@article{pmid41429783,

title = {Latent brain subtypes of chronotype reveal unique behavioral and health profiles across population cohorts},

author = {Le Zhou and Karin Saltoun and Justin Marotta and Shambhavi Aggarwal and Jakub Kopal and Julie Carrier and Kai-Florian Storch and Robin I M Dunbar and Danilo Bzdok},

doi = {10.1038/s41467-025-66784-8},

issn = {2041-1723},

year  = {2025},

date = {2025-12-01},

journal = {Nat Commun},

volume = {16},

number = {1},

pages = {11550},

abstract = {Chronotype is shaped by the complex interplay of endogenous and exogenous factors. This time-enduring trait ties into societal behaviors and is linked to psychiatric and metabolic conditions. Despite its multifaceted nature, prior research has treated chronotype as a monolithic trait across the population, risking overlooking substantial heterogeneity in neural and behavioral fingerprints. To uncover hidden subgroups, we develop a supervised pattern-learning framework integrating three complementary brain-imaging modalities with deep behavioral and health profiling from 27,030 UK Biobank participants. We identify five distinct, biologically valid chronotype subtypes. Each demonstrates unique patterns across brain, behavioral and health profiles. External validation in 10,550 US children from the ABCD Study cohort reveals reversed age distributions and replicates sex-associated brain-behavioral patterns, suggesting that potential divergences between chronotype traits observed throughout adulthood may begin to emerge early in life. These findings highlight underappreciated sources of population variation that echo the rhythm of people's inner clock.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40246996,

title = {Multimodal population study reveals the neurobiological underpinnings of chronotype},

author = {Le Zhou and Karin Saltoun and Julie Carrier and Kai-Florian Storch and Robin I M Dunbar and Danilo Bzdok},

doi = {10.1038/s41562-025-02182-w},

issn = {2397-3374},

year  = {2025},

date = {2025-04-01},

journal = {Nat Hum Behav},

abstract = {The rapid shifts in society have altered human behavioural patterns, with increased evening activities, increased screen time and changed sleep schedules. As an explicit manifestation of circadian rhythms, chronotype is closely intertwined with physical and mental health. Night owls often exhibit unhealthier lifestyle habits, are more susceptible to mood disorders and have poorer physical fitness compared with early risers. Although individual differences in chronotype yield varying consequences, their neurobiological underpinnings remain elusive. Here we conducted a pattern-learning analysis with three brain-imaging modalities (grey matter volume, white-matter integrity and functional connectivity) and capitalized on 976 phenotypes in 27,030 UK Biobank participants. The resulting multilevel analysis reveals convergence on the basal ganglia, limbic system, hippocampus and cerebellum. The pattern derived from modelling actigraphy wearables data of daily movement further highlighted these key brain features. Overall, our population-level study comprehensively investigates chronotype, emphasizing its close connections with habit formation, reward processing and emotional regulation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39967311,

title = {The Deubiquitinase USP2 Modulates Photic Entrainment of the Circadian Clock at the Level of the Suprachiasmatic Nucleus},

author = {Shashank B Srikanta and Thomas W Brown and Antoine Malescot and Marie-Ève Cloutier and Lei Zhu and Christine Coutanson and Maryam Malki and Kai-Florian Storch and Ravi Rungta and Michel Cayouette and Ouria Dkhissi-Benyahya and Nicolas Cermakian},

doi = {10.1111/jnc.70018},

issn = {1471-4159},

year  = {2025},

date = {2025-02-01},

journal = {J Neurochem},

volume = {169},

number = {2},

pages = {e70018},

abstract = {Ubiquitin-specific peptidase 2 (USP2) is a deubiquitinase (DUB) with a diversity of functions in physiology. One of these functions is the regulation of circadian rhythms, which are physiological rhythms with a period of ~24 h. Previous studies have indicated a role for USP2 in photic entrainment, the process by which circadian clocks synchronize to environmental light cues. Here, we investigated the implication of USP2 in this process, using Usp2 knockout (KO) mice. Using different light treatments and running wheel recordings, we established that USP2 controls entrainment of the clock to light cues at dusk. Further, we showed that Usp2 is expressed throughout the suprachiasmatic nucleus (SCN), the site of the central clock, and in the retina. This raised the question of where USP2 acts on circadian photoreception. We found that it is not within the retina, as retinas of Usp2 KO mice have an intact structure and unaltered photoreception through intrinsically photosensitive retinal ganglion cells. Moreover, KO of Usp2 within the retina does not alter clock entrainment to light. In contract, KO of Usp2 in the SCN causes a light entrainment phenotype similar to full-body KO mice, showing that the action of USP2 in modulating photic entrainment predominantly takes place in the SCN. Finally, within the SCN, we found that induction of clock gene Per1 and activation of MAPK/ERK pathway in response to light were blunted in Usp2 KO mice. Altogether, we established a key role for USP2 in regulating photic entrainment by modulating light-responsive pathways within the SCN.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39742489,

title = {Mesolimbic dopamine neurons drive infradian rhythms in sleep-wake and heightened activity state},

author = {Pratap S Markam and Clément Bourguignon and Lei Zhu and Bridget Ward and Martin Darvas and Paul V Sabatini and Maia V Kokoeva and Bruno Giros and Kai-Florian Storch},

doi = {10.1126/sciadv.ado9965},

issn = {2375-2548},

year  = {2025},

date = {2025-01-01},

journal = {Sci Adv},

volume = {11},

number = {1},

pages = {eado9965},

abstract = {Infradian mood and sleep-wake rhythms with periods of 48 hours and beyond have been observed in patients with bipolar disorder (BD), which even persist in the absence of exogenous timing cues, indicating an endogenous origin. Here, we show that mice exposed to methamphetamine in drinking water develop infradian locomotor rhythms with periods of 48 hours and beyond which extend to sleep length and manic state-associated behaviors in support of a model for cycling in BD. The cycling capacity is abrogated upon genetic disruption of dopamine (DA) production in DA neurons of the ventral tegmental area (VTA) or ablation of nucleus accumbens projecting DA neurons. Furthermore, chemogenetic activation of DA neurons including those that project to the nucleus accumbens led to locomotor period lengthening in circadian clock-deficient mice, which was counteracted by antipsychotic treatment. Together, our findings argue that BD cycling relies on infradian rhythm generation that depends on mesolimbic DA neurons.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36979445,

title = {Behavioral and Transcriptomic Changes Following Brain-Specific Loss of Noradrenergic Transmission},

author = {Elsa Isingrini and Chloé Guinaudie and Léa Perret and Elisa Guma and Victor Gorgievski and Ian D Blum and Jessica Colby-Milley and Maryia Bairachnaya and Sébastien Mella and Antoine Adamantidis and Kai-Florian Storch and Bruno Giros},

doi = {10.3390/biom13030511},

issn = {2218-273X},

year  = {2023},

date = {2023-03-01},

journal = {Biomolecules},

volume = {13},

number = {3},

abstract = {Noradrenaline (NE) plays an integral role in shaping behavioral outcomes including anxiety/depression, fear, learning and memory, attention and shifting behavior, sleep-wake state, pain, and addiction. However, it is unclear whether dysregulation of NE release is a cause or a consequence of maladaptive orientations of these behaviors, many of which associated with psychiatric disorders. To address this question, we used a unique genetic model in which the brain-specific vesicular monoamine transporter-2 (VMAT2) gene expression was removed in NE-positive neurons disabling NE release in the entire brain. We engineered VMAT2 gene splicing and NE depletion by crossing floxed VMAT2 mice with mice expressing the Cre-recombinase under the dopamine β-hydroxylase (DBH) gene promotor. In this study, we performed a comprehensive behavioral and transcriptomic characterization of the VMAT2DBHcre KO mice to evaluate the role of central NE in behavioral modulations. We demonstrated that NE depletion induces anxiolytic and antidepressant-like effects, improves contextual fear memory, alters shifting behavior, decreases the locomotor response to amphetamine, and induces deeper sleep during the non-rapid eye movement (NREM) phase. In contrast, NE depletion did not affect spatial learning and memory, working memory, response to cocaine, and the architecture of the sleep-wake cycle. Finally, we used this model to identify genes that could be up- or down-regulated in the absence of NE release. We found an up-regulation of the synaptic vesicle glycoprotein 2c (SV2c) gene expression in several brain regions, including the locus coeruleus (LC), and were able to validate this up-regulation as a marker of vulnerability to chronic social defeat. The NE system is a complex and challenging system involved in many behavioral orientations given it brain wide distribution. In our study, we unraveled specific role of NE neurotransmission in multiple behavior and link it to molecular underpinning, opening future direction to understand NE role in health and disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34129812,

title = {Leptin receptor-expressing pericytes mediate access of hypothalamic feeding centers to circulating leptin},

author = {Liliia I Butiaeva and Tal Slutzki and Hannah E Swick and Clément Bourguignon and Sarah C Robins and Xiaohong Liu and Kai-Florian Storch and Maia V Kokoeva},

doi = {10.1016/j.cmet.2021.05.017},

issn = {1932-7420},

year  = {2021},

date = {2021-07-01},

journal = {Cell Metab},

volume = {33},

number = {7},

pages = {1433--1448.e5},

abstract = {Knowledge of how leptin receptor (LepR) neurons of the mediobasal hypothalamus (MBH) access circulating leptin is still rudimentary. Employing intravital microscopy, we found that almost half of the blood-vessel-enwrapping pericytes in the MBH express LepR. Selective disruption of pericytic LepR led to increased food intake, increased fat mass, and loss of leptin-dependent signaling in nearby LepR neurons. When delivered intravenously, fluorescently tagged leptin accumulated at hypothalamic LepR pericytes, which was attenuated upon pericyte-specific LepR loss. Because a paracellular tracer was also preferentially retained at LepR pericytes, we pharmacologically targeted regulators of inter-endothelial junction tightness and found that they affect LepR neuronal signaling and food intake. Optical imaging in MBH slices revealed a long-lasting, tonic calcium increase in LepR pericytes in response to leptin, suggesting pericytic contraction and vessel constriction. Together, our data indicate that LepR pericytes facilitate localized, paracellular blood-brain barrier leaks, enabling MBH LepR neurons to access circulating leptin.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33152385,

title = {Effects of antipsychotics on circadian rhythms in humans: a systematic review and meta-analysis},

author = {Eunsoo Moon and Paola Lavin and Kai-Florian Storch and Outi Linnaranta},

doi = {10.1016/j.pnpbp.2020.110162},

issn = {1878-4216},

year  = {2021},

date = {2021-06-01},

journal = {Prog Neuropsychopharmacol Biol Psychiatry},

volume = {108},

pages = {110162},

abstract = {Antipsychotics are widely used to treat psychiatric illness and insomnia. However, the etiology of insomnia is multifactorial, including disrupted circadian rhythms. Several studies show that antipsychotics might modulate even healthy circadian rhythms. The purpose of this systematic review is to integrate current knowledge about the effects of antipsychotics on the circadian rhythms in humans, and to conduct a meta- analysis with the available data. Nine electronic databases were searched. We followed the PRISMA guidelines and included randomized controlled trials (RCTs), non-RCTs, case-control studies, case series, and case reports. Of 7,217 articles, 70 were included. The available data was mainly from healthy individuals, or patients having schizophrenia, but the findings showed a transdiagnostic impact on circadian parameters. This was consistently seen as decreased amplitude of cortisol, melatonin, and body temperature. Particularly, a meta-analysis of 16 RCTs measuring cortisol rhythm showed that antipsychotics, especially atypical antipsychotics, decreased the cortisol area under the curve and morning cortisol level, compared to placebo. The data with melatonin or actigraphy was limited. Overall, this evidence about the circadian effect of antipsychotics showed a need for longitudinal, real-time monitoring of specific circadian markers to differentiate a change in amplitude from a shift in phasing, and for knowledge about optimal timing of administration of antipsychotics, according to individual baseline circadian parameters. Standardizing selection criteria and outcome methods could facilitate good quality intervention studies and evidence-based treatment guidelines. This is relevant considering the accumulating evidence of the high prevalence and unfavorable impact of disrupted circadian rhythms in psychiatric disorders.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid30873919,

title = {Irregular eating patterns associate with hypomanic symptoms in bipolar disorders},

author = {Asli Buyukkurt and Clément Bourguignon and Christina Antinora and Elisabeth Farquhar and Xiaoya Gao and Eloise Passarella and Duncan Sibthorpe and Karine Gou and Sybille Saury and Serge Beaulieu and Kai-Florian Storch and Outi Linnaranta},

doi = {10.1080/1028415X.2019.1587136},

issn = {1476-8305},

year  = {2021},

date = {2021-01-01},

journal = {Nutr Neurosci},

volume = {24},

number = {1},

pages = {23--34},

abstract = { We present novel dimensional methods to describe the timing of eating in psychopathology. We focused on the relationship between current mood in bipolar disorder (BD) and the stability of the temporal pattern of daily eating events.  Consenting BD patients ( = 69) from an outpatient, tertiary care clinic completed hourly charts of mood and eating for two weeks. Mood was also evaluated with Montgomery-Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS).  Illustrative displays, or eatograms, enabling visualization of all recorded eating events were used to guide assessment of the temporal structure of eating across the two week assessment period. We computed indices to quantify irregularities in timing of eating, namely I, I and I for the variability of frequency, timing, and interval of eating events, respectively. In this cohort, irregular temporal pattern of eating correlated with hypomanic symptoms (YMRS with I, Spearman rank order rh = 0.28,  = .019, with I, rh = 0.44,  < .001, and with I rh = 0.38,  = .001), but not depressive symptoms or anthropometric measures. : Our data suggest a link between the instability of the temporal order of daily eating and mood. The dimensional measures for eating pattern introduced here enable future investigations of correlations with psychopathology.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33184223,

title = {The core clock transcription factor BMAL1 drives circadian β-cell proliferation during compensatory regeneration of the endocrine pancreas},

author = {Volodymyr Petrenko and Miri Stolovich-Rain and Bart Vandereycken and Laurianne Giovannoni and Kai-Florian Storch and Yuval Dor and Simona Chera and Charna Dibner},

doi = {10.1101/gad.343137.120},

issn = {1549-5477},

year  = {2020},

date = {2020-12-01},

journal = {Genes Dev},

volume = {34},

number = {23-24},

pages = {1650--1665},

abstract = {Circadian clocks in pancreatic islets participate in the regulation of glucose homeostasis. Here we examined the role of these timekeepers in β-cell regeneration after the massive ablation of β cells by doxycycline-induced expression of diphtheria toxin A (DTA) in Insulin-rtTA/TET-DTA mice. Since we crossed reporter genes expressing α- and β-cell-specific fluorescent proteins into these mice, we could follow the fate of α- and β cells separately. As expected, DTA induction resulted in an acute hyperglycemia, which was accompanied by dramatic changes in gene expression in residual β cells. In contrast, only temporal alterations of gene expression were observed in α cells. Interestingly, β cells entered S phase preferentially during the nocturnal activity phase, indicating that the diurnal rhythm also plays a role in the orchestration of β-cell regeneration. Indeed, in arrhythmic -deficient mice, which lack circadian clocks, no compensatory β-cell proliferation was observed, and the β-cell ablation led to aggravated hyperglycemia, hyperglucagonemia, and fatal diabetes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32856463,

title = {Suicidal Ideation and Insomnia in Bipolar Disorders: Idéation suicidaire et insomnie dans les troubles bipolaires},

author = {Lia Bertrand and Clément Bourguignon and Serge Beaulieu and Kai-Florian Storch and Outi Linnaranta},

doi = {10.1177/0706743720952226},

issn = {1497-0015},

year  = {2020},

date = {2020-11-01},

journal = {Can J Psychiatry},

volume = {65},

number = {11},

pages = {802--810},

abstract = {OBJECTIVE: Bipolar disorder (BD) confers elevated suicide risk and associates with misaligned circadian rhythm. Real-time monitoring of objectively measured sleep is a novel approach to detect and prevent suicidal behavior. We aimed at understanding associations between subjective insomnia and actigraphy data with severity of suicidal ideation in BDs.nnMETHODS: This prospective cohort study comprised 76 outpatients with a BD aged 18 to 65 inclusively. Main measures included 10 consecutive days of wrist actigraphy; the Athens Insomnia Scale (AIS); the Montgomery-Åsberg Depression Rating Scale (MADRS); the Quick Inventory of Depressive Symptoms-16, self-rating (QIDS-SR-16); and the Columbia Suicide Severity Rating Scale. Diagnoses, medications, and suicide attempts were obtained from chart review.nnRESULTS: Suicidal ideation correlated moderately with subjective insomnia (AIS with QIDS-SR-16 item 12 ρ =0.26,  = 0.03; MADRS item 10 ρ = 0.33,  = 0.003). Graphical sleep patterns showed that suicidal patients were enriched among the most fragmented sleep patterns, and this was confirmed by correlations of suicidal ideation with actigraphy data at 2 visits. Patients with lifetime suicide attempts ( = 8) had more varied objective sleep (a higher standard deviation of center of daily inactivity [0.64 vs. 0.26,  = 0.01], consolidation of daily inactivity [0.18 vs. 0.10,  = <0.001], sleep offset [3.02 hours vs. 1.90 hours,  = <0.001], and total sleep [105 vs. 69 minutes,  = 0.02], and a lower consolidation of daily inactivity [0.65 vs. 0.79,  = 0.03]).nnCONCLUSIONS: Subjective insomnia, a nonstigmatized symptom, can complement suicidality screens. Longer follow-ups and larger samples are warranted to understand whether real-time sleep monitoring predicts suicidal ideation in patient subgroups or individually.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32232937,

title = {Inactograms and objective sleep measures as means to capture subjective sleep problems in patients with a bipolar disorder},

author = {Paola Lavin-Gonzalez and Clément Bourguignon and Olivia Crescenzi and Serge Beaulieu and Kai-Florian Storch and Outi Linnaranta},

doi = {10.1111/bdi.12903},

issn = {1399-5618},

year  = {2020},

date = {2020-11-01},

journal = {Bipolar Disord},

volume = {22},

number = {7},

pages = {722--730},

abstract = {BACKGROUND: Sleep problems are common in bipolar disorders (BDs). To objectively characterize these problems in BDs, further methodological development is needed to capture subjective insomnia.nnAIM: To test psychometric properties of the Athens Insomnia Scale (AIS), and associations with actigraphy-derived measures, applying modifications in actigraphy data processing to capture features of perturbed sleep in patients with a BD.nnMETHODS: Seventy-four patients completed the AIS and the Quick Inventory of Depressive Symptomatology, self-report (QIDS-SR-16). Locomotor activity was continuously recorded by wrist actigraphy for ≥10 consecutive days. We computed the sleep onset/offset, the center of daily inactivity (CenDI), as a proxy for chronotype, and the degree of consolidation of daily inactivity (ConDI), as a proxy for sleep-wake rhythm strength.nnRESULTS: AIS showed good psychometric properties (Cronbach's alpha = 0.84; test-retest correlation = 0.84, P<.001). Subjective sleep problems correlated moderately with a later sleep phase (CenDI with AIS rho = 0.34, P = .003), lower consolidation (ConDI with AIS rho = -0.22, P = .05; with QIDS-SR-16 rho = -0.27, P = .019), later timing of sleep offset (with AIS rho = 0.49, P = ≤.001, with QIDS-SR-16 rho = 0.36, P = .002), and longer total sleep (with AIS rho = 0.29, P = .012, with QIDS-SR-16 rho = 0.41, P = ≤.001). While AIS was psychometrically more solid, correlations with objective sleep were more consistent across time for QIDS-SR-16.nnCONCLUSIONS: AIS and QIDS-SR-16 are suitable for clinical screening of sleep problems among patients with a BD. Subjective insomnia associated with objective measures. For clinical and research purposes, actigraphy and data visualization on inactograms are useful for accurate longitudinal characterization of sleep patterns.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32211873,

title = {Late and Instable Sleep Phasing is Associated With Irregular Eating Patterns in Eating Disorders},

author = {Outi Linnaranta and Clément Bourguignon and Olivia Crescenzi and Duncan Sibthorpe and Asli Buyukkurt and Howard Steiger and Kai-Florian Storch},

doi = {10.1093/abm/kaaa012},

issn = {1532-4796},

year  = {2020},

date = {2020-09-01},

journal = {Ann Behav Med},

volume = {54},

number = {9},

pages = {680--690},

abstract = {BACKGROUND: Sleep problems are common in eating disorders (EDs).nnPURPOSE: We evaluated whether sleep-phasing regularity associates with the regularity of daily eating events.nnMETHODS: ED patients (n = 29) completed hourly charts of mood and eating occasions for 2 weeks. Locomotor activity was recorded continuously by wrist actigraphy for a minimum of 10 days, and sleep was calculated based on periods of inactivity. We computed the center of daily inactivity (CenDI) as a measure of sleep phasing and consolidation of the daily inactivity (ConDI) as a measure of daily sleep rhythm strength. We assessed interday irregularities in the temporal structure of food intake using the standard deviation (SD) of frequency (IFRQ), timing (ITIM), and interval (IINT) of food intake. A self-evaluation of other characteristics included mood, anxiety, and early trauma.nnRESULTS: A later phasing of sleep associated with a lower frequency of eating (eating frequency with the CenDI rho = -0.49, p = .007). The phasing and rhythmic strength of sleep correlated with the degree of eating irregularity (CenDI with ITIM rho = 0.48, p = .008 and with IINT rho = 0.56, p = .002; SD of CenDI with ITIM rho = 0.47, p = .010, and SD of ConDI with IINT rho = 0.37, p = .048). Childhood Trauma Questionnaire showed associations with variation of sleep onset (rho = -0.51, p = .005) and with IFRQ (rho = 0.43, p = .023).nnCONCLUSIONS: Late and variable phasing of sleep associated robustly with irregular pattern of eating. Larger data sets are warranted to enable the analysis of diagnostic subgroups, current medication, and current symptomatology and to confirm the likely bidirectional association between eating pattern stability and the timing of sleep.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32523515,

title = {Ultradian Secretion of Growth Hormone in Mice: Linking Physiology With Changes in Synapse Parameters Using Super-Resolution Microscopy},

author = {Klaudia Bednarz and Walaa Alshafie and Sarah Aufmkolk and Théotime Desserteaux and Pratap Singh Markam and Kai-Florian Storch and Thomas Stroh},

doi = {10.3389/fncir.2020.00021},

issn = {1662-5110},

year  = {2020},

date = {2020-01-01},

journal = {Front Neural Circuits},

volume = {14},

pages = {21},

abstract = {Neuroendocrine circuits are orchestrated by the pituitary gland in response to hypothalamic hormone-releasing and inhibiting factors to generate an ultradian and/or circadian rhythm of hormone secretion. However, mechanisms that govern this rhythmicity are not fully understood. It has been shown that synaptic transmission in the rodent hypothalamus undergoes cyclical changes in parallel with rhythmic hormone secretion and a growing body of evidence suggests that rapid rewiring of hypothalamic neurons may be the source of these changes. For decades, structural synaptic studies have been utilizing electron microscopy, which provides the resolution suitable for visualizing synapses. However, the small field of view, limited specificity and manual analysis susceptible to bias fuel the search for a more quantitative approach. Here, we apply the fluorescence super-resolution microscopy approach  Stochastic Optical Reconstruction Microscopy (STORM) to quantify and structurally characterize excitatory and inhibitory synapses that contact growth hormone-releasing-hormone (GHRH) neurons during peak and trough values of growth hormone (GH) concentration in mice. This approach relies on a three-color immunofluorescence staining of GHRH and pre- and post-synaptic markers, and a quantitative analysis with a Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm. With this method we confirm our previous findings, using electron microscopy, of increased excitatory synaptic input to GHRH neurons during peak levels of GH. Additionally, we find a shift in synapse numbers during low GH levels, where more inhibitory synaptic inputs are detected. Lastly, we utilize STORM to study novel aspects of synaptic structure. We show that more excitatory (but not inhibitory) pre-synaptic clusters associate with excitatory post-synaptic clusters during peaks of GH secretion and that the numbers of post-synaptic clusters increase during high hormone levels. The results presented here provide an opportunity to highlight STORM as a valuable quantitative approach to study synaptic structure in the neuroendocrine circuit. Importantly, our analysis of GH circuitry sheds light on the potential mechanism that drives ultradian changes in synaptic transmission and possibly aids in GH pulse generation in mice.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31522764,

title = {The eIF2α Kinase GCN2 Modulates Period and Rhythmicity of the Circadian Clock by Translational Control of Atf4},

author = {Salil Saurav Pathak and Dong Liu and Tianbao Li and Nuria de Zavalia and Lei Zhu and Jin Li and Ramanujam Karthikeyan and Tommy Alain and Andrew C Liu and Kai-Florian Storch and Randal J Kaufman and Victor X Jin and Shimon Amir and Nahum Sonenberg and Ruifeng Cao},

doi = {10.1016/j.neuron.2019.08.007},

issn = {1097-4199},

year  = {2019},

date = {2019-11-01},

journal = {Neuron},

volume = {104},

number = {4},

pages = {724--735.e6},

abstract = {The integrated stress response (ISR) is activated in response to diverse stress stimuli to maintain homeostasis in neurons. Central to this process is the phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α). Here, we report a critical role for ISR in regulating the mammalian circadian clock. The eIF2α kinase GCN2 rhythmically phosphorylates eIF2α in the suprachiasmatic circadian clock. Increased eIF2α phosphorylation shortens the circadian period in both fibroblasts and mice, whereas reduced eIF2α phosphorylation lengthens the circadian period and impairs circadian rhythmicity in animals. Mechanistically, phosphorylation of eIF2α promotes mRNA translation of Atf4. ATF4 binding motifs are identified in multiple clock genes, including Per2, Per3, Cry1, Cry2, and Clock. ATF4 binds to the TTGCAGCA motif in the Per2 promoter and activates its transcription. Together, these results demonstrate a significant role for ISR in circadian physiology and provide a potential link between dysregulated ISR and circadian dysfunction in brain diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}