Biology subjects

Humphrey, C.

Publications and source records attributed to Humphrey, C..

5 recordsLinked to original sources

bioRxiv2025

Interneuron theta phase locking controls seizure susceptibility

The timing of neuronal activity is highly precise and often organized by brain-wide oscillations. Many neurons modulate their firing rates at specific phases of theta (known as theta phase locking), creating discrete windows for information processing. Disrupted theta phase locking has been found across several neurological and psychiatric disorders (e.g., epilepsy), but gaps in technology have prevented its causal influence from being tested. Here, we developed PhaSER, a closed-loop optogenetic system designed to control the phase locking of specific interneurons, and demonstrate a causal role for inhibitory phase locking in seizure susceptibility. We first found that parvalbumin (PV+) and somatostatin (SOM+) expressing interneurons in the dentate gyrus (DG) show distinct theta phase locking profiles and are differentially impacted in a mouse model of chronic temporal lobe epilepsy. In healthy mice, PV+ interneurons have extremely consistent phase-locked firing near the trough of CA1 theta, aligned with excitatory inputs to DG. However, in epileptic mice, PV+ interneuron activity is dispersed across the theta cycle, suggesting that altered inhibitory phase locking could be a causal mediator of seizure susceptibility in epilepsy. To test this hypothesis, we applied PhaSER to directly control the phase locking of DG interneurons during an acute test of seizure susceptibility. In epileptic mice, re-aligning DG PV+ interneuron theta phase locking reduced seizure susceptibility, while in healthy mice, disrupting normal phase locking of PV+ interneurons increased seizure susceptibility. Together, this provides the first causal evidence that inhibitory theta phase locking can directly control network function by shifting seizure susceptibility in the healthy and epileptic brain.

neuroscience↗

bioRxiv2024

Controlled 'out-of-season' spawning of reef-forming corals in aquaria using offset environmental profiles

The global climate crisis has heightened the urgency for developing interventions to enhance resilience and recovery of coral reef ecosystems. However, research programs are often bottlenecked by availability of coral early life stage material due to the seasonal (annual) nature of coral mass spawning events. Here, we present a proof-of-concept of "out-of-season" coral spawning, utilising advanced aquarium control technology to induce spawning in multiple key Great Barrier Reef (GBR) coral species held in long-term indoor aquaria. By developing a 6-month offset environmental profile encompassing seasonal temperature, photoperiod, and lunar profiles, we successfully induced synchronised mass coral spawning during austral autumn/winter (May - June) over consecutive years in 2022 and 2023. We also "phase-shifted" the hour of sunset by five hours on spawning nights, creating a more favourable time window (i.e., minimising late nights) for gamete fertilisation. The timing of gamete release in captive corals closely matched previous GBR field observations for both nights after full moon (NAFM) and time after sunset (TAS). Gamete fertilisation was successful for six GBR species: Acropora millepora, Acropora loripes, Acropora hyacinthus, Acropora elseyi, Acropora austera, and Montipora aequituberculata producing a total of 1.75 million larvae. We outline key physiological insights gained into environmental regulation of coral spawning synchronicity and discuss the potential for out-of-season spawning to accelerate various aspects of coral reproduction research and enhance the growing toolbox of active restoration strategies aimed at reversing global coral reef decline.

ecology↗

bioRxiv2023

Nanodelivery of lipids to coral larvae maximises post-settlement survival: Implications for larval ecology and reef restoration.

Interest in reef restoration is increasing as coral mortality has accelerated at an unprecedented rate. However, high mortality rates of coral early-life stages represent a population bottleneck, which directly impacts the effectiveness of restoration projects. While most coral larvae are considered lecithotrophic and catabolise maternally transmitted lipids to meet metabolic demands; here we demonstrate that coral larvae can be facultative feeders. We used nanoparticles to deliver triacylglycerides to aposymbiotic larvae which resulted in a 30% increase in larval energetic lipids, and a 46% increase in survival rate, up to 16 weeks post-settlement. Changes in phospholipid molecular species in the larvae suggest phagocytosis of the nanoparticles, and an increase in free fatty acids indicates lipolysis of the phagocytosed triacylglycerides. We suggest that a continuum of nutritional strategies should be recognised in coral early-life stages, and that nanoparticles can be used by restoration practitioners to deliver nutritional resources to maximise restoration outcomes.

ecology↗

bioRxiv2023

Manipulating single-unit theta phase-locking with PhaSER: An open-source tool for real-time phase estimation and manipulation

The precise timing of neuronal spiking relative to the brains endogenous oscillations (i.e., phase-locking or spike-phase coupling) has long been hypothesized to coordinate cognitive processes and maintain excitatory-inhibitory homeostasis. Indeed, disruptions in theta phase-locking have been described in models of neurological diseases with associated cognitive deficits and seizures, such as Alzheimers disease, temporal lobe epilepsy, and autism spectrum disorders. However, due to technical limitations, determining if phase-locking causally contributes to these disease phenotypes has not been possible until recently. To fill this gap and allow for the flexible manipulation of single-unit phase-locking to on-going endogenous oscillations, we developed PhaSER, an open-source tool that allows for phase-specific manipulations. PhaSER can deliver optogenetic stimulation at defined phases of theta in order to shift the preferred firing phase of neurons relative to theta in real-time. Here, we describe and validate this tool in a subpopulation of inhibitory neurons that express somatostatin (SOM) in the CA1 and dentate gyrus (DG) regions of the dorsal hippocampus. We show that PhaSER is able to accurately deliver a photo-manipulation that activates opsin+ SOM neurons at specified phases of theta in real-time in awake, behaving mice. Further, we show that this manipulation is sufficient to alter the preferred firing phase of opsin+ SOM neurons without altering the referenced theta power or phase. All software and hardware requirements to implement real-time phase manipulations during behavior are available online (https://github.com/ShumanLab/PhaSER).

neuroscience↗

bioRxiv2017

Functional genomic analysis of corals from natural CO2-seeps reveal core molecular responses involved in acclimatization to ocean acidification

Little is known about the potential for acclimatization or adaptation of corals to ocean acidification and even less about the molecular mechanisms underpinning these processes. Here we examine global gene expression patterns in corals and their intracellular algal symbionts from two replicate population pairs in Papua New Guinea that have undergone long-term acclimatization to natural variation in pCO2. In the coral host, only 61 genes were differentially expressed in response to pCO2 environment, but the pattern of change was highly consistent between replicate populations, likely reflecting the core expression homeostasis response to ocean acidification. Functional annotations highlight lipid metabolism and a change in the stress response capacity of corals as a key part of this process. Specifically, constitutive downregulation of molecular chaperones was observed, which may impact response to combined climate-change related stressors. Elevated CO2 has been hypothesized to benefit photosynthetic organisms but expression changes of in hospite Symbiodinium in response to acidification were greater and less consistent among reef populations. This population-specific response suggests hosts may need to adapt not only to an acidified environment, but also to changes in their Symbiodinium populations that may not be consistent among environments. This process adds another challenging dimension to the physiological process of coping with climate change.

genomics↗