Biology subjects

Bueschke, N.

Publications and source records attributed to Bueschke, N..

4 recordsLinked to original sources

bioRxiv2026

Activity-dependent homeostatic synaptic plasticity widens the temperature range of synaptic transmission

The framework of homeostatic plasticity posits that neurons regulate cellular properties through feedback homeostasis to maintain activity during changes in the environment. However, when disturbances occur in wild animals they are often caused by environmental variables that induce their own acclimation effects, making it difficult to discern if activity-sensitive feedback plays a role in ecological settings. We addressed this problem using a natural activity perturbation, where frogs hibernate in cold water, leaving brainstem motor circuits that generate breathing inactive for long periods. We show here that motor inactivity, amid complex environmental variables in the hibernation environment, represents a key signal for increasing AMPA-glutamate receptors (AMPARs) on motoneurons. Homeostatic upregulation of AMPARs do not regulate neural activity per se but instead correspond with enhanced evoked transmission selectively at cool temperatures. The results show how homeostatic synaptic plasticity may allow animals to restart motor behavior after chronic inactivity encountered in the natural environment. More broadly, these results introduce the concept of homeostatic plasticity as a mechanism to shape thermal tolerance ranges of neural performance in ecological settings.

neuroscience↗

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↗

bioRxiv2025

Hibernation improves neural performance during energy stress in regions across the central nervous system in the American bullfrog

Neuronal signaling requires high rates of ATP production via the oxidative metabolism of glucose. The American bullfrog is intriguing, as this species has typical brain energy requirements for an average vertebrate but modifies synaptic physiology and metabolism after hibernation to maintain function during hypoxia and ischemia. Given the importance of the respiratory system in restoring metabolic homeostasis during emergence from underwater hibernation, work to date has addressed this response in the brainstem respiratory network. Thus, metabolic plasticity has been interpreted as an adaptation used to restart respiratory motor behavior under hypoxic conditions during the transition from skin breathing to air breathing. It remains unclear whether these improvements are specific to the brainstem regions critical for breathing versus a global response within the central nervous system (CNS). To address this question, we recorded neural activity from the spinal cord, forebrain, and brainstem respiratory network in vitro. As expected, hypoxia disrupted the function of each network in control animals. After hibernation, each network improved its activity in hypoxia compared to controls. These results suggest that plasticity that improves neural function during energy stress following hibernation reflects a global response that may impact many behaviors controlled by the CNS and is not limited to regions involved in metabolic homeostasis.

neuroscience↗

bioRxiv2023

Plasticity in the functional properties of NMDA receptors improves motor circuit performance during severe energy stress

Brain energy stress leads to neuronal hyperexcitability followed by a rapid loss of function and cell death. In contrast, the frog brainstem switches into a state of extreme metabolic resilience that allows them to maintain motor function during hypoxia as they emerge from hibernation. NMDA receptors (NMDARs) are Ca2+-permeable glutamate receptors that contribute to the loss of homeostasis during hypoxia. Therefore, we hypothesized that hibernation leads to plasticity that reduces the role of NMDARs within neural networks to improve function during energy stress. To test this, we assessed a circuit with a large involvement of NMDAR synapses, the brainstem respiratory network of female bullfrogs, Lithobates catesbeianus. Contrary to our expectations, hibernation did not alter the role of NMDARs in generating network output, nor did it affect the amplitude, kinetics, and hypoxia sensitivity of NMDAR currents. Instead, hibernation strongly reduced NMDAR Ca2+ permeability and enhanced desensitization during repetitive stimulation. Under severe hypoxia, the normal NMDAR profile caused network hyperexcitability within minutes, which was mitigated by blocking NMDARs. After hibernation, the modified complement of NMDARs protected against hyperexcitability, as disordered output did not occur for at least one hour in hypoxia. These findings uncover state-dependence in the plasticity of NMDARs, whereby multiple changes to receptor function improve neural performance during energy stress without interfering with its normal role during healthy activity. Significance StatementNeural circuits lose homeostasis during severe energy stress, and NMDA-glutamate receptors play a major role in this response. In contrast, frogs have the remarkable capacity to use plasticity that improves circuit function from minutes to hours during hypoxia, likely as an adaptation to survive emergence from hibernation. We found this occurs, in part, through modification of NMDA receptors that renders them less permeable to Ca2+ and more likely to desensitize during high activity states. These NMDA receptor modifications do not influence normal network function but protect against hyperexcitability caused by hypoxia. This work points to endogenous plasticity mechanisms that improve network function during energy stress without altering circuit function when the brain is well-oxygenated.

neuroscience↗