New insights from 22-kHz ultrasonic vocalizations to characterize fear responses: relationship with respiration and brain oscillatory dynamics

Fear behavior depends on interactions between the medial prefrontal cortex (mPFC) and the basolateral amygdala (BLA), and the expression of fear involves synchronized activity in theta and gamma oscillatory activities. In addition, freezing, the most classical measure of fear response in rodents, temporally coincides with the development of sustained 4-Hz oscillations in prefrontal-amygdala circuits. Interestingly, these oscillations were recently shown to depend on the animal's respiratory rhythm, supporting the growing body of evidence pinpointing the influence of nasal breathing on brain rhythms. During fearful states, rats also emit 22-kHz ultrasonic vocalizations (USV) which drastically affect respiratory rhythm. However, the relationship between 22-kHz USV, respiration and brain oscillatory activities is still unknown. Yet such information is crucial for a comprehensive understanding of how the different components of fear response collectively modulate rat's brain neural dynamics. Here we trained male rats in an odor fear conditioning task, while recording simultaneously local field potentials in BLA, mPFC and olfactory piriform cortex, together with USV calls and respiration. We show that USV calls coincide with an increase in delta and gamma power and a decrease in theta power. In addition, during USV emission in contrast to silent freezing, there is no coupling between respiratory rate and delta frequency, and the modulation of fast oscillations amplitude relative to the phase of respiration is modified. We propose that sequences of USV calls could result in a differential gating of information within the network of structures sustaining fear behavior, thus potentially modulating fear expression/memory. Significance Statement: While freezing is the most frequently used measure of fear, it is only one amongst the different components of rodents' response to threatening events. USV is another index that gives additional insight into the socioemotional status of an individual. Our study is the first to describe the effects of USV production on rat's brain oscillatory activities in the fear neural network, and to relate some of them to changes in nasal breathing. A better knowledge of the impact of USV calls on brain neural dynamics is not only important for understanding the respective weight of the different components of fear response, but is also particularly relevant for rodent models of human neuropsychiatric disorders, for which socio-affective communication is severely impaired.

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Respiration and brain neural dynamics associated with interval timing during odor fear learning in rats

10.1101/2020.07.31.228866 ◽

2020 ◽

Author(s):

Maryne Dupin ◽

Samuel Garcia ◽

Belkacem Messaoudi ◽

Valérie Doyère ◽

Anne-Marie Mouly

Keyword(s):

Fear Conditioning ◽

Basolateral Amygdala ◽

Piriform Cortex ◽

Respiratory Rhythm ◽

Interval Timing ◽

Fear Learning ◽

Gamma Activity ◽

Time Interval ◽

Scalar Property ◽

Learned Fear

ABSTRACTIn fear conditioning, where a conditioned stimulus predicts the arrival of an aversive stimulus, the animal encodes the time interval between the two stimuli. Freezing, the most used index to assess learned fear, lacks the temporal resolution required to investigate interval timing at the early stages of learning. Here we monitored respiration to visualize anticipatory behavioral responses in an odor fear conditioning in rats, while recording theta (5-15Hz) and gamma (40-80Hz) brain oscillatory activities in the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), dorsomedial striatum (DMS) and olfactory piriform cortex (PIR). We investigated the temporal patterns of respiration frequency and of theta and gamma activity power during the odor-shock interval. We found that akin to respiration patterns, theta temporal curves were modulated by the duration of the odor-shock interval in the four recording sites, and respected scalar property in mPFC and DMS. In contrast, gamma temporal curves were modulated by the interval duration only in the mPFC, and in a manner that did not respect scalar property. This suggests a preferential role for theta rhythm in interval timing. In addition, our data bring the novel idea that the respiratory rhythm might take part in the setting of theta activity dynamics.

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Ultrasonic Vocalizations Emission across Development in Rats: Coordination with Respiration and Impact on Brain Neural Dynamics

Brain Sciences ◽

10.3390/brainsci11050616 ◽

2021 ◽

Vol 11 (5) ◽

pp. 616

Author(s):

Julie Boulanger-Bertolus ◽

Anne-Marie Mouly

Keyword(s):

Cognitive Functions ◽

Brain Activity ◽

Respiratory Rhythm ◽

Emotional Memory ◽

Ultrasonic Vocalizations ◽

Neural Dynamics ◽

Adult Rats ◽

Acoustic Characteristics ◽

Memory Processes

Rats communicate using ultrasonic vocalizations (USV) throughout their life when confronted with emotionally stimulating situations, either negative or positive. The context of USV emission and the psychoacoustic characteristics of the vocalizations change greatly between infancy and adulthood. Importantly, the production of USV is tightly coordinated with respiration, and respiratory rhythm is known to influence brain activity and cognitive functions. This review goes through the acoustic characteristics and mechanisms of production of USV both in infant and adult rats and emphasizes the tight relationships that exist between USV emission and respiration throughout the rat’s development. It further describes how USV emission and respiration collectively affect brain oscillatory activities. We discuss the possible association of USV emission with emotional memory processes and point out several avenues of research on USV that are currently overlooked and could fill gaps in our knowledge.

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Respiration and brain neural dynamics associated with interval timing during odor fear learning in rats

Scientific Reports ◽

10.1038/s41598-020-74741-2 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Maryne Dupin ◽

Samuel Garcia ◽

Belkacem Messaoudi ◽

Valérie Doyère ◽

Anne-Marie Mouly

Keyword(s):

Fear Conditioning ◽

Basolateral Amygdala ◽

Piriform Cortex ◽

Respiratory Rhythm ◽

Interval Timing ◽

Fear Learning ◽

Gamma Activity ◽

Time Interval ◽

The Novel ◽

Scalar Property

Abstract In fear conditioning, where a conditioned stimulus predicts the arrival of an aversive stimulus, the animal encodes the time interval between the two stimuli. Here we monitored respiration to visualize anticipatory behavioral responses in an odor fear conditioning in rats, while recording theta (5–15 Hz) and gamma (40–80 Hz) brain oscillatory activities in the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), dorsomedial striatum (DMS) and olfactory piriform cortex (PIR). We investigated the temporal patterns of respiration frequency and of theta and gamma activity power during the odor-shock interval, comparing two interval durations. We found that akin to respiration patterns, theta temporal curves were modulated by the duration of the odor-shock interval in the four recording sites, and respected scalar property in mPFC and DMS. In contrast, gamma temporal curves were modulated by the interval duration only in the mPFC, and in a manner that did not respect scalar property. This suggests a preferential role for theta rhythm in interval timing. In addition, our data bring the novel idea that the respiratory rhythm might take part in the setting of theta activity dynamics related to timing.

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Beneficial effect of retigabine on memory in rats receiving ethanol

Pharmacological Reports ◽

10.1007/s43440-020-00205-z ◽

2020 ◽

Author(s):

Ewa Zwierzyńska ◽

Agata Krupa-Burtnik ◽

Bogusława Pietrzak

Keyword(s):

Beneficial Effect ◽

Fear Conditioning ◽

Morris Water Maze ◽

Water Maze ◽

Experimental Models ◽

Male Rats ◽

Ethanol Administration ◽

Free Access ◽

Oral Gavage ◽

The Impact

Abstract Background Retigabine belongs to the novel generation of antiepileptic drugs but its complex mechanism of action causes that the drug might be effective in other diseases, for instance, alcohol dependence. It is known that ethanol abuse impaired the function of brain structures associated with memory and learning such as the hippocampus. In our previous study, retigabine reduced hippocampal changes induced by ethanol in the EEG rhythms in rabbits. This study is focused on the impact of retigabine on memory processes in male rats receiving alcohol. Methods Memory was evaluated in various experimental models: Morris water maze, Contextual, and Cued Fear Conditioning tests. Retigabine was administered for 3 weeks directly to the stomach via oral gavage at a dose of 10 mg/kg. Rats received also 20% ethanol (5 g/kg/day in two doses) via oral gavage for 3 weeks and had free access to 5% ethanol in the afternoon and at night. Morris water maze was performed after 1 and 3 weeks of ethanol administration and after 1 week from the discontinuation of ethanol administration. Contextual and Cued Fear Conditioning tests were carried out after 24 h and 72 h of alcohol discontinuation. Results The drug significantly decreased ethanol-induced memory disturbances during alcohol administration as well as slightly improved learning processes after the discontinuation of ethanol administration. Conclusions This beneficial effect of retigabine-ethanol interaction on memory may be a relevant element of the drug’s impact on the development of addiction.

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Effects of Lacosamide Treatment on Epileptogenesis, Neuronal Damage and Behavioral Comorbidities in a Rat Model of Temporal Lobe Epilepsy

International Journal of Molecular Sciences ◽

10.3390/ijms22094667 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4667

Author(s):

Michaela Shishmanova-Doseva ◽

Dimitrinka Atanasova ◽

Yordanka Uzunova ◽

Lyubka Yoanidu ◽

Lyudmil Peychev ◽

...

Keyword(s):

Oxidative Stress ◽

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Basolateral Amygdala ◽

Neuronal Damage ◽

Piriform Cortex ◽

Preference Test ◽

Neuroprotective Activity ◽

Object Recognition Test ◽

Beneficial Effects

Clinically, temporal lobe epilepsy (TLE) is the most prevalent type of partial epilepsy and often accompanied by various comorbidities. The present study aimed to evaluate the effects of chronic treatment with the antiepileptic drug (AED) lacosamide (LCM) on spontaneous motor seizures (SMS), behavioral comorbidities, oxidative stress, neuroinflammation, and neuronal damage in a model of TLE. Vehicle/LCM treatment (30 mg/kg, p.o.) was administered 3 h after the pilocarpine-induced status epilepticus (SE) and continued for up to 12 weeks in Wistar rats. Our study showed that LCM attenuated the number of SMS and corrected comorbid to epilepsy impaired motor activity, anxiety, memory, and alleviated depressive-like responses measured in the elevated plus maze, object recognition test, radial arm maze test, and sucrose preference test, respectively. This AED suppressed oxidative stress through increased superoxide dismutase activity and glutathione levels, and alleviated catalase activity and lipid peroxidation in the hippocampus. Lacosamide treatment after SE mitigated the increased levels of IL-1β and TNF-α in the hippocampus and exerted strong neuroprotection both in the dorsal and ventral hippocampus, basolateral amygdala, and partially in the piriform cortex. Our results suggest that the antioxidant, anti-inflammatory, and neuroprotective activity of LCM is an important prerequisite for its anticonvulsant and beneficial effects on SE-induced behavioral comorbidities.

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Vulnerability factors for mephedrone-induced conditioned place preference in rats—the impact of sex differences, social-conditioning and stress

Psychopharmacology ◽

10.1007/s00213-021-05910-y ◽

2021 ◽

Author(s):

Olga Wronikowska ◽

Maria Zykubek ◽

Łukasz Kurach ◽

Agnieszka Michalak ◽

Anna Boguszewska-Czubara ◽

...

Keyword(s):

Sex Differences ◽

Conditioned Place Preference ◽

Low Dose ◽

Social Factor ◽

Place Preference ◽

Female Rats ◽

Male Rats ◽

Social Conditioning ◽

Male And Female Rats ◽

The Impact

Abstract Rationale Mephedrone is a frequently overused drug of abuse that belongs to the group of novel psychoactive substances. Although its mechanism of action, as well as toxic and psychoactive effects, has been widely studied, the role of different factors that could contribute to the increased vulnerability to mephedrone abuse is still poorly understood. Objectives The aim of the presented study was to assess the impact of several factors (sex differences, social-conditioning, and chronic mild unpredictable stress — CMUS) on the liability to mephedrone-induced reward in Wistar rats. Methods The rewarding effects of mephedrone in male and female rats were assessed using the conditioned place preference (CPP) procedure. Furthermore, the impact of social factor and stress was evaluated in male rats using social-CPP and CMUS-dependent CPP, respectively. Results Mephedrone induced classic-CPP in female (10 mg/kg), as well as in male (10 and 20 mg/kg) rats. However, the impact of mephedrone treatment during social-CPP was highly dose-dependent as the rewarding effects of low dose of mephedrone (5 mg/kg; non-active in classic-CPP) were potentiated when administered during social-conditioning. Interestingly, social-conditioning with a higher dose of 20 mg/kg (that induced classic-CPP) was able to reverse these effects. Finally, CMUS potentiated rewarding effects of a low dose of mephedrone (5 mg/kg) and increased the level of corticosterone in rats’ prefrontal cortex and hippocampus. Conclusions Altogether, the presented results give new insight into possible factors underlying the vulnerability to mephedrone abuse and can serve as a basis for further studies assessing mechanisms underlying observed effects.

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Can Sex Improve Nasal Function?—An Exploration of the Link Between Sex and Nasal Function

Ear Nose & Throat Journal ◽

10.1177/0145561320981441 ◽

2021 ◽

pp. 014556132098144

Author(s):

Olcay Cem Bulut ◽

Dare Oladokun ◽

Burkard M. Lippert ◽

Ralph Hohenberger

Keyword(s):

Sexual Activity ◽

Sexual Intercourse ◽

Nasal Obstruction ◽

Nasal Breathing ◽

Post Intervention ◽

Nasal Decongestant ◽

Symptom Evaluation ◽

Nasal Function ◽

Nasal Flow ◽

The Impact

Objectives: This study was conducted to examine the impact of sexual activity on nasal breathing and compare such effect to that of a nasal decongestant. Methods: We evaluated nasal breathing at 5 different times: (1) before sexual activity (baseline), (2) immediately after sexual activity, (3) 30 minutes, (4) 1 hour (5), and 3 hours after sexual climax. Same measurements were taken on the second day following application of nasal decongestant spray. For evaluation of nasal breathing, we used a visual analogue scale (VAS). Additionally, we used a portable rhinometric device to measure resistance and nasal flow. Results: Nasal breathing improved significantly after sexual intercourse with climax to the same degree as after application of nasal decongestant for up to 60 minutes, as measured subjectively with the VAS (sex −3.6, P < .001; spray −3.2, P < .001). This was confirmed in the objective rhinometric data as mean nasal flow (mL/s) increased while resistance decreased immediately (flow sex +214, P < .001; flow spray +235, P < .001), 30 (flow sex +249, P < .001; flow spray +287, P < .001), and 60 minutes (flow sex +180, P < .001; flow spray +287, P < .001) post-intervention. Nasal breathing was back to the baseline level after 3 hours following sexual intercourse, while it continued to be improved for longer after application of nasal decongestant. Only participants having nasal obstruction (Nasal Obstruction Symptom Evaluation score >30) showed nasal function improvement after sex. Conclusions: Sexual intercourse with climax can improve nasal breathing to the same degree as application of nasal decongestant for up to 60 minutes in patients having nasal obstruction.

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The Effect of Maternal Immune Activation on Social Play-Induced Ultrasonic Vocalization in Rats

Brain Sciences ◽

10.3390/brainsci11030344 ◽

2021 ◽

Vol 11 (3) ◽

pp. 344

Author(s):

Kinga Gzielo ◽

Agnieszka Potasiewicz ◽

Ewa Litwa ◽

Diana Piotrowska ◽

Piotr Popik ◽

...

Keyword(s):

Immune Activation ◽

Social Play ◽

Autism Spectrum ◽

Repetitive Behaviors ◽

Male Rats ◽

Poly I:C ◽

Maternal Immune Activation ◽

Increased Risk ◽

Adolescent Rats ◽

The Impact

Prenatal maternal infection is associated with an increased risk of various neurodevelopmental disorders, including autism spectrum disorders (ASD). Maternal immune activation (MIA) can be experimentally induced by prenatal administration of polyinosinic:polycytidylic acid (poly I:C), a synthetic viral-like double-stranded RNA. Although this MIA model is adopted in many studies, social and communicative deficits, included in the first diagnostic criterion of ASD, are poorly described in the offspring of poly(I:C)-exposed dams. This study aimed to characterize the impact of prenatal poly(I:C) exposure on socio-communicative behaviors in adolescent rats. For this purpose, social play behavior was assessed in both males and females. We also analyzed quantitative and structural changes in ultrasonic vocalizations (USVs) emitted by rats during the play test. Deficits of social play behaviors were evident only in male rats. Males also emitted a significantly decreased number of USVs during social encounters. Prenatal poly(I:C) exposure also affected acoustic call parameters, as reflected by the increased peak frequencies. Additionally, repetitive behaviors were demonstrated in autistic-like animals regardless of sex. This study demonstrates that prenatal poly(I:C) exposure impairs socio-communicative functioning in adolescent rats. USVs may be a useful tool for identifying early autistic-like abnormalities.

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