Biology subjects

Yaseen, H.

Publications and source records attributed to Yaseen, H..

3 recordsLinked to original sources

bioRxiv2026

Brain-derived ketone bodies can replace glucose to power neural function

The vertebrate brain is exquisitely sensitive to disruptions in glucose metabolism, and failure of adequate glucose delivery causes neurological dysfunction. Here, we discovered an animal with the capacity to defy this rule: We show that neural activity in frogs, animals with seemingly typical glucose demands, can stop metabolizing glucose by, in part, shifting to ketone bodies made exclusively within the brain after emergence from hibernation. This involves ketone body synthesis and transport from astrocytes to neurons to power synaptic transmission, along with the upregulation of gene expression that controls fatty acid catabolism and ketone body transport. Brain-derived ketone bodies also prevent decrements in activity that occur during hypoxia. These results provide insight into how frogs restart brain circuits following months of underwater hibernation when facing severe hypoxia and hypoglycemia that otherwise strongly impair neural performance in most animals. More broadly, they reveal the vertebrate brain has the capacity to serve as its own fuel reserve during the cessation of glucose metabolism, switching seamlessly to locally sourced ketone bodies while maintaining neural activity. This reframes glucose metabolism in the vertebrate brain not as a hard-wired necessity, but as a plastic trait that can in some cases be entirely abandoned. SignificanceThe brain relies on a continuous supply of glucose from the blood to support the large energy demands of neural activity. When glucose delivery is disrupted, neural activity collapses within minutes. Here, we demonstrate that hibernation induces a large capacity for frogs, animals with seemingly normal glucose needs, to operate neural circuits without glucose metabolism, replacing it ketone bodies produced exclusively within the brain. These results reveal that a brain-derived, non-glucose fuel reserve can power neural function in the absence of glucose delivery. These findings reframe neural activitys reliance on continuous glucose metabolism as a plastic trait, rather than a hard-wired constraint.

physiology↗

bioRxiv2026

Frogs uncouple neural activity from oxygen consumption after hibernation

AimAerobic metabolism supplies [~]90% of the ATP for neural activity. In frogs, activity has large aerobic needs typical of an average vertebrate, but surprisingly, can shift to using only glycolysis upon emergence from hibernation. We hypothesized that hibernation triggers a global reduction in the aerobic cost of neural function. MethodsWe simultaneously measured activity of the brainstem respiratory network via motor nerves and tissue oxygen partial pressure (pO2) in vitro from control and hibernated bullfrogs (4 weeks cold submergence; 4{degrees}C). To identify which functions differentially consume O2, we sequentially blocked activity and various cellular processes requiring activity-independent ion regulation and used the resulting tissue pO2 change ({Delta}pO2) as an index of O2 consumed. We further assessed how activity varies as a function of tissue pO2 and how O2 consumption varies across network activity levels. ResultsDespite similar network activity levels, we provide three lines of evidence that hibernation reduces its aerobic requirement. First, hibernators consume less oxygen for baseline activity. Second, network output remains stable from baseline to anoxia, while moderate hypoxia disrupts controls. Finally, accelerating activity does not enhance oxygen consumption as in controls, but aerobic metabolism ultimately increases during seizure-like activity. ConclusionHibernating frogs reduce aerobic needs for sustaining physiological levels of neural activity, revealing how they overcome the challenge of restarting motor circuits on the background of hypoxia during emergence from hibernation. More broadly, vertebrate neural circuits seemingly constrained by aerobic metabolism can exhibit substantial plasticity in the aerobic requirements for function. Practitioner pointsO_LIHibernation in bullfrogs reduces the oxygen consumed by neural activity while maintaining normal network output, demonstrating that the aerobic requirements of brain function are not fixed in the vertebrate brain. C_LIO_LIAfter hibernation, brainstem motor circuits maintain stable function from high levels of O2 to anoxia and do not increase O2 consumption when activity is elevated within the physiological range. C_LIO_LIThese findings reveal that vertebrate neural circuits can enter metabolic states requiring far less aerobic respiration, which may inform strategies for improving metabolic resilience in the brain during conditions of impaired oxygen delivery and other metabolic dysfunction. C_LI

physiology↗

bioRxiv2025

Amygdala GABA Neurons: Gatekeepers of Stress and Reproduction

Stress can disrupt menstrual cycles, cause infertility, and lead to other reproductive disorders. The posterodorsal medial amygdala (MePD) processes stress signals and regulates the gonadotropin-releasing hormone (GnRH) pulse generator through GABAergic inhibitory projections to the hypothalamus. However, how stress is processed in the MePD - especially involving its dense GABA and Urocortin-3 (UCN3) neurons - remains poorly understood. In this study, we combine in vivo GRadient-INdex (GRIN) lens mini-endoscopic calcium imaging (to track neuronal activity), optogenetics, clustering analysis, and computational modeling to investigate the MePD circuitry. Our findings reveal two anti-correlated GABA subpopulations in the MePD that dictate responses to both UCN3 neuron stimulation and restraint stress. Our computational modeling suggests that mutual inhibition between these GABA groups drives the anti-correlated activity and predicts how these interactions shape downstream responses to stimulation of GABA and UCN3 neurons. We test these predictions using optogenetics and confirm that GABA neurons are critical for the transmission of UCN3 signals to regulate luteinizing hormone (LH) pulse frequency. Our study is the first to show how GABA neurons in the amygdala mediate stress effects on reproductive health, uncovering key neural mechanisms linking emotional and reproductive functions.

physiology↗