Slow Oscillations in the Mouse Hippocampus Entrained by Nasal Respiration

Different types of network oscillations occur in different behavioral, cognitive, or vigilance states. The rodent hippocampus expresses prominentoscillations atfrequencies between 4 and 12Hz,which are superimposed by phase-coupledoscillations (30 –100Hz).These patterns entrain multineuronal activity over large distances and have been implicated in sensory information processing and memory formation. Here we report a new type of oscillation at near- frequencies (2– 4 Hz) in the hippocampus of urethane-anesthetized mice. The rhythm is highly coherent with nasal respiration and with rhythmic field potentials in the olfactory bulb: hence, we called it hippocampal respiration-induced oscillations. Despite the similarity in frequency range, several features distinguish this pattern from locally generatedoscillations: hippocampal respiration-induced oscillations have a unique laminar amplitude profile, are resistant to atropine, couple differentlytooscillations, and are abolished when nasal airflow is bypassed bytracheotomy. Hippocampal neurons are entrained by both the respiration-induced rhythm and concurrent oscillations, suggesting a direct interaction between endogenous activity in the hippocampus and nasal respiratory inputs. Our results demonstrate that nasal respiration strongly modulates hippocampal network activity in mice, providing a long-range synchronizing signal between olfactory and hippocampal networks.

Versão breve da social rhythm metric: um instrumento para avaliar ritmo social de pacientes com acidente vascular cerebral

Stroke is a neurological disorder caused by restriction of blood flow to the brain, which generates directly a deficit of functionality that affects the quality of life of patients. The aim of this study was to establish a short version of the Social Rhythm Scale (SRM), to assess the social rhythm of stroke patients. The sample consisted of 84 patients, of both sexes, with injury time exceeding 6 months. For seven days, patients recorded the time held 17 activities of SRM. Data analysis was performed using a principal components factor analysis with varimax rotation of the full version of SRM in order to determine which activities could compose brief versions of SRM. We then carried out a comparison of hits, the ALI (Level Activity Index) and SRM, between versions, by Kruskal-Walls and the Mann-Whitney test. The Spearman correlation test was used to evaluate the correlation between the score of the full version of SRM with short versions. It was found that the activities of SRM were distributed in three versions: the first and second with 6 activities and third with 3 activities. Regarding hits, it was found that they ranged from 4.9 to 5.8 on the first version; 2.3 to 3.8 in version 2 and 2.8 to 6.2 in version 3, the first the only version that did not show low values. The analysis of ALI, in version 1, the median was 29, in version 2 was 14 and in version 3 was 18. Significant difference in the values of ALI between versions 1 and 2, between 2 and 3 and between versions 1 and 3. The highest median was found in the first version, formed by activities: out of bed, first contact, drink coffee, watch TV in the evening and go to bed. The lowest median was observed in the second version and this was not what had fewer activities, but which had social activities. The medians of the SRM version 1 was 6, version 2 was 4 and version 3 was 6. Significant difference in the values of SRM between versions 1 and 2 and between 2 and 3, but no significant difference between versions 1 and 3. Through analysis, we found a significant correlation only between the full version and the version 1 (R2 = 0.61) (p <0.05), no correlation was found with version 2 (R2 = 0.007) nor with version 3 (R2 = 0.002), this was finally a factor to consider version 1 as the short brazilian version of the Social Rhythm Metric for stroke patients

Avaliação comportamental e neuroquímica de ratos em dessincronização forçada: possíveis implicações para um modelo animal de oscilações no humor

Bipolar disorder has been growing in several countries. It is a disease with high mortality and has been responsible by the social isolation of the patients. Bipolar patients have alterations in circadian timing system, showing a phase shift in various physiological variables. There are several arguments demonstrating alterations in circadian rhythms may be part of the bipolar disorder pathophysiology. Given the necessity for further elucidation, the goal of this study was to validate the forced desynchronization protocol as an animal model for bipolar disorder. To do this, Wistar rats were submitted to a forced desynchronization protocol which consists in a symmetrical light dark cycle with 22h. Under this protocol, rats dissociate the locomotor activity rhythm into two components: one synchronized to the light / dark cycle with 22h, and another component with period longer than 24 hours following the animal endogenous period. These rhythms with different periods sometimes there is coincidence, which we named CAP (Coincidence Active Phase) and the opposite phase, non-coincidence, called NCAP (Non-Concidence Active Phase). The hypothesis is that in CAP animals present a mania-like behavior and animals in NCAP depressive-like behavior. We found some evidence described in detail throughout this thesis. In sum, the animals under forced desynchronization protocol were more stressed, showed an increase in stereotypic behaviors such as grooming and reduction in other behaviors such as risk assessment and vertical exploration when compared to the control group. The CAP animals showed increased locomotor activity, especially during the dark phase when compared to controls (rats under T24) and less depressive behavior in the forced swim test. The animals in NCAP showed a higher anxiety in elevated plus maze, but they don t have ahnedonia. The animals under dissociation have more labeled 5HT1A cells at the amygdala area, which appoint that they have more amygdala inhibition. Taking these data together, we could partially validated the forced desynchronization protocol as an animal model for mood oscillations

Efeitos de vocalizações de co-específicos e do escuro sobre o ritmo circadiano da atividade motora em sagüis (Callithrix jacchus)

The principal zeitgeber for most of species is the light-dark photocycle (LD), though other environment factors as food availability, temperature and social cues may act. Daily adjustment of the circadian pacemaker may result from integration of environmental photic and non-photic cues with homeostatic cues. Characterization of non-photic effects on circadian timing system in diurnal mammals is scarce in relation to nocturnal, especially for ecologically significant cues. Thus, we analyzed the effect of conspecific vocalizations and darkness on circadian activity rhythm (CAR) in the diurnal primate Callithirx jacchus. With this objective 7 male adults were isolated in a room with controlled illumination, temperature (26,8 ± 0,2°C) and humidity (81,6 ± 3,6%), and partial acoustic isolation. Initially they were under LD 12:12 (~300:2 lux), and subsequently under constant illumination (~2 lux). Two pulses of conspecific vocalizations were applied in total darkness, separated by 22 days, at 7:30 h (external time) during 1 h. They induced phase delays at circadian times (CTs) 1 and 10 and predominantly phase advances at CTs 9 and 15. After that, two dark pulses were applied, separated by 14 days, during 1 h at 7:30 h (external time). These pulses induced phase delays at CTs 2, 3 and 18, predominantly phase advances at CTs 8, 10 and 19, and no change at CT 14. However, marmosets CAR showed oscillations in endogenous period and active phase duration influenced by vocalizations from animals outside the experimental room, which interfered on the phase responses to pulses. Furthermore, social masking and relative coordination with colony were observed. Therefore, phase responses obtained in this work cannot be attributed only to pulses. Afterwards, pulses of conspecific vocalizations were applied in total darkness at 19:00 h (external time), during 1 h for 5 consecutive days, and after 21 days, for 30 consecutive days, on attempt to synchronize the CAR. No animal was synchronized by these daily pulses, although oscillations in endogenous period were observed for all. This result may be due to habituation. Other possibility is the absence of social significance of the vocalizations for the animals due to random reproduction, since each vocalization has a function that could be lost by a mixture of sounds. In conclusion, conspecific vocalizations induce social masking and relative coordination in marmosets CAR, acting as weak zeitgeber

Caracaterização do núcleo pré-geniculado do sagüi (Callithrix jacchus) :projeção retiniana, neuroquímica e atividade celular (expressão de FOS)

In rodents, the suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL) are the main components of the circadian system. The SCN is considerate the site of an endogenous biological clock because can to generate rhythm and to synchronize to the environmental cues (zeitgebers) and IGL has been related as one of the main areas that modulate the action of SCN. Both receive projections of ganglion cells of retina and this projection to SCN is called retinohypothalamic tract (RHT). Moreover, the IGL is connected with SCN through of geniculohypothalamic tract (GHT). In primates (include humans) was not still demonstrated the presence of a homologous structure to the IGL. It is believed that the pregeniculate nucleus (PGN) can be the answer, but nothing it was still proven. Trying to answer that question, the objective of our study is to do a comparative analysis among PGN and IGL through of techniques immunohystochemicals, neural tracers and FOS expression after dark pulses. For this, we used as experimental model a primate of the new world, the common marmoset (Callithrix jacchus). Ours results may contribute to the elucidation of this lacuna in the circadian system once that the IGL is responsible for the transmission of nonphotic information to SCN and participate in the integration between photic and nonphotic stimulus to adjust the function of the SCN. In this way to find a same structure in primates represent an important achieve in the understanding of the biological rhythms in those animals

Relação entre o ciclo sono e vigília e a função cardiorrespiratória em estudantes de medicina

Students, normally, present an irregular sleep pattern characterized by delays in sleep onset and offset from weekdays to weekends, short sleep duration on weekdays and long sleep duration on weekends. The reduction of the necessary sleep and the irregularity in the sleep patterns provoke relevant short- and long-term impairments on performances, for example, in cardiorespiratory function. The cardiorespiratory performance represents, in addition to fitness, traces associated to health conditions and in several studies to pattern and/or individual s sleep quality. The aim of this study was to evaluate the pattern of the sleep-wake cycle and the cardiorespiratory function of medical students under different class schedules. The study was accomplished with two classes of medical students of UFRN, one had classes at 7 am (n = 47) and the second had classes at 8 am (n = 41) during the week. On the first stage of the study all volunteers filled out an anamnesis, the International Physical Activity questionnaire, the Pittsburgh index of sleep quality, the Portuguese version of the Horne and Östberg cronotype questionnaire, the Health and Sleep questionnaire and the Epworth Scale of Somnolence (ESS). On the second stage, 24 students (12 of each class) had their activity rhythm monitored by actimeters set to record activity at a 2-min interval for 14 days concomitant to the completion of the sleep diary. In this same stage, each volunteer performed the effort test (treadmill) only once in the morning period (between 9:00 and 11:00). The students showed an irregular pattern of the sleep-wake cycle and this irregularity is strongly influenced by the class schedules, in addition to the contribution of the academic demand, social activities and endogenous factors. The students who woke up earlier showed greater irregularity in the sleep-wake pattern. The earlier was the class schedule the worse was the sleep quality and the greater was the frequency of students with excessive diurnal somnolence. The classes schedules and the irregular pattern of the sleep-wake cycle did not show effect on the cardiorespiratory performance of the medical students. The performance on the test seems to be affected by other factors, which can be related to the pattern of the sleep-wake cycle or not. Therefore, it is suggested that the late start of classes provokes less irregularity on the pattern of the sleep-wake cycle. However, it was observed that this irregularity and the class schedule seem not to affect the cardiorespiratory performance directly

Influência da auto seleção à luz no ritmo circadiano de atividade motora em Callithrix Jacchus

Marmosets, Callithrix jacchus, are strictly diurnal animals. The motor activity rhythmicity is generated by the circadian timing system and is modulated by environmental factors, mainly by photic stimuli that compose the light-dark cycle. Photic stimuli can reset the biological oscilators changing activity motor pattern, by a mechanism called entrainment. Otherwise, light can act directly on expressed rhythm, without act on the biological oscillators, promoting the masking. Thus, photic stimuli can synchronize the circadian activity rhythm (CAR) by two distinct mechanisms, acting isolated or at a combined way. Among the elements that can influence photic synchronization, the duration and time of photic exposure is pointed out. If in the natural environment the marmoset can choose places of different intensity illumination and is synchronized to light-dark cycle (LD), how the photic synchronization mechanism can be evaluated in laboratory by light self-selection? With objective to response this question, four adult male marmosets were studied at two conditions: with and without sleeping box. The animals were submitted to a LD cycle (12:12/ 350:2 lx) and constant light (LL: 350 lx) conditions in individual cages with an opaque sleeping box, that permitted the light self-selection. At the room, the temperature was 25.6 ºC (± 0.3 ºC) and humidity was 78.7 (± 5%). The motor activity was recorded at 5 min bins by infrared movement sensors installed at the top of the cages. The motor activity profile was distinct at the two conditions: without the sleeping box protection against light, the activity frequency was higher at CT 11-12 (ANOVA; F(3.23) = 62.27; p < 0.01). Also, the duration of the active phase (α) was prolonged of about 1 h (t test, p < 0.05) and the animals showed a significant delay on the activity onset and offset (t test, p < 0.05) and at the acrophase (confidence intervals of 5%) of CAR. In LL, the light continuous exposure prolonged the active phase and influenced the endogenous expression of the circadian activity rhythm period. From the result analysis, it is concluded that the light self-selection can modify several parameters of CAR in marmosets, allowing the study of the synchronization mechanism using the burrow model. Thus, without sleeping box there was a phase delay between the CAR and LD (entrainment) and an increase of activity near lights off (positive masking). Furthermore, in LL, the light continuous exposure modifies α and the endogenous expression of CAR. It is suggested that the light self-selection might be take into account at investigations that evaluate the biological rhythmicity in marmosets

Mecanismos de sincronia social no ritmo circadiano de atividade durante a coabitação em casais de saguis (Callithrix jacchus)

In marmosets, it was observed that the synchrony among circadian activity profiles of animals that cohabite in family groups is stronger than those of the same sex and age of different families. Inside the group, it is stronger between the younger ones than between them and their parents. However, the mechanisms involved in the social synchrony are unknown. With the aim to investigate the synchronization mechanisms involved in the synchrony between the circadian activity profiles during cohabitation in pairs of marmosets, the motor activity was continuously registered by the use of actmeters on three dyads. The pairs were maintained in two different conditions of illumination: light-dark cycle LD 12:12 (LD cohabitation I – 21 days), and thereafter in LL (~350 lux). Under LL, the pairs were submitted to four experimental situations: 1. Cohabitation (LLJ I – 24 days), 2. Removal of one member of the pair to another room with similar conditions (LLS I – 20 days), 3. Reintroduction of the separated member in the cage of the first situation (LLJ II – 30 days) and 4. Removal of a member from each pair to another experimental room (LLS II – 7 days), to evaluate the mechanisms of synchronization. Ultimately, the members of each pair were reintroduced in the cage and were kept in LD cycle 12:12 (LDJ II – 11 days). The rhythms of pairs free-ran in LL, with identical periods between the members of each pair during the two stages of cohabitation. In the stages in which the animals were separated, only the rhythms of two females free-ran in the first stage and of three animals in the second one. In those conditions, the rhythms of animals of each pair showed different endogenous periods. Besides, during cohabitation in LD and LL, the members of each pair showed a stable phase relationship in the beginning of the active phase, while in the stages in which the animals were separated it was noticed a breaking in the stability in the phase relationships between the circadian activity profiles, with an increase in the difference in the phase angles between them. During cohabitation, at the transition between LD and LL, all animals showed free-running rhythms anticipating progressively the beginning and the end of the active phase in a phase similar to the previous condition, showing signs of entrainment to the previous LD. While in the posterior stages this was observed in only three animals between: LLT I and LLS I, and LLT II and LLS II, evidencing signs of entrainment to social cues between the members of each pair. On the other hand, one animal delayed progressively between LLT I and LLS I, three animals delayed between LLS I and LLT II, and three animals between LLT II and LLS II, perhaps by entrainment to the animals maintained outdoors in the colony. Similar process was observed in four animals between LLS II and LDT II, indicating entrainment to LD. In the transition between LLS I and LLT II, signs of masking was observed in the rhythm of a female in response to the male and in another pair in the rhythm of the male in regard to that of the female. The general and maximum correlations in the circadian activity profiles were stronger during cohabitation in LD and LL than in the absence of social contact in LL, evidencing the social effect. The cohabiting pairs had higher values of the maximum correlation in LD and LL than when the profiles were correlated to animals of different cages, with same or different sexes. Similar results were observed in the general correlation. Therefore, it is suggested that cohabitation induces a strong synchrony between circadian activity profiles in marmosets, which involves entrainment and masking. Nevertheless, additional studies are necessary to evaluate the effect of social cues on the synchronization of the circadian rhythm in pairs of marmosets in the absence of external social cues in order to confirm this hypothesis.

Caracterização do ritmo circadiano de atividade e repouso em saguis idosos (Callithrix Jacchus)

Advanced age may become a limiting factor for the maintenance of rhythms in organisms, reducing the capacity of generation and synchronization of biological rhythms. In this study, the influence of aging on the expression of endogenous periodicity and synchronization (photic and social) of the circadian activity rhythm (CAR) was evaluated in a diurnal primate, the marmoset (Callithrix jacchus). This study had two approaches: one with longitudinal design, performed with a male marmoset in two different phases: adult (three years) and older (9 y.o.) (study 1) and the second, a transversal approach, with 6 old (♂: 9.7 ± 2.0 y.o.) and 11 adults animals (♂: 4.2 ± 0.8 y.o.) (study 2). The evaluation of the photic synchronization involved two conditions in LD (natural and artificial illuminations). In study 1, the animal was subjected to the following stages: LD (12:12 ~ 350: ~ 2 lx), LL (~ 350 lx) and LD resynchronization. In the second study, the animals were initially evaluated in natural LD, and then the same sequence stages of study 1. During the LL stage in study 2, the vocalizations of conspecifics kept in natural LD on the outside of the colony were considered temporal cue to the social synchronization. The record of the activity was performed automatically at intervals of five minutes through infrared sensor and actimeters, in studies 1 and 2, respectively. In general, the aged showed a more fragmented activity pattern (> IV < H and > PSD, ANOVA, p < 0.05), lower levels of activity (ANOVA, p < 0.05) and shorter duration of active phase (ANOVA, p < 0.05) in LD conditions, when compared to adults. In natural LD, the aged presented phase delay pronounced for onset and offset of active phase (ANOVA, p < 0.05), while the adults had the active phase more adjusted to light phase. Under artificial LD, there was phase advance and greater adjustment of onset and offset of activity in relation to the LD in the aged (ANOVA, p < 0.05). In LL, there was a positive correlation between age and the endogenous period () in the first 20 days (Spearman correlation, p < 0.05), with prolonged  held in two aged animals. In this condition, most adults showed free-running period of the circadian activity rhythm with  < 24 h for the first 30 days and later on relative coordination mediated by auditory cues. In study 2, the cross-correlation analysis between the activity profiles of the animals in LL with control animals kept under natural LD, found that there was less social synchronization in the aged. With the resubmission to the LD, the resynchronization rate was slower in the aged (t-test; p < 0.05) and in just one aged animal there was a loss of resynchronization capability. According to the data set, it is suggested that the aging in marmosets may be related to: 1) lower amplitude and greater fragmentation of the activity, accompanied to phase delay with extension of period, caused by changes in a photic input, in the generation and behavioral expression of the CAR; 2) lower capacity of the circadian activity rhythm to photic synchronization, that can become more robust in artificial lighting conditions, possibly due to the higher light intensities at the beginning of the active phase due to the abrupt transitions between the light and dark phases; and 3) smaller capacity of non-photic synchronization for auditory cues from conspecifics, possibly due to reducing sensory inputs and responsiveness of the circadian oscillators to auditory cues, what can make the aged marmoset most vulnerable, as these social cues may act as an important supporting factor for the photic synchronization.

Caracterização do ritmo circadiano de atividade e repouso em saguis idosos (Callithrix Jacchus)

Advanced age may become a limiting factor for the maintenance of rhythms in organisms, reducing the capacity of generation and synchronization of biological rhythms. In this study, the influence of aging on the expression of endogenous periodicity and synchronization (photic and social) of the circadian activity rhythm (CAR) was evaluated in a diurnal primate, the marmoset (Callithrix jacchus). This study had two approaches: one with longitudinal design, performed with a male marmoset in two different phases: adult (three years) and older (9 y.o.) (study 1) and the second, a transversal approach, with 6 old (♂: 9.7 ± 2.0 y.o.) and 11 adults animals (♂: 4.2 ± 0.8 y.o.) (study 2). The evaluation of the photic synchronization involved two conditions in LD (natural and artificial illuminations). In study 1, the animal was subjected to the following stages: LD (12:12 ~ 350: ~ 2 lx), LL (~ 350 lx) and LD resynchronization. In the second study, the animals were initially evaluated in natural LD, and then the same sequence stages of study 1. During the LL stage in study 2, the vocalizations of conspecifics kept in natural LD on the outside of the colony were considered temporal cue to the social synchronization. The record of the activity was performed automatically at intervals of five minutes through infrared sensor and actimeters, in studies 1 and 2, respectively. In general, the aged showed a more fragmented activity pattern (> IV < H and > PSD, ANOVA, p < 0.05), lower levels of activity (ANOVA, p < 0.05) and shorter duration of active phase (ANOVA, p < 0.05) in LD conditions, when compared to adults. In natural LD, the aged presented phase delay pronounced for onset and offset of active phase (ANOVA, p < 0.05), while the adults had the active phase more adjusted to light phase. Under artificial LD, there was phase advance and greater adjustment of onset and offset of activity in relation to the LD in the aged (ANOVA, p < 0.05). In LL, there was a positive correlation between age and the endogenous period () in the first 20 days (Spearman correlation, p < 0.05), with prolonged  held in two aged animals. In this condition, most adults showed free-running period of the circadian activity rhythm with  < 24 h for the first 30 days and later on relative coordination mediated by auditory cues. In study 2, the cross-correlation analysis between the activity profiles of the animals in LL with control animals kept under natural LD, found that there was less social synchronization in the aged. With the resubmission to the LD, the resynchronization rate was slower in the aged (t-test; p < 0.05) and in just one aged animal there was a loss of resynchronization capability. According to the data set, it is suggested that the aging in marmosets may be related to: 1) lower amplitude and greater fragmentation of the activity, accompanied to phase delay with extension of period, caused by changes in a photic input, in the generation and behavioral expression of the CAR; 2) lower capacity of the circadian activity rhythm to photic synchronization, that can become more robust in artificial lighting conditions, possibly due to the higher light intensities at the beginning of the active phase due to the abrupt transitions between the light and dark phases; and 3) smaller capacity of non-photic synchronization for auditory cues from conspecifics, possibly due to reducing sensory inputs and responsiveness of the circadian oscillators to auditory cues, what can make the aged marmoset most vulnerable, as these social cues may act as an important supporting factor for the photic synchronization.

Slow Oscillations in the Mouse Hippocampus Entrained by Nasal Respiration

Different types of network oscillations occur in different behavioral, cognitive, or vigilance states. The rodent hippocampus expresses prominentoscillations atfrequencies between 4 and 12Hz,which are superimposed by phase-coupledoscillations (30 –100Hz).These patterns entrain multineuronal activity over large distances and have been implicated in sensory information processing and memory formation. Here we report a new type of oscillation at near- frequencies (2– 4 Hz) in the hippocampus of urethane-anesthetized mice. The rhythm is highly coherent with nasal respiration and with rhythmic field potentials in the olfactory bulb: hence, we called it hippocampal respiration-induced oscillations. Despite the similarity in frequency range, several features distinguish this pattern from locally generatedoscillations: hippocampal respiration-induced oscillations have a unique laminar amplitude profile, are resistant to atropine, couple differentlytooscillations, and are abolished when nasal airflow is bypassed bytracheotomy. Hippocampal neurons are entrained by both the respiration-induced rhythm and concurrent oscillations, suggesting a direct interaction between endogenous activity in the hippocampus and nasal respiratory inputs. Our results demonstrate that nasal respiration strongly modulates hippocampal network activity in mice, providing a long-range synchronizing signal between olfactory and hippocampal networks.