Biology subjects

Foustoukos, G.

Publications and source records attributed to Foustoukos, G..

7 recordsLinked to original sources

bioRxiv2026

High-throughput serial two-photon tomography with BakingTray and BrainSaw

Volumetric imaging is increasingly important in fields such as neuroscience, where quantifying structure and mapping features are inherently three-dimensional problems. Block-face serial two-photon tomography (STPT) has emerged as a powerful approach for high-resolution, whole-organ volumetric imaging. STPT avoids complex sample preparation and balances image quality, speed, and scalability. However, STPT remains niche, in part because of the absence of flexible, general-purpose control software. Here we present BakingTray, an open-source software platform for STPT that extends ScanImage. BakingTrays modular framework accommodates diverse hardware configurations and allows users to build systems customised to their needs. Twelve such systems, which we call BrainSaws, have been constructed worldwide since 2016, with more under construction, and have so far contributed to 35 research papers. The three systems at the Sainsbury Wellcome Centre alone have acquired over 7,000 samples in a busy multi-user facility. We demonstrate the platform across its core neuroscience applications: electrode track localisation, brain-wide cell counting, and bulk projection mapping. Beyond these, we map the cell-type-specific synaptic output of inhibitory neurons in the ventral lateral geniculate nucleus and, with whole-mount staining, amyloid plaques brain-wide in a mouse model of Alzheimers disease. BakingTray is a mature platform for groups or facilities needing a customised volumetric imaging solution, whether built new or converted cheaply from an existing two-photon microscope.

neuroscience↗

bioRxiv2026

Rapid cortical reorganization tracks goal-directed sensorimotor learning in real time

Sensorimotor associations are typically thought to require days of training to consolidate in sensory cortex, yet adaptive behavior can emerge within minutes. Here, we developed a barrel cortex-dependent whisker-based detection task in which mice learned to associate a novel tactile whisker stimulus with reward within a single behavioral session. Longitudinal two-photon calcium imaging of layer 2/3 barrel cortex neurons revealed that reward-driven learning rapidly reorganized the neuronal representation of the whisker deflection within a single session. Population decoding tracked this transition trial-by-trial during learning with neuronal trajectories mirroring behavior. Critically, neurons that gained stimulus responsiveness across training preferentially took part in spontaneous reactivation events during learning, suggesting that online reactivations could act as a potential upstream selection mechanism. Our results suggest that reward-based learning evokes rapid sensory cortical reorganization on the timescale of minutes, which could be mediated by a concurrent reactivation-based mechanism driving plasticity.

neuroscience↗

bioRxiv2026

A Conserved Locus Coeruleus fMRI Signature of Brain-State Transitions across Sleep, Anesthesia, and Wakefulness

Neuromodulatory systems dynamically reconfigure large-scale brain networks to support adaptation across behavioral and cognitive states. The locus coeruleus (LC), which broadcasts noradrenaline throughout the forebrain, is a central regulator of arousal and state-dependent dynamics. However, how LC activity manifests in brain-wide organization across physiological contexts, and how it biases fMRI connectivity, remains poorly understood. Using an optogenetically informed cross-species framework, we identify a transient LC-derived spatiotemporal pattern of brain activity accompanying brain-state transitions under progressively naturalistic conditions: controlled LC stimulation and endogenous LC fluctuations in anesthetized mice, sleep-wake transitions in rodents and humans, and resting-state activity in awake humans. This LC-derived signature is conserved across species and contexts, leaving a robust and detectable imprint on the BOLD signal. Critically, the prevalence of LC events systematically biases functional connectivity metrics in human fMRI. These findings establish LC activity as a mechanistically interpretable source of variability in resting-state measurements, with direct implications for the interpretation of fMRI biomarkers in arousal-related disorders.

neuroscience↗

bioRxiv2025

Vagal afferent activation induces a NREM-sleep-like state with brain-body cooling, but locus coeruleus activation

Parasympathetic nervous system activity, vital for restorative sleep, is influenced by vagal sensory afferents, but how these shape brain-body correlates of sleep remains open. We investigated this by combining vagal sensory neuron (VSN) stimulation with EEG/EMG, heart rate, brain-body temperature, and noradrenergic locus coeruleus (LC) neuron population activity measures. Opto-/chemogenetic VSN manipulations in Vglut2-Cre mice were validated via in vitro synaptic physiology, cFos expression, and heart rate measures. Chemogenetic VSN stimulation during the resting phase induced a non-rapid-eye-movement sleep (NREMS)-like state with enriched, but homeostatically regulated, low-frequency (0.75-4 Hz) EEG activity, yet suppressed REMS. Simultaneously, brain-body temperatures dropped while LC activity increased. Recovery was gradual towards normal NREMS-REMS-cycles but accelerated by external warming, identifying cooling as key factor. We conclude that VSN activation can promote brain-body correlates as a continuum of normal NREM sleep while engaging forebrain neuromodulation, offering insights into mechanisms of sleep disruptions linked to autonomic dysregulation.

neuroscience↗

bioRxiv2023

Locus coeruleus activity fluctuations set a non-reducible timeframe for mammalian NREM-REM sleep cycles

The noradrenergic locus coeruleus (LC) is vital for brain states underlying wakefulness, whereas its roles for sleep remain uncertain. Combining mouse sleep-wake monitoring, behavioral manipulations, LC fiber photometry and closed-loop optogenetics, we found that LC neuronal activity partitioned non-rapid-eye-movement sleep (NREMS) into alternating brain and autonomic states that rule the NREMS-REMS cycle. High LC activity levels generated an autonomic-subcortical arousal state that facilitated cortical microarousals, while low levels were obligatory for REMS entries. Timed optogenetic LC inhibition revealed that this functional alternation set the duration of the NREMS-REMS cycle by ruling REMS entries during undisturbed sleep and when pressure for REMS was high. A stimulus-enriched, stress-promoting wakefulness increased high LC activity levels at the expense of low ones in subsequent NREMS, fragmenting NREMS through microarousals and delaying REMS onset. We conclude that LC activity fluctuations gatekeep the NREM-REMS cycle over recurrent infraslow intervals, but they also convey vulnerability to adverse wake experiences.

neuroscience↗

bioRxiv2022

Learning-related congruent and incongruent changes of excitation and inhibition in distinct cortical areas

Excitatory and inhibitory neurons in diverse cortical regions are likely to contribute differentially to the transformation of sensory information into goal-directed motor plans. Here, we investigate the relative changes across mouse sensorimotor cortex in the activity of putative excitatory and inhibitory neurons - categorized as regular or fast spiking according to their action potential waveform - comparing before and after learning of a whisker detection task with delayed licking as perceptual report. Surprisingly, we found that the whisker-evoked activity of regular versus fast spiking neurons changed in opposite directions after learning in primary and secondary whisker motor cortices, while it changed similarly in primary and secondary orofacial motor cortices. Our results suggest that changes in the balance of excitation and inhibition in local circuits concurrent with changes in the long-range synaptic inputs in distinct cortical regions might contribute to performance of delayed sensory-to-motor transformation.

neuroscience↗

bioRxiv2020

Divergent sensory processing converges in frontal cortex for a planned motor response

The neuronal mechanisms generating a delayed motor response initiated by a sensory cue remain elusive. Here, we tracked the precise sequence of cortical activity in mice transforming a brief whisker stimulus into delayed licking using wide-field calcium imaging, multi-region high-density electrophysiology and time-resolved optogenetic manipulation. Rapid activity evoked by whisker deflection acquired two prominent features for task performance: i) an enhanced excitation of secondary whisker motor cortex, suggesting its important role connecting whisker sensory processing to lick motor planning, and ii) a transient reduction of activity in orofacial sensorimotor cortex, which contributed to suppressing premature licking. Subsequent widespread cortical activity during the delay period largely correlated with anticipatory movements, but when these were accounted for, a focal sustained activity remained in frontal cortex, which was causally essential for licking in the response period. Our results demonstrate key cortical nodes for motor plan generation and timely execution in delayed goal-directed licking.

neuroscience↗