LFP data.

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How to write an effective response letter to reviewers

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Hunt M. J. , Ochmanska M. , Cilulko-Dolega J.

Medical Science Pulse

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2019

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tom 13

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nr 1

EN

The review process is intended to provide an objective assessment of the suitability of a submission to the target journal. When authors receive the decision letter from the editor it is almost always accompanied with the reviews, which at times can be quite critical. Writing a well-constructed response letter to the reviewers, with well-reasoned arguments, is a key part of the reviewing process. Although the manuscript is the main focus of the submission, the content and tone of the response letter can have a surprisingly large impact on the eventual recommendation given by the reviewers. The importance of writing a clear response letter is often overlooked by authors. This prompted us to prepare a short article addressing the main points that can help authors prepare their response to reviewer letter to the reviewers. Although each review is unique, here, we outline ten points which are aimed at helping authors respond effectively and clearly to reviewers’ comments. The points are based on the authors’ collective experiences which includes publishing and reviewing for international peer-reviewed journals. The tone of the letter should always be professional, organized and objective. Each point raised by the reviewers needs to be replied to in a precise way, with clear evidence that the major concerns have been considered in a serious way. This article also covers what information should be included, when it is appropriate to disagree with a reviewer, and how to present appropriate rebuttals.

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Nasal respiration is critical for ketamine induced high frequency oscillations and hyperactivity

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Wrobel J. J. , Sredniawa W. , Wojcik D. K. , Hunt M. J.

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nr Suppl.1

EN

INTRODUCTION: Ketamine, at subanesthetic doses, produces psychotomimetic effects. In rodents, ketamine produces characteristic changes in oscillatory activity that can be recorded in local field potentials (LFP). One effect after systemic injection of ketamine is the emergence of abnormal high frequency oscillations (HFO) 130 ‑180 Hz that have been described in many rodent brain areas. Recently, we have shown that the olfactory bulb (OB) plays an important role in the generation of HFO after ketamine. AIM(S): The aim of the present study was to examine the extent to which nasal respiration may drive abnormal HFO after ketamine, in freely‑moving rats. METHOD(S): LFPs (from the OB) and nasal respiration (thermocouples implanted in the nares) were recorded before and after injection (saline or ketamine 20 mg/kg) from male Wistar rats. A separate group of rats was used to study nares blockade. To block the nares, rats were anesthetised and a silicon occluder was inserted into one or both nares. Controls were exposed to initial isoflurane for a comparable amount of time but without blockade. Rats were given recovery and then injected with ketamine. RESULTS: Ketamine immediately increased exploratory fast sniffing (4‑10 Hz), which correlated with increases in locomotor activity and HFO power. Saline injection did not substantially alter these measures. Nasal respiration entrained bursts of ketamine HFO recorded in the OB on a cycle‑by‑cycle basis. Further, ketamine-induced HFO was attenuated unilaterally by naris blockade on the same side. Bilateral naris blockade reduced power and frequency of HFO and also reduced hyperactivity produced by ketamine. CONCLUSIONS: Our results suggest that nasal respiration is a powerful drive of HFO after injection of ketamine in the OB. These findings may explain previous observations that ketamine-HFO couples to slower frequencies. Functional nasal respiration appears to be critical for the emergence of both HFO and hyperactivity produced by ketamine.

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Local blockade of NMDA receptors in the rat prefrontal cortex increases c_Fos expression in multiple subcortical regions

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Nowak K. , Meyza K. , Nikolaev E. , Hunt M. J. , Kasicki S.

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nr 3

EN

Ketamine, phencyclidine and MK801 are uncompetitive NMDA receptor (NMDAR) antagonists which are used widely to model certain features of schizophrenia in rats. Systemic administration of NMDAR antagonists, in addition to provoking an increase in c-Fos expression, leads to important neurochemical and electrophysiological changes within the medial prefrontal cortex (mPFC). Since the mPFC is considered to exert a top-down regulatory control of subcortical brain regions, we examined the effects of local infusion of the NMDAR antagonist, MK801, into the mPFC on the expression of c-Fos protein (widely used marker of neuronal activation) in several subcortical structures. The experiment was performed on freely moving rats, bilaterally implanted with guide cannulae in the prelimbic mPFC, infused with MK801 or saline. Bilateral administration of MK801 to the mPFC produced changes in the behavior (increased stereotypy and decreased sleep-like behavior) and complex changes in c-Fos protein expression with significant increases observed in the nucleus accumbens (core and shell), amygdala (basolateral and central nuclei), the CA1 field of the hippocampus, and mediodorsal and paraventricular thalamic nuclei, as compared to the saline group. Together, we demonstrate that blockade of NMDA receptors in the mPFC is sufficient to lead to behavioral abnormalities and increased c-Fos expression in many, but not all, of the subcortical structures examined. Our findings suggest that some of the behavioral abnormalities produced by uncompetitive NMDAR antagonists may result from aberrant activity in cortico-subcortical pathways. These data support an increasing body of literature, suggesting that the mPFC is an important site mediating the effects of NMDAR antagonists.

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How to write a good abstract for a biomedical paper

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Hunt M. J. , Raflik K. , Wesolowski D. , Sibilska-Wozniacka A. , Sakowska-Hunt D. E.

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nr 1

EN

Although a relatively short text, the abstract of a paper summarizes the most important issues raised in the main text. The abstract is, at least initially, the key text on which journal editors, reviewers and eventually readers form their initial judgement on the overall quality of the full manuscript. Therefore, it is essential to execute this step of the writing process well. In this article, we discuss the purpose of an abstract, why it is important, and how to write a good abstract. Increasingly, journal abstracts are structured to follow the IMRAD format (Introduction, Methods, Results, and Discussion). We provide examples of well written and badly written abstracts, with explanatory notes, to help readers understand the key points that need to be addressed and mistakes that should be avoided. Since international abstracts are generally written in English, preparing an abstract can be especially challenging for researchers who are not native speakers of English. We close this article with general linguistic advice, paying particular attention to key terms and word choice than can meaningfully express an author’s intention in a concise way. The points raised in this article will help authors improve their scientific writing and enable their findings to be expressed with clarity.