Heterogeneous responses to embryonic critical period perturbations among different components of theDrosophilalarval locomotor circuit DOI
Niklas Krick,

Jacob Davies,

Bramwell Coulson

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 16, 2024

Abstract As developing neural circuits become functional, they undergo a phase of heightened plasticity in response to intrinsic and/or extrinsic stimuli. These developmental windows are termed critical periods (CPs), because perturbations during the CP can lead lasting and significant change subsequent development, such as sub-optimal unstable networks. By contrast, same manipulations before or after does not create changes. Here, we have used Drosophila larval locomotor network study how different identified, connected elements respond perturbation, from pre-motor interneuron motoneuron, neuromuscular junction. Using heat stress an ecologically relevant stimulus, show that increasing temperature causes increased activity that, when applied CP, leads larvae crawl more slowly require longer recover electroshock-induced seizures, indicative decreased stability. Within central nervous system, find perturbation interneurons delivering synaptic drive motoneurons, which turn display reduced excitability. The peripheral junction, on other hand, maintains normal transmission, despite structural changes terminal overgrowth altered postsynaptic receptor field composition. Overall, our data demonstrate within differentially perturbation. Our results suggest underlying sequence, hierarchy, adjustment CPs, present highly tractable experimental model system with biology.

Язык: Английский

Excitation/Inhibition balance relates to cognitive function and gene expression in temporal lobe epilepsy: a high density EEG assessment with aperiodic exponent DOI Creative Commons
Gian Marco Duma, Simone Cuozzo, Luc Wilson

и другие.

Brain Communications, Год журнала: 2024, Номер 6(4)

Опубликована: Янв. 1, 2024

Patients with epilepsy are characterized by a dysregulation of excitation/inhibition balance (E/I). The assessment E/I may inform clinicians during the diagnosis and therapy management, even though it is rarely performed. An accessible measure brain represents clinically relevant feature. Here, we exploited exponent aperiodic component power spectrum electroencephalography (EEG) signal, as non-invasive cost-effective proxy balance. We recorded resting-state activity high-density EEG from 67 patients temporal lobe 35 controls. extracted fit source-reconstructed tested differences between Spearman's correlation was performed clinical variables (age onset, duration neuropsychology) cortical expression epilepsy-related genes derived Allen Human Brain Atlas. showed significantly larger exponent, corresponding to inhibition-directed balance, in bilateral frontal regions. Lower left entorhinal dorsolateral prefrontal cortices corresponded lower performance short-term verbal memory. Limited epilepsy, detected significant

Язык: Английский

Процитировано

9

Serotonin acts through multiple cellular targets during an olfactory critical period. DOI Creative Commons
Ahana Mallick, Hua Tan, Jacob Epstein

и другие.

iScience, Год журнала: 2024, Номер 27(11), С. 111083 - 111083

Опубликована: Окт. 9, 2024

Язык: Английский

Процитировано

1

BK channel gain-of-function disrupts limb control by suppressing neurotransmission during a critical developmental window DOI Creative Commons
Simon A. Lowe, Abigail D. Wilson, Gabriel Aughey

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Сен. 22, 2023

SUMMARY Gain-of-function mutations in BK potassium channels (BK GOF) cause debilitating involuntary limb movements. modulate action potential shape and neurotransmission mature neurons, yet some GOF also neurodevelopmental morbidities. Thus, whether impairs control by altering the excitation/inhibition of motor circuits, or disrupting their development, remains unclear. To address this issue, we developed a genetic method enabling spatiotemporal channel expression neurons fruit fly, Drosophila . In concert with high-resolution measurements kinematics, demonstrate that act during narrow period to perturb adult flies. During period, alters synaptic localisation key active zone protein Bruchpilot suppresses excitatory neurotransmission. wild-type background, find reducing neural activity neurodevelopment yields similar defects those observed Conversely, enhancing excitability development rescues alterations kinematics Collectively, our results suggest perturbs largely activity-dependent aspects neuronal development.

Язык: Английский

Процитировано

3

Active microrheology with a single, time-shared laser trap DOI Creative Commons
Frederic Català-Castro, Santiago Ortiz-Vásquez, Carmen Martínez-Fernández

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Окт. 20, 2023

Abstract Recording the mechanical response of biological samples, cell’s interior and complex fluids in general, would enable deeper understanding cellular differentiation, ageing drug discovery. Here, we present a time-shared optical tweezer microrheology (TimSOM) pipeline to determine frequency- age-dependent viscoelastic properties materials. Our approach consists splitting single laser beam into two near-instantaneous traps carry out simultaneous force displacement measurements with sub-nanometer sub-picoNewton accuracy during sinusoidal perturbations. Leveraging numerical analytical models, find solutions commonly encountered deviations, build practical robust nanorheometer. We demonstrate versatility technique by 1) measuring phase transitions an biomolecular condensate, 2) quantifying three intracellular compartments zebrafish progenitor cells, and, 3) using Caenorhabditis elegans , uncover how mutations causing nuclear envelopathies soften cytosol intestinal cells organismal age. Together, our advances afford rapid phenotyping material inside proteins blends, opening avenues for biomedical screening applications.

Язык: Английский

Процитировано

2

Circadian control in the timing of critical periods duringDrosophilalarval neuronal development. DOI Creative Commons
Sarah J. Doran, Adam A. Bradlaugh,

Jack Corke

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 25, 2024

Abstract Critical periods (CPs) of development are temporal windows heightened neural plasticity. Activity perturbation during CPs can produce significant, and permanent, alterations to the circuits. In this study we report a circadian mechanism underlying timing in Drosophila embryonic larval development. These occur at ∼24 hr intervals open manipulation through blue light (BL)-activation regulator Cryptochrome (CRY). This is sufficient destabilize CNS, evidenced by an induced seizure phenotype when tested third instar (L3). addition CRY nulls, genetic ablation period gene also mitigates BL exposure and, moreover, alleles that affect alter CPs. Our analysis shows clear role for main clock neuropeptide, pigment dispersing factor (PDF), transduce output these Targeted PDF receptor knockdown, either GABAergic or CRY-positive neurons, prevent CRY-mediated phenotype. first demonstration larvae, whilst alone major significance, our results highlight potential using larvae as model investigate impact rhythms on early neuronal higher organisms, which remains experimentally challenging. Significance Statement Whilst biological well understood adult same not true How maternal impacts mammalian fetus poorly understood. Given many expectant mothers experience altered rhythms, largely due nightshift working, it important address concerns. Here identify clock-mediated be manipulated light. findings provide experimental opportunity better understand

Язык: Английский

Процитировано

0

Serotonin acts through multiple cellular targets during an olfactory critical period. DOI Creative Commons
Ahana Mallick, Hua Tan, Jacob Epstein

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 14, 2024

ABSTRACT Serotonin (5-HT) is known to modulate early development during critical periods when experience drives heightened levels of plasticity in neurons. Here, we take advantage the genetically tractable olfactory system Drosophila investigate how 5-HT modulates period CO2 sensing circuit fruit flies. Our study reveals that 5HT modulation multiple neuronal targets necessary for experience-dependent structural changes an odor processing circuit. The CPP involve local inhibitory networks and consistent with this found knocking down 5-HT7 receptors a subset GABAergic interneurons was sufficient block CPP, as GABA expressed by sensory neurons (OSNs). Additionally, direct OSNs via 5-HT2B expression cognate also essential CPP. Furthermore, 5-HT1B serotonergic required period.

Язык: Английский

Процитировано

0

OptoChamber: A Low-cost, Easy-to-Make, Customizable, and Multi-Chambered Electronic Device for Applying Optogenetic Stimulation to Larval DOI
Michael R. Kann,

Martin K Ackerman,

Sarah D. Ackerman

и другие.

PubMed, Год журнала: 2024, Номер 2024

Опубликована: Янв. 1, 2024

Optogenetics is a powerful tool used to manipulate physiological processes in animals through cell-specific expression of genetically modified channelrhodopsins. In

Язык: Английский

Процитировано

0

Heterogeneous responses to embryonic critical period perturbations among different components of theDrosophilalarval locomotor circuit DOI
Niklas Krick,

Jacob Davies,

Bramwell Coulson

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 16, 2024

Abstract As developing neural circuits become functional, they undergo a phase of heightened plasticity in response to intrinsic and/or extrinsic stimuli. These developmental windows are termed critical periods (CPs), because perturbations during the CP can lead lasting and significant change subsequent development, such as sub-optimal unstable networks. By contrast, same manipulations before or after does not create changes. Here, we have used Drosophila larval locomotor network study how different identified, connected elements respond perturbation, from pre-motor interneuron motoneuron, neuromuscular junction. Using heat stress an ecologically relevant stimulus, show that increasing temperature causes increased activity that, when applied CP, leads larvae crawl more slowly require longer recover electroshock-induced seizures, indicative decreased stability. Within central nervous system, find perturbation interneurons delivering synaptic drive motoneurons, which turn display reduced excitability. The peripheral junction, on other hand, maintains normal transmission, despite structural changes terminal overgrowth altered postsynaptic receptor field composition. Overall, our data demonstrate within differentially perturbation. Our results suggest underlying sequence, hierarchy, adjustment CPs, present highly tractable experimental model system with biology.

Язык: Английский

Процитировано

0