Ivana Bussi - Academia.edu (original) (raw)
Papers by Ivana Bussi
Proceedings of the National Academy of Sciences of the United States of America, Mar 19, 2024
Nocturnal aversive stimuli presented to mice during eating and drinking outside of their safe nes... more Nocturnal aversive stimuli presented to mice during eating and drinking outside of their safe nest can entrain circadian behaviors, leading to a shift toward daytime activity. We show that the canonical molecular circadian clock is necessary for fear entrainment and that an intact molecular clockwork in the suprachiasmatic nucleus (SCN), the site of the central circadian pacemaker, is necessary but not sufficient to sustain fear entrainment of circadian rhythms. Our results demonstrate that entrainment of a circadian clock by cyclic fearful stimuli can lead to severely mistimed circadian behavior that persists even after the aversive stimulus is removed. Together, our results support the interpretation that circadian and sleep symptoms associated with fear and anxiety disorders may represent the output of a fear-entrained clock.One-Sentence SummaryCyclic fearful stimuli can entrain circadian rhythms in mice, and the molecular clock within the central circadian pacemaker is necessary...
Research Square (Research Square), Mar 17, 2023
There is growing interest in developing artificial lighting that stimulates intrinsically photose... more There is growing interest in developing artificial lighting that stimulates intrinsically photosensitive retinal ganglion cells (ipRGCs) to entrain circadian rhythms to improve mood, sleep, and health. Efforts have focused on stimulating the intrinsic photopigment, melanopsin; however, recently, specialized color vision circuits have been elucidated in the primate retina that transmit blue-yellow cone-opponent signals to ipRGCs. We designed a light that stimulates color-opponent inputs to ipRGCs by temporally alternating short and longer wavelength components that strongly modulate short-wavelength sensitive (S) cones. Two-hour exposure to this Scone modulating light produced an average circadian phase advance of one hour and twenty minutes in 6 subjects (mean age = 30 years) compared to no phase advance for the subjects after exposure to a 500-lux white light equated for melanopsin effectiveness. These results are promising for developing artificial lighting that is highly effective in controlling circadian rhythms by invisibly modulating cone-opponent circuits.
International Journal of Comparative Psychology
Interval timing is a complex cognitive process that involves the estimation of time within the se... more Interval timing is a complex cognitive process that involves the estimation of time within the seconds-to-minutes range. This temporal processing depends on cortico-striatal interactions, as well as an optimal dopaminergic function. On the other hand, the circadian system controls physiological and behavioral functions with periods close to 24 hr. We have previously reported that short-time perception in mice is influenced by the circadian pacemaker, with dopamine signaling as a link between both temporal systems. In this work we evaluated the involvement of melatonin in the circadian modulation of interval timing, as well as the interaction between this hormone and dopamine levels in the striatum. We report that melatonin-depleted rats, by pinealectomy, present an impairment in their ability to estimate a short (24 s) target duration in the peak-interval procedure. Moreover, melatonin administration in drinking water restores interval timing precision in pinealectomized rats. We al...
SSRN Electronic Journal, 2022
Timing and Time Perception: Procedures, Measures, & Applications, 2018
This is an open access chapter distributed under the terms of the prevailing cc-by-nc License.
Behavioural Brain Research
Journal of Pineal Research
Sleep
Study Objectives Sleep disturbances are common co-morbidities of epileptic disorders. Dravet synd... more Study Objectives Sleep disturbances are common co-morbidities of epileptic disorders. Dravet syndrome (DS) is an intractable epilepsy accompanied by disturbed sleep. While there is evidence that daily sleep timing is disrupted in DS, the difficulty of chronically recording polysomnographic sleep from patients has left our understanding of the effect of DS on circadian sleep regulation incomplete. We aim to characterize circadian sleep regulation in a mouse model of DS. Methods Here we exploit long-term electrocorticographic recordings of sleep in a mouse model of DS in which one copy of the Scn1a gene is deleted. This model both genocopies and phenocopies the disease in humans. We test the hypothesis that the deletion of Scn1a in DS mice is associated with impaired circadian regulation of sleep. Results We find that DS mice show impairments in circadian sleep regulation including a fragmented rhythm of NREM sleep and an elongated circadian period of sleep. Next, we characterize re-e...
Current Biology
Highlights d Kiss1 ARH neurons are necessary for the circadian alignment of feeding in mice d Tox... more Highlights d Kiss1 ARH neurons are necessary for the circadian alignment of feeding in mice d Toxin-induced silencing of Kiss1 ARH neurons disrupts circadian rhythms d Activity and sleep patterns are disrupted in the absence of Kiss1 ARH signaling d Kiss1 ARH neurons are a component of circadian thermoregulation
Chronobiology international, Jan 31, 2018
Diurnal subjective sleepiness has been associated with a large number of negative outcomes, such ... more Diurnal subjective sleepiness has been associated with a large number of negative outcomes, such as increased risk of accidents and development of mental disorders as depression and anxiety. However, the role of the diurnal subjective sleepiness as a mediator is poorly understood. The goal of the present study was to examine the role of diurnal subjective sleepiness as a mediator of the relationship between sex, chronotype and anxiety symptoms in healthy young adults. Four-hundred and sixty-seven healthy young adults (64.8% females, age range 18-32 years, mean 20.7, ±2.3) were evaluated with validated and widely used scales for the measurement of diurnal sleepiness, anxiety symptoms and morningness-eveningness preference. We have found that diurnal subjective sleepiness correlated with anxiety symptoms when evaluated both in the total sample and within chronotypes. This association was more important in females than in males (p < 0.0001). Regarding chronotype, only for morning-ty...
Mechanisms of Circadian Systems in Animals and Their Clinical Relevance, 2014
Philosophical Transactions of the Royal Society B: Biological Sciences, 2014
Biological clocks are genetically encoded oscillators that allow organisms to keep track of their... more Biological clocks are genetically encoded oscillators that allow organisms to keep track of their environment. Among them, the circadian system is a highly conserved timing structure that regulates several physiological, metabolic and behavioural functions with periods close to 24 h. Time is also crucial for everyday activities that involve conscious time estimation. Timing behaviour in the second-to-minutes range, known as interval timing, involves the interaction of cortico-striatal circuits. In this review, we summarize current findings on the neurobiological basis of the circadian system, both at the genetic and behavioural level, and also focus on its interactions with interval timing and seasonal rhythms, in order to construct a multi-level biological clock.
Brain Research, 2011
Temporal perception is fundamental to environmental adaptation in humans and other animals. To de... more Temporal perception is fundamental to environmental adaptation in humans and other animals. To deal with timing and time perception, organisms have developed multiple systems that are active over a broad range of order of magnitude, the most important being circadian timing, interval timing and millisecond timing. The circadian pacemaker is located in the suprachiasmatic nuclei (SCN) of the hypothalamus, and is driven by a selfsustaining oscillator with a period close to 24 h. Time estimation in the second-to-minutes rangeknown as interval timinginvolves the interaction of the basal ganglia and the prefrontal cortex. In this work we tested the hypothesis that interval timing in mice is sensitive to circadian modulations. Animals were trained following the peak-interval (PI) procedure. Results show significant differences in the estimation of 24-second intervals at different times of day, with a higher accuracy in the group trained at night, which were maintained under constant dark (DD) conditions. Interval timing was also studied in animals under constant light (LL) conditions, which abolish circadian rhythmicity. Mice under LL conditions were unable to acquire temporal control in the peak interval procedure. Moreover, short time estimation in animals subjected to circadian desynchronizations (modeling jet lag-like situations) was also affected. Taken together, our results indicate that short-time estimation is modulated by the circadian clock.
European Journal of Neuroscience, 2014
Duration discrimination within the seconds-to-minutes range, known as interval timing, involves t... more Duration discrimination within the seconds-to-minutes range, known as interval timing, involves the interaction of cortico-striatal circuits via dopaminergic-glutamatergic pathways. Besides interval timing, most (if not all) organisms exhibit circadian rhythms in physiological, metabolic and behavioral functions with periods close to 24 h. We have previously reported that both circadian disruption and desynchronization impaired interval timing in mice. In this work we studied the involvement of dopamine (DA) signaling in the interaction between circadian and interval timing. We report that daily injections of levodopa improved timing performance in the peak-interval procedure in C57BL/6 mice with circadian disruptions, suggesting that a daily increase of DA is necessary for an accurate performance in the timing task. Moreover, striatal DA levels measured by reverse-phase high-pressure liquid chromatography indicated a daily rhythm under light/dark conditions. This daily variation was affected by inducing circadian disruption under constant light (LL). We also demonstrated a daily oscillation in tyrosine hydroxylase levels, DA turnover (3,4-dihydroxyphenylacetic acid/DA levels), and both mRNA and protein levels of the circadian component Period2 (Per2) in the striatum and substantia nigra, two brain areas relevant for interval timing. None of these oscillations persisted under LL conditions. We suggest that the lack of DA rhythmicity in the striatum under LL - probably regulated by Per2 - could be responsible for impaired performance in the timing task. Our findings add further support to the notion that circadian and interval timing share some common processes, interacting at the level of the dopaminergic system.
Proceedings of the National Academy of Sciences of the United States of America, Mar 19, 2024
Nocturnal aversive stimuli presented to mice during eating and drinking outside of their safe nes... more Nocturnal aversive stimuli presented to mice during eating and drinking outside of their safe nest can entrain circadian behaviors, leading to a shift toward daytime activity. We show that the canonical molecular circadian clock is necessary for fear entrainment and that an intact molecular clockwork in the suprachiasmatic nucleus (SCN), the site of the central circadian pacemaker, is necessary but not sufficient to sustain fear entrainment of circadian rhythms. Our results demonstrate that entrainment of a circadian clock by cyclic fearful stimuli can lead to severely mistimed circadian behavior that persists even after the aversive stimulus is removed. Together, our results support the interpretation that circadian and sleep symptoms associated with fear and anxiety disorders may represent the output of a fear-entrained clock.One-Sentence SummaryCyclic fearful stimuli can entrain circadian rhythms in mice, and the molecular clock within the central circadian pacemaker is necessary...
Research Square (Research Square), Mar 17, 2023
There is growing interest in developing artificial lighting that stimulates intrinsically photose... more There is growing interest in developing artificial lighting that stimulates intrinsically photosensitive retinal ganglion cells (ipRGCs) to entrain circadian rhythms to improve mood, sleep, and health. Efforts have focused on stimulating the intrinsic photopigment, melanopsin; however, recently, specialized color vision circuits have been elucidated in the primate retina that transmit blue-yellow cone-opponent signals to ipRGCs. We designed a light that stimulates color-opponent inputs to ipRGCs by temporally alternating short and longer wavelength components that strongly modulate short-wavelength sensitive (S) cones. Two-hour exposure to this Scone modulating light produced an average circadian phase advance of one hour and twenty minutes in 6 subjects (mean age = 30 years) compared to no phase advance for the subjects after exposure to a 500-lux white light equated for melanopsin effectiveness. These results are promising for developing artificial lighting that is highly effective in controlling circadian rhythms by invisibly modulating cone-opponent circuits.
International Journal of Comparative Psychology
Interval timing is a complex cognitive process that involves the estimation of time within the se... more Interval timing is a complex cognitive process that involves the estimation of time within the seconds-to-minutes range. This temporal processing depends on cortico-striatal interactions, as well as an optimal dopaminergic function. On the other hand, the circadian system controls physiological and behavioral functions with periods close to 24 hr. We have previously reported that short-time perception in mice is influenced by the circadian pacemaker, with dopamine signaling as a link between both temporal systems. In this work we evaluated the involvement of melatonin in the circadian modulation of interval timing, as well as the interaction between this hormone and dopamine levels in the striatum. We report that melatonin-depleted rats, by pinealectomy, present an impairment in their ability to estimate a short (24 s) target duration in the peak-interval procedure. Moreover, melatonin administration in drinking water restores interval timing precision in pinealectomized rats. We al...
SSRN Electronic Journal, 2022
Timing and Time Perception: Procedures, Measures, & Applications, 2018
This is an open access chapter distributed under the terms of the prevailing cc-by-nc License.
Behavioural Brain Research
Journal of Pineal Research
Sleep
Study Objectives Sleep disturbances are common co-morbidities of epileptic disorders. Dravet synd... more Study Objectives Sleep disturbances are common co-morbidities of epileptic disorders. Dravet syndrome (DS) is an intractable epilepsy accompanied by disturbed sleep. While there is evidence that daily sleep timing is disrupted in DS, the difficulty of chronically recording polysomnographic sleep from patients has left our understanding of the effect of DS on circadian sleep regulation incomplete. We aim to characterize circadian sleep regulation in a mouse model of DS. Methods Here we exploit long-term electrocorticographic recordings of sleep in a mouse model of DS in which one copy of the Scn1a gene is deleted. This model both genocopies and phenocopies the disease in humans. We test the hypothesis that the deletion of Scn1a in DS mice is associated with impaired circadian regulation of sleep. Results We find that DS mice show impairments in circadian sleep regulation including a fragmented rhythm of NREM sleep and an elongated circadian period of sleep. Next, we characterize re-e...
Current Biology
Highlights d Kiss1 ARH neurons are necessary for the circadian alignment of feeding in mice d Tox... more Highlights d Kiss1 ARH neurons are necessary for the circadian alignment of feeding in mice d Toxin-induced silencing of Kiss1 ARH neurons disrupts circadian rhythms d Activity and sleep patterns are disrupted in the absence of Kiss1 ARH signaling d Kiss1 ARH neurons are a component of circadian thermoregulation
Chronobiology international, Jan 31, 2018
Diurnal subjective sleepiness has been associated with a large number of negative outcomes, such ... more Diurnal subjective sleepiness has been associated with a large number of negative outcomes, such as increased risk of accidents and development of mental disorders as depression and anxiety. However, the role of the diurnal subjective sleepiness as a mediator is poorly understood. The goal of the present study was to examine the role of diurnal subjective sleepiness as a mediator of the relationship between sex, chronotype and anxiety symptoms in healthy young adults. Four-hundred and sixty-seven healthy young adults (64.8% females, age range 18-32 years, mean 20.7, ±2.3) were evaluated with validated and widely used scales for the measurement of diurnal sleepiness, anxiety symptoms and morningness-eveningness preference. We have found that diurnal subjective sleepiness correlated with anxiety symptoms when evaluated both in the total sample and within chronotypes. This association was more important in females than in males (p < 0.0001). Regarding chronotype, only for morning-ty...
Mechanisms of Circadian Systems in Animals and Their Clinical Relevance, 2014
Philosophical Transactions of the Royal Society B: Biological Sciences, 2014
Biological clocks are genetically encoded oscillators that allow organisms to keep track of their... more Biological clocks are genetically encoded oscillators that allow organisms to keep track of their environment. Among them, the circadian system is a highly conserved timing structure that regulates several physiological, metabolic and behavioural functions with periods close to 24 h. Time is also crucial for everyday activities that involve conscious time estimation. Timing behaviour in the second-to-minutes range, known as interval timing, involves the interaction of cortico-striatal circuits. In this review, we summarize current findings on the neurobiological basis of the circadian system, both at the genetic and behavioural level, and also focus on its interactions with interval timing and seasonal rhythms, in order to construct a multi-level biological clock.
Brain Research, 2011
Temporal perception is fundamental to environmental adaptation in humans and other animals. To de... more Temporal perception is fundamental to environmental adaptation in humans and other animals. To deal with timing and time perception, organisms have developed multiple systems that are active over a broad range of order of magnitude, the most important being circadian timing, interval timing and millisecond timing. The circadian pacemaker is located in the suprachiasmatic nuclei (SCN) of the hypothalamus, and is driven by a selfsustaining oscillator with a period close to 24 h. Time estimation in the second-to-minutes rangeknown as interval timinginvolves the interaction of the basal ganglia and the prefrontal cortex. In this work we tested the hypothesis that interval timing in mice is sensitive to circadian modulations. Animals were trained following the peak-interval (PI) procedure. Results show significant differences in the estimation of 24-second intervals at different times of day, with a higher accuracy in the group trained at night, which were maintained under constant dark (DD) conditions. Interval timing was also studied in animals under constant light (LL) conditions, which abolish circadian rhythmicity. Mice under LL conditions were unable to acquire temporal control in the peak interval procedure. Moreover, short time estimation in animals subjected to circadian desynchronizations (modeling jet lag-like situations) was also affected. Taken together, our results indicate that short-time estimation is modulated by the circadian clock.
European Journal of Neuroscience, 2014
Duration discrimination within the seconds-to-minutes range, known as interval timing, involves t... more Duration discrimination within the seconds-to-minutes range, known as interval timing, involves the interaction of cortico-striatal circuits via dopaminergic-glutamatergic pathways. Besides interval timing, most (if not all) organisms exhibit circadian rhythms in physiological, metabolic and behavioral functions with periods close to 24 h. We have previously reported that both circadian disruption and desynchronization impaired interval timing in mice. In this work we studied the involvement of dopamine (DA) signaling in the interaction between circadian and interval timing. We report that daily injections of levodopa improved timing performance in the peak-interval procedure in C57BL/6 mice with circadian disruptions, suggesting that a daily increase of DA is necessary for an accurate performance in the timing task. Moreover, striatal DA levels measured by reverse-phase high-pressure liquid chromatography indicated a daily rhythm under light/dark conditions. This daily variation was affected by inducing circadian disruption under constant light (LL). We also demonstrated a daily oscillation in tyrosine hydroxylase levels, DA turnover (3,4-dihydroxyphenylacetic acid/DA levels), and both mRNA and protein levels of the circadian component Period2 (Per2) in the striatum and substantia nigra, two brain areas relevant for interval timing. None of these oscillations persisted under LL conditions. We suggest that the lack of DA rhythmicity in the striatum under LL - probably regulated by Per2 - could be responsible for impaired performance in the timing task. Our findings add further support to the notion that circadian and interval timing share some common processes, interacting at the level of the dopaminergic system.