What Is: Biological Plasticity

Image Credit: Scientific Frontline

The Paradigm of the Reactive Genome 

The history of biological thought has long been dominated by a tension between the deterministic rigidity of the genotype and the fluid adaptability of the phenotype. For much of the 20th century, the Modern Synthesis emphasized the primacy of genetic mutation and natural selection, often relegating environmental influence to a mere background filter against which genes were selected. In this view, the organism was a fixed readout of a genetic program, stable and unwavering until a random mutation altered the code. However, a profound paradigm shift has occurred, repositioning the organism not as a static entity but as a dynamic system capable of producing distinct, often dramatically different phenotypes from a single genotype in response to environmental variation. This capacity, known as biological or phenotypic plasticity, is now recognized as a fundamental property of life, permeating every level of biological organization—from the epigenetic modification of chromatin in a stem cell nucleus to the behavioral phase transitions of swarming locusts, and ultimately to the structural rewiring of the mammalian cortex following injury. 

Fueling nerve cell function and plasticity

The picture shows neurons (magenta) born in the adult mouse hippocampus. Nuclei are stained cyan. The extending dendrites are important sites where mechanisms of plasticity and competition for survival take place.
Photo Credit: Courtesy of ©Bergami Lab / University of Cologne

New finding from scientists at the University of Cologne discloses how mitochondria control tissue rejuvenation and synaptic plasticity in the adult mouse brain

Nerve cells (neurons) are amongst the most complex cell types in our body. They achieve this complexity during development by extending ramified branches called dendrites and axons and establishing thousands of synapses to form intricate networks. The production of most neurons is confined to embryonic development, yet few brain regions are exceptionally endowed with neurogenesis throughout adulthood. It is unclear how neurons born in these regions successfully mature and remain competitive to exert their functions within a fully formed organ. However, understanding these processes holds great potential for brain repair approaches during disease.

A team of researchers led by Professor Dr Matteo Bergami at the University of Cologne’s CECAD Cluster of Excellence in Aging Research addressed this question in mouse models, using a combination of imaging, viral tracing and electrophysiological techniques. They found that, as new neurons mature, their mitochondria (the cells’ power houses) along dendrites undergo a boost in fusion dynamics to acquire more elongated shapes. This process is key in sustaining the plasticity of new synapses and refining pre-existing brain circuits in response to complex experiences. The study ‘Enhanced mitochondrial fusion during a critical period of synaptic plasticity in adult-born neurons’ has been published in the journal Neuron.

Ancestral variation guides future environmental adaptations

A sea campion in its natural habitat on the coast.
Photo Credit: Bangor University

The humble sea campion flower can show us how species adapt.

The speed of environmental change is very challenging for wild organisms. When exposed to a new environment individual plants and animals can potentially adjust their biology to better cope with new pressures they are exposed to - this is known as phenotypic plasticity.

Plasticity is likely to be important in the early stages of colonizing new places or when exposed to toxic substances in the environment. New research published in Nature Ecology & Evolution, shows that early plasticity can influence the ability to subsequently evolve genetic adaptations to conquer new habitats.

How the Brain's GABA Brakes Can Act as a Gas Pedal

Image Credit: Scientific Frontline / stock image

Scientific Frontline: Extended "At a Glance" Summary: The Paradoxical Role of GABA

The Core Concept: Gamma-aminobutyric acid (GABA), typically known as the brain's primary inhibitory neurotransmitter that quiets neuronal activity, can under certain conditions act as an excitatory agent that enhances brain signaling.

Key Distinction/Mechanism: While most GABA receptors suppress neural firing, specific interactions with GABA-alpha-5 receptors produce a paradoxical effect. Inhibiting the electrical activity at these specific receptors unexpectedly increases the likelihood that a neuron will draw in calcium ions during its next firing, effectively amplifying calcium-dependent neural plasticity instead of silencing the circuit.

Major Frameworks/Components:

• Gamma-aminobutyric acid (GABA): The major chemical messenger historically categorized strictly as the central nervous system's "brakes."
• GABA-alpha-5 Receptors: One of 19 identified subtypes of GABA-alpha receptors, uniquely responsible for this unexpected excitatory signaling pathway.
• Calcium-Dependent Neural Plasticity: The process by which calcium ion influx strengthens synaptic connections, serving as a fundamental mechanism for learning and memory formation.
• Two-Photon Microscopy: An advanced imaging technique utilized to track the real-time concentration and movement of calcium ions within living mouse neurons.

Neighboring synapses shape learning and memory

A mathematical model reveals how interactions between neighboring contact sites of nerve cells influence learning.
Image Credit: University of Basel, Biozentrum

A researcher at the University of Basel, in collaboration with a colleague in Austria, has developed a new model that provides a holistic view on how our brain manages to learn quickly and forms stable, long-lasting memories. Their study sheds light on the crucial role of interactions among neighboring contact sites of nerve cells for brain plasticity – the brain’s ability to adapt to new experiences.

In 1949, the Canadian psychologist Donald O. Hebb described that connections between neurons become stronger when the neurons are active at the same time and that strengthened connections facilitate signal transmission. The ability of our brain to modify the connections between neurons is fundamental for learning and memory.

 “It has long been assumed that these adaptations occur mostly on a one-on-one basis at specific synapses, the contact sites between two neurons”, explains Dr. Everton Agnes from the Biozentrum, University of Basel. “Interestingly, synapses that undergo changes also affect multiple neighboring synapses.” As these complex synaptic interactions are difficult to investigate experimentally, Agnes and his colleague Prof. Tim Vogels from the Institute of Science and Technology Austria have built a theoretical model to disentangle this phenomenon, also known as co-dependency. Their work has recently been published in Nature Neuroscience.

Algae bio hacks itself in adapting to climate change

Phytoplankton - the foundation of the oceanic food chain.
Photo Credit: NOAA

Clear evidence that marine phytoplankton are much more resilient to future climate change than previously thought is the focus of a study published in Science Advances by an international team of scientists, including University of Hawaiʻi at Mānoa oceanography professor David Karl.

“Knowing how marine algae will respond to global warming and to associated decline of nutrients in upper ocean waters is crucial for understanding the long-term habitability of our planet,” said Karl.

Combining data from the long-term Hawaiʻi Ocean Time-series program at UH Mānoa with new climate model simulations conducted on one of South Korea’s fastest supercomputers, the scientists revealed that a mechanism, known as nutrient uptake plasticity, allows marine algae to adapt and cope with nutrient-poor ocean conditions that are expected to occur over the next decades in response to global warming of the upper ocean.

Immune Signaling in Brain Injuries

An AI-generated illustration, shows how brain injury (the shock wave from the left to the brain) leads to the breaking of neuronal connections/neuronal communication.
Image Credit: Deepak Subramanian, UC Riverside.

Scientific Frontline: Extended "At a Glance" Summary: The TLR4-MMP-9 Axis in Traumatic Brain Injury

The Core Concept: Traumatic brain injuries (TBI) activate the brain's innate immune system—specifically toll-like receptor 4 (TLR4)—which subsequently elevates the enzyme MMP-9 to disrupt neuronal communication, leading to memory loss, seizures, and impaired cognition.

Key Distinction/Mechanism: In a healthy, uninjured brain, TLR4 acts as a homeostatic regulator that balances neural activity. However, following a concussive injury, TLR4 acts upstream to trigger an excessive release of MMP-9, destabilizing the precise balance between excitatory and inhibitory signaling and drastically reducing synaptic plasticity.

Major Frameworks/Components:

• Toll-like Receptor 4 (TLR4): An innate immune receptor that maintains neurological stability in healthy brains but drives network hyperexcitability and "noise" after trauma.
• Matrix Metalloproteinase-9 (MMP-9): An enzyme utilized for remodeling neuronal connections and the extracellular matrix, which alters neuronal communication when excessively upregulated by TLR4.
• Synaptic Plasticity: The fundamental capability of the brain to strengthen and reorganize neural networks, which is significantly impaired by the TLR4-MMP-9 interaction.

A new tool for examining processes in the cerebellum

The Bochum research team: Bianca Preissing, Lennard Rohr, Ida Siveke and Tatjana Surdin (from left)
Photo Credit: © RUB, Marquard

Light can start a signal cascade in the cerebellum. This also illuminates processes that play an important role in cerebellar diseases.

Processes in the cerebellum are involved in various diseases that affect motor learning. A new tool developed by a Bochum working group helps to investigate this better: a light-activated protein that is coupled with part of an exciting receptor. Thanks to this optogenetic tool, light can activate a signaling pathway in the nerve cells of the cerebellum and observe its effects. So, the group around Dr. Ida Siveke from the working group of Prof. Dr. Stefan Herlitze at the Ruhr University Bochum show that the signal path is involved in cerebellar-controlled motor learning. The researchers report in the iSience journal.

What Happens in the Brain While Daydreaming?

The findings provide a clue that daydreams may play a role in brain plasticity
Image Credit: Scientific Frontline 

You are sitting quietly, and suddenly your brain tunes out the world and wanders to something else entirely — perhaps a recent experience, or an old memory. You just had a daydream.

Yet despite the ubiquity of this experience, what is happening in the brain while daydreaming is a question that has largely eluded neuroscientists.

Now, a study in mice, published Dec. 13 in Nature, has brought a team led by researchers at Harvard Medical School one step closer to figuring it out.

The researchers tracked the activity of neurons in the visual cortex of the brains of mice while the animals remained in a quiet waking state. They found that occasionally these neurons fired in a pattern similar to one that occurred when a mouse looked at an actual image, suggesting that the mouse was thinking — or daydreaming — about the image. Moreover, the patterns of activity during a mouse’s first few daydreams of the day predicted how the brain’s response to the image would change over time.

The research provides tantalizing, if preliminary, evidence that daydreams can shape the brain’s future response to what it sees. This causal relationship needs to be confirmed in further research, the team cautioned, but the results offer an intriguing clue that daydreams during quiet waking may play a role in brain plasticity — the brain’s ability to remodel itself in response to new experiences.

Scientists discover anatomical changes in the brains of the newly sighted

MIT neuroscientists discovered anatomical changes that occur in the white matter pathways linking visual-processing areas of the brain in children who have congenital cataracts surgically removed. This image shows the late-visual pathways in the brain.
Illustration Credit: Courtesy of the researchers, edited by MIT News

For many decades, neuroscientists believed there was a “critical period” in which the brain could learn to make sense of visual input, and that this window closed around the age of 6 or 7.

Recent work from MIT Professor Pawan Sinha has shown that the picture is more nuanced than that. In many studies of children in India who had surgery to remove congenital cataracts beyond the age of 7, he has found that older children can learn visual tasks such as recognizing faces, distinguishing objects from a background, and discerning motion.

In a new study, Sinha and his colleagues have now discovered anatomical changes that occur in the brains of these patients after their sight is restored. These changes, seen in the structure and organization of the brain’s white matter, appear to underlie some of the visual improvements that the researchers also observed in these patients.

The findings further support the idea that the window of brain plasticity, for at least some visual tasks, extends much further than previously thought.

The drug gabapentin may boost functional recovery after a stroke

These 3D images of mouse brain vasculature show normal conditions, top, and after an ischemic stroke, which occurs when a blood vessel clot blocks blood flow in the brain.
Credit: Andrea Tedeschi

The drug gabapentin, currently prescribed to control seizures and reduce nerve pain, may enhance recovery of movement after a stroke by helping neurons on the undamaged side of the brain take up the signaling work of lost cells, new research in mice suggests.

The experiments mimicked ischemic stroke in humans, which occurs when a clot blocks blood flow and neurons die in the affected brain region.

Results showed that daily gabapentin treatment for six weeks after a stroke restored fine motor functions in the animals’ upper extremities. Functional recovery also continued after treatment was stopped, the researchers found.

The Ohio State University team previously found that gabapentin blocks the activity of a protein that, when expressed at elevated levels after an injury to the brain or spinal cord, hinders re-growth of axons, the long, slender extensions of nerve cell bodies that transmit messages.

Supernumerary virtual robotic arms can feel like part of our body

VR supernumerary robotic system. In this diagram of the system, the dotted lines represent wireless connections and solid lines represent wired connections.
Credit: 2022 Ken Arai.

Research teams at the University of Tokyo, Keio University and Toyohashi University of Technology in Japan have developed a virtual robotic limb system which can be operated by users’ feet in a virtual environment as extra, or supernumerary, limbs. After training, users reported feeling like the virtual robotic arms had become part of their own body. This study focused on the perceptual changes of the participants, understanding of which can contribute to designing real physical robotic supernumerary limb systems that people can use naturally and freely just like our own bodies.

What would you do with an extra arm, or if like Spider-Man’s nemesis Doctor Octopus, you could have an extra four? Research into extra, or supernumerary, robotic limbs look at how we might adapt, mentally and physically, to having additional limbs added to our bodies.

Doctoral student Ken Arai from the Research Center for Advanced Science and Technology (RCAST) at the University of Tokyo became interested in this research as a way to explore the limits of human “plasticity” — in other words, our brain’s ability to alter and adapt to external and internal changes. One example of plasticity is the way that we can learn to use new tools and sometimes even come to see them as extensions of ourselves, referred to as “tool embodiment,” whether it’s an artist’s paintbrush or hairdresser’s scissors.

Misplaced Neurons Reveal the Brain’s Adaptability

Image Credit: Scientific Frontline / AI generated (Gemini)

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Neurons positioned in the wrong location, known as heterotopias, can successfully integrate into brain circuits and take over the functional role of the normal cerebral cortex, defying the assumption that precise anatomical placement is required for function.
• Methodology: Researchers utilized a mouse model with induced heterotopias and performed functional mapping during a sensory task requiring the distinction of whiskers; they employed targeted deactivation to isolate the contributions of normal versus misplaced neurons.
• Key Data: Mice continued to perform sensory tasks normally when the healthy cortex was deactivated; however, the specific inhibition of the misplaced neuronal clusters resulted in immediate and complete failure of the task.
• Significance: This study fundamentally alters the understanding of brain plasticity, demonstrating that cellular identity and connectivity can override spatial positioning to maintain neurological function.
• Future Application: These findings validate the potential of regenerative therapies, such as neuronal grafts and brain organoids, suggesting they can be effective treatments without needing to perfectly replicate natural brain architecture.
• Branch of Science: Neuroscience (Neurodevelopment and Plasticity).
• Additional Detail: Analysis revealed that these stray neurons formed neural circuits almost identical to those in the healthy cortex, establishing correct connections with both the rest of the brain and the spinal cord.

Astrocytic Lactate: The Hidden Driver of Brain Memory

Professor Pierre Magistretti
Photo Credit: Courtesy of Abdullah University of Science and Technology

Scientific Frontline: Extended "At a Glance" Summary: Astrocyte-Neuron Lactate Signaling

The Core Concept: Astrocytes, the star-shaped glial cells in the brain, actively shuttle lactate to neurons not only as an energy source but as a critical signaling molecule that modulates cellular chemistry and cements learning and memory.

Key Distinction/Mechanism: Deviating from the traditional view that lactate is merely a metabolic byproduct, this mechanism demonstrates that incoming lactate is converted into pyruvate within neurons, generating NADH. This shifts the cellular chemical balance to boost calcium signaling, tightening enzyme activity on NMDA receptors and driving lasting changes in synaptic connection strength.

Major Frameworks/Components:

• Astrocytes: Glial support cells that continuously produce and distribute lactate across neural networks.
• Lactate-to-Pyruvate Conversion: The intracellular metabolic reaction that produces NADH, altering the neuron's chemical equilibrium.
• Calcium Signaling Cascade: A cellular process amplified by the NADH shift, essential for intercellular communication.
• NMDA Receptors: Synaptic proteins governed by neurotransmitters and amplified by astrocyte-derived lactate, directly responsible for driving long-term synaptic plasticity.

What Is: Epigenetics

Scientific Frontline: Extended "At a Glance" Summary: Epigenetics

The Core Concept: Epigenetics refers to the precise molecular mechanisms that dynamically alter gene expression and cellular differentiation without changing the underlying sequence of DNA nucleotides.

Key Distinction/Mechanism: While genetic mutations permanently alter the DNA sequence over successive generations, epigenetic modifications are rapid, highly dynamic, and fundamentally reversible. Operating as cellular "dimmer switches," epigenetic mechanisms manipulate transcription by either directly blocking access to the DNA or structurally remodeling the chromatin into open (euchromatin) or closed (heterochromatin) states in response to environmental factors, stressors, and developmental cues.

Origin/History: Historically, molecular biology was dominated by the unidirectional flow of the central dogma (DNA to RNA to protein) and strict genetic determinism. As the genomic era matured, it became clear that identical somatic cell genomes could not independently account for complex cellular differentiation or real-time environmental adaptability, leading to the discovery of the epigenome as the regulatory layer governing a "Reactive Genome."

What Is: Xenobots

Scientific Frontline: Extended "At a Glance" Summary: What Are Xenobots? Programmable Biological Organisms

The Core Concept: Xenobots are microscopic, programmable biological machines constructed entirely from living cells without any genetic modification. Measuring less than a millimeter, they lack traditional mechanical parts and are entirely organic, biodegradable, and derived primarily from embryonic stem cells of the African clawed frog (Xenopus laevis).

Key Distinction/Mechanism: Unlike inorganic robots engineered with deterministic algorithms, Xenobots are developed using evolutionary algorithms on a supercomputer to optimize biological architectures for specific behavioral goals. They rely on morphological computation and autonomous self-assembly to exhibit ciliary locomotion, molecular memory, swarm intelligence, and kinematic self-replication—a purely mechanical, non-genetic form of reproduction.

Major Frameworks/Components:

• In Silico Morphogenesis: Supercomputer-driven evolutionary algorithms simulate and optimize cellular configurations, applying specific constraints and noise injection to overcome the "sim-to-real gap".
• Kinematic Self-Replication: Utilizing an AI-optimized "Pac-Man" topology to mechanically corral free-floating stem cells into functional offspring, effectively decoupling biological reproduction from genetic division.
• Transcriptomic Plasticity: An inherent cellular adaptation resulting in a "phylostratigraphic shift" toward ancient evolutionary gene expressions when stem cells are isolated from standard embryonic developmental pathways.
• Human-Derived Anthrobots: Motile, multicellular spheroids spontaneously cultivated from adult human tracheal cells that have demonstrated the ability to autonomously bridge and regenerate severed neural tissue in vitro.
• Neurobots: Engineered biobots augmented with neural precursor cells that successfully self-organize into functioning, calcium-firing neural networks capable of autonomous visual gene expression despite lacking eyes.

Proof for theory of visual perception

The research team, led by Prof. Arthur Konnerth (right), Dr. Yang Chen (left), and PhD student Marinus Kloos at the Institute of Neuroscience at the TUM School of Medicine and Health.
Photo Credit: Astrid Eckert / TUM 

Scientific Frontline: Extended "At a Glance" Summary: Theory of Visual Perception (Hubel and Wiesel Model)

The Core Concept: Visual perception is the result of orderly, stepwise computations in the mammalian brain, where specific cortical neurons construct complex visual information from broadly tuned neural inputs. This step-by-step processing allows the brain to selectively respond to distinct visual features, such as edges, contrast, and object orientation.

Key Distinction/Mechanism: Contrary to arguments suggesting that visual feature selectivity originates early in the brain's relay station (the thalamus), evidence proves this selectivity emerges exclusively later within cortical circuits. While thalamic inputs provide robust but non-specific visual signals, subsequent processing within the primary visual cortex (corticocortical connections) is what ultimately creates precise orientation selectivity.

Major Frameworks/Components:

• Hubel and Wiesel Model: The fundamental, stepwise biological framework dictating how the brain processes visual stimuli.
• Thalamocortical vs. Corticocortical Inputs: Distinct neural signaling pathways used to differentiate non-specific thalamic relay signals from highly selective cortical processing.
• Two-Photon Microscopy and Optogenetics: Advanced observational frameworks utilizing high-resolution optical imaging and light-sensitive proteins to "mute" certain neurons, allowing researchers to isolate individual synaptic activity in a living brain.
• Synaptic Plasticity Discrepancy: The isolated framework proving that corticocortical synapses exhibit calcium signals tied to learning and plasticity, whereas thalamocortical synapses do not.

The Quest for the Synthetic Synapse

Spike Timing" difference (Biology vs. Silicon)
Image Credit: Scientific Frontline

The modern AI revolution is built on a paradox: it is incredibly smart, but thermodynamically reckless. A large language model requires megawatts of power to function, whereas the human brain—which allows you to drive a car, debate philosophy, and regulate a heartbeat simultaneously—runs on roughly 20 watts, the equivalent of a dim lightbulb.

To close this gap, science is moving away from the "Von Neumann" architecture (where memory and processing are separate) toward Neuromorphic Computing—chips that mimic the physical structure of the brain. This report analyzes how close we are to building a "synthetic synapse."

Computational Neuroscience: In-Depth Description

Computational neuroscience is the rigorous, interdisciplinary study of brain function in terms of the information processing properties of the nervous system. The primary goal of this field is to understand how electrical and chemical signals are generated, transmitted, and integrated across neurons to produce cognition, perception, and behavior. By constructing theoretical frameworks and employing mathematical models, computational neuroscientists seek to decode the fundamental algorithms of the brain, linking biophysical mechanisms at the cellular level to complex network dynamics.

Ultrasound therapy shows promise as a treatment for Alzheimer’s disease

Professor Jürgen Götz with an ultrasound machine.
Photo Credit: Courtesy of University of Queensland

University of Queensland researchers have found targeting amyloid plaque in the brain is not essential for ultrasound to deliver cognitive improvement in neurodegenerative disorders.

Dr Gerhard Leinenga and Professor Jürgen Götz from UQ’s Queensland Brain Institute (QBI) said the finding challenges the conventional notion in Alzheimer’s disease research that targeting and clearing amyloid plaque is essential to improve cognition.

“Amyloid plaques are clumps of protein that can build up in the brain and block communication between brain cells, leading to memory loss and other symptoms of Alzheimer’s disease,” Dr Leinenga said.

“Previous studies have focused on opening the blood-brain barrier with microbubbles, which activate the cell type in the brain called microglia which clears the amyloid plaque. 

“But we used scanning ultrasound alone on mouse models and observed significant memory enhancement.”