Jagoda Stanislawa Jeczmien-Lazur

Bio: Jagoda Stanislawa Jeczmien-Lazur is an academic researcher from Jagiellonian University. The author has contributed to research in topics: Circadian rhythm & Circadian clock. The author has an hindex of 5, co-authored 16 publications receiving 70 citations.

Gamma and infra-slow oscillations shape neuronal firing in the rat subcortical visual system.

Abstract: Key points Neuronal oscillations observed in sensory systems are physiological carriers of information about stimulus features. Rhythm in the infra-slow range, originating from the retina, was previously found in the firing of subcortical visual system nuclei involved in both image and non-image forming functions. The present study shows that the firing of neurons in the lateral geniculate nucleus is also governed by gamma oscillation (∼35 Hz) time-locked to high phase of infra-slow rhythm that codes the intensity of transient light stimulation. We show that both physiological rhythms are synchronized within and between ipsilateral nuclei of the subcortical visual system and are dependent on retinal activity. The present study shows that neurophysiological oscillations characterized by various frequencies not only coexist in the subcortical visual system, but also are subjected to complex interference and synchronization processes. Abstract The physiological function of rhythmic firing in the neuronal networks of sensory systems has been linked with information coding. Also, neuronal oscillations in different frequency bands often change as a signature of brain state or sensory processing. Infra-slow oscillation (ISO) in the neuronal firing dependent on the retinal network has been described previously in the structures of the subcortical visual system. In the present study, we show for the first time that firing of ISO neurons in the lateral geniculate nucleus is also characterized by a harmonic discharge pattern (i.e. action potentials are separated by the intervals governed by fundamental frequency in the gamma range: ∼35 Hz). A similar phenomenon was recently described in the suprachiasmatic nuclei of the hypothalamus: the master biological clock. We found that both gamma and ISO rhythms were synchronized within and between ipsilateral nuclei of the subcortical visual system and were dependent on the retinal activity of the contralateral eye. These oscillatory patterns were differentially influenced by transient and prolonged light stimulation with respect to both frequency change direction and sustainability. The results of the present study show that the firing pattern of neurons in the subcortical visual system is shaped by oscillations from infra-slow and gamma frequency bands that are plausibly generated by the retinal network. Additionally, the results demonstrate that both rhythms are not a distinctive feature of image or non-image forming visual systems but, instead, they comprise two channels carrying distinctive properties of photic information.

Circadian actions of orexins on the retinorecipient lateral geniculate complex in rat

Abstract: Key points Rhythmic processes in living organisms are controlled by biological clocks. The orexinergic system of the lateral hypothalamus carries circadian information to provide arousal for the brain during the active phase. Here, we show that orexins exert an excitatory action in three parts of the lateral geniculate nucleus (LGN), in particular upon directly retinorecipient neurons in the non-image forming visual structures. We provide evidence for the high nocturnal levels of orexins with stable circadian expression of predominant orexin receptor 2 in the LGN. Our data additionally establish the convergence of orexinergic and pituitary adenylate cyclase (PAC)-activating peptide/PAC1 receptor systems (used by melanopsin-expressing retinal ganglion cells), which directly regulates responses to the retinal input. These results help us better understand circadian orexinergic control over the non-image forming subcortical visual system, forming the animal's preparedness for the behaviourally active night. Abstract The orexinergic system of the lateral hypothalamus is tightly interlinked with the master circadian clock and displays daily variation in activity to provide arousal-related excitation for the plethora of brain structures in a circadian manner. Here, using a combination of electrophysiological, optogenetic, histological, molecular and neuronal tracing methods, we explore a particular link between orexinergic and visual systems in rat. The results of the present study demonstrate that orexinergic fibre density at the area of subcortical visual system exerts a clear day to night variability, reaching a maximum at behaviourally active night. We also show pronounced electrophysiological activations of neurons in the lateral geniculate nucleus by orexin A through 24 h, via identified distinct orexin receptors, with the ventrolateral geniculate displaying a daily cycle of responsiveness. In addition, for the first time, we provide a direct evidence for orexins to act on retinorecipient neurons with a high convergence of orexinergic and putatively retinal pituitary adenylate cyclase (PAC)-activating peptide/PAC1 receptor systems. Altogether, the present study ties orexins to non-image forming visual structures with implications for circadian orexinergic modulation of neurons, which process information on ambient light levels.

Rhythmic neuronal activities of the rat nucleus of the solitary tract are impaired by high-fat diet - implications for daily control of satiety.

Abstract: Temporal partitioning of daily food intake is crucial for survival and involves the integration of internal circadian states and external influences such as the light-dark cycle and dietary composition. These intrinsic and extrinsic factors are interdependent with misalignment of circadian rhythms promoting body weight gain, while consumption of a calorie-dense diet elevates the risk of obesity and blunts circadian rhythms. Recently, we defined the circadian properties of the dorsal vagal complex of the brainstem, a structure implicated in the control of food intake and autonomic tone, but whether and how 24 h rhythms in this area are influenced by diet remains unresolved. Here we focused on a key structure of this complex, the nucleus of the solitary tract (NTS). We used a combination of immunohistochemical and electrophysiological approaches together with daily monitoring of body weight and food intake to interrogate how the neuronal rhythms of the NTS are affected by a high-fat diet. We report that short-term consumption of a high-fat diet increases food intake during the day and blunts NTS daily rhythms in neuronal discharge. Additionally, we found that a high-fat diet dampens NTS responsiveness to metabolic neuropeptides, and decreases orexin immunoreactive fibres in this structure. These alterations occur without prominent body weight gain, suggesting that a high-fat diet acts initially to reduce activity in the NTS to disinhibit mechanisms that suppress daytime feeding. KEY POINTS: The dorsal vagal complex of the rodent hindbrain possesses intrinsic circadian timekeeping mechanisms In particular, the nucleus of the solitary tract (NTS) is a robust circadian oscillator, independent of the master suprachiasmatic clock Here, we reveal that rat NTS neurons display timed daily rhythms in their neuronal activity and responsiveness to ingestive cues These daily rhythms are blunted or eliminated by a short-term high-fat diet, together with increased consumption of calories during the behaviourally quiescent day Our results help us better understand the circadian control of satiety by the brainstem and its malfunctioning under a high-fat diet.

Melanopsin expressing intrinsically photosensitive Retinal Ganglion cells in retinal disease

Abstract: Melanopsin containing intrinsically photosensitive Retinal Ganglion Cells (ipRGCs) are a class of photoreceptors with established roles in non-image forming processes. Their contributions to image forming vision may include the estimation of brightness. Animal models have been central for understanding the physiological mechanisms of ipRGC function and there is evidence of conservation of function across species. ipRGCs can be divided into 5 ganglion cell subtypes that show morphological and functional diversity. Research in humans has established that ipRGCs signal environmental irradiance to entrain the central body clock to the solar day for regulating circadian processes and sleep. In addition, ipRGCs mediate the pupil light reflex (PLR), making the PLR a readily accessible behavioural marker of ipRGC activity. Less is known about ipRGC function in retinal and optic nerve disease, with emerging research providing insight into their function in diabetes, retinitis pigmentosa, glaucoma and hereditary optic neuropathy. We briefly review the anatomical distributions, projections and basic physiological mechanisms of ipRGCs, their proposed and known functions in animals and humans with and without eye disease. We introduce a paradigm for differentiating inner and outer retinal inputs to the pupillary control pathway in retinal disease and apply this paradigm to patients with age-related macular degeneration (AMD). In these cases of patients with AMD, we provide the initial evidence that ipRGC function is altered, and that the dysfunction is more pronounced in advanced disease. Our perspective is that with refined pupillometry paradigms, the pupil light reflex can be extended to AMD assessment as a tool for the measurement of inner and outer retinal dysfunction.

The role of chronobiology in drug-resistance epilepsy: The potential use of a variability and chronotherapy-based individualized platform for improving the response to anti-seizure drugs.

Abstract: Despite progress in the development of anti-seizure drugs, drug-resistant epilepsy (DRE) occurs in a third of patients. DRE is associated with poor quality of life and increased risk of sudden, unexplained death. The autonomic nervous system and chronobiology play a role in DRE. In the present paper, we provide a narrative review the mechanisms that underlie DRE and characterize some of the autonomic- and chronotherapy-associated parameters that contribute to the degree of response to therapy. Variability describes the functions of many biological systems, which are dynamic and continuously change over time. These systems are required for responses to continuing internal and external triggers, in order to maintain homeostasis and normal function. Both intra- and inter-subject variability in biological systems have been described. We present a platform, which comprises a personalized-based machine learning closed loop algorithm built on epilepsy-related signatures, autonomic signals, and chronotherapy, as a means for overcoming DRE, improving the response, and reducing the toxicity of current therapies.

Intrinsically photosensitive retinal ganglion cell function,sleep efficiency and depression in advanced age-related macular degeneration

Abstract: Purpose Melanopsin expressing intrinsically photosensitive Retinal Ganglion Cells ( ipRGC ) input to multiple brain regions including those for pupil control, circadian rhythms, sleep and mood regulation. Here we measured ipRGC function and its relationship to sleep quality and depression in patients with advanced age-related macular degeneration ( AMD ). Methods The melanopsin mediated post-illumination pupil response ( PIPR ) was measured in 53 patients with advanced AMD (age 78.8 ± 8.8 years) and in 20 healthy controls (age 72.5 ± 3.3 years). Sleep quality and efficiency was assessed using the Pittsburgh Sleep Quality Index ( PSQI ). Risk of depression was determined using the Centre for Epidemiologic Studies Depression ( CES-D ) questionnaire. Results The AMD group showed significantly reduced pupil constrictions (p = 0.039), PIPR amplitudes (p = 0.003), global sleep scores (p = 0.01) and higher levels of depression (p < 0.001) than the control group. There was a significant correlation between the PIPR amplitude and global sleep score in the AMD group (p = 0.01). The PIPR amplitude significantly correlated with sleep efficiency (p = 0.008; regression; p = 0.01, R2 = 0.13), but not sleep quality (p = 0.23) in the AMD group. There was no correlation between the PIPR and depression scores. Conclusions IpRGC dysfunction in advanced AMD contributes to the observed reduction in sleep efficiency. The correlation between the melanopsin mediated PIPR and sleep may indicate reduced photic input to the suprachiasmatic nucleus ( SCN ) and ventrolateral preoptic ( VLPO ) area due to ipRGC dysfunction in AMD.

Genome-wide meta-analysis of insomnia prioritizes genes associated with metabolic and psychiatric pathways

Abstract: Insomnia is a heritable, highly prevalent sleep disorder for which no sufficient treatment currently exists. Previous genome-wide association studies with up to 1.3 million subjects identified over 200 associated loci. This extreme polygenicity suggested that many more loci remain to be discovered. The current study almost doubled the sample size to 593,724 cases and 1,771,286 controls, thereby increasing statistical power, and identified 554 risk loci (including 364 novel loci). To capitalize on this large number of loci, we propose a novel strategy to prioritize genes using external biological resources and functional interactions between genes across risk loci. Of all 3,898 genes naively implicated from the risk loci, we prioritize 289 and find brain-tissue expression specificity and enrichment in specific gene sets of synaptic signaling functions and neuronal differentiation. We show that this novel gene prioritization strategy yields specific hypotheses on underlying mechanisms of insomnia that would have been missed by traditional approaches.