Trends in Neurosciences最新文献

The entorhinal cortex is crucial for declarative memory and spatial cognition. Recent experiments reveal that many entorhinal neurons represent information through ramping activity in which their firing rate changes monotonically between behaviourally relevant boundaries. This Opinion considers the implications of entorhinal ramping dynamics for computations within the hippocampal formation. Localised firing of extensively investigated grid, border, and object cells is suited to categorisation and rapid learning, whereas ramping activity may reflect compressed codes for communication between areas, or entorhinal computations suited to generalisation. Thus, ramping dynamics may be a manifestation of fundamental but largely overlooked mechanisms contributing to memory and spatial cognition, suggesting a need to re-evaluate models of hippocampal-entorhinal function centred exclusively on sparse, localised codes.

The retention and use of long-term memories is crucial for adaptive behavior. While stable memories help organisms anticipate outcomes, they may become maladaptive if not updated to reflect new conditions as the environment changes. Accumulating evidence suggests that forgetting reflects altered activation of engram cells, with memories persisting in a latent state rather than being erased. One explanation for the forgetting of particular memories is active competition between memory engrams for expression in the brain. Behavioral studies reveal that various forms of forgetting stem from this competition. Here we synthesize behavioral research through the lens of engram competition, focusing on its biological substrates and driving factors. We propose a framework to better understand diverse forms of natural forgetting as well as associated pathological conditions.

Noninvasive brain stimulation (NIBS) methods can modulate brain plasticity, the fundamental process by which synaptic connections are strengthened or weakened in response to synaptic activity or external stimuli. This review synthesizes current knowledge regarding how NIBS techniques induce long-lasting synaptic changes resembling long-term potentiation (LTP) and long-term depression (LTD). We place special emphasis on metaplasticity, the process by which prior neural activity influences subsequent plasticity responses. We highlight how various stimulation parameters, brain state, and individual differences shape plasticity outcomes, and emphasize the challenges in achieving consistent therapeutic effects. Additionally, we discuss the potential clinical impact of applying metaplasticity concepts in the treatment of neurological and psychiatric disorders. We outline critical areas for future research and emphasize the importance of developing personalized NIBS protocols that are closely aligned with underlying biological mechanisms to improve therapeutic outcomes.

In common parlance, 'being in touch with your body' is often used positively. However, in a recent study, Banellis, Rebollo, and colleagues show that better stomach-brain synchronisation is actually associated with increased anxiety and depression scores. These findings add an interesting dimension to debates on the role of interoception in mental health.

In a recent study in mice, Faulkner and colleagues revealed that visual cortex representations of learned cues rapidly shifted with a change in the external context. This work highlights the flexible recruitment of distinct neuronal ensembles to maintain behavioral relevance, providing new insights into how the brain balances stability and adaptability in sensory coding.

Numerous studies in humans have demonstrated a strong link between heart and brain function at different timescales. We conceptualize this functional coupling using different dimensions of brain-body states, formed through the integration of the central and peripheral nervous systems (PNS and CNS, respectively). Using concepts from dynamical systems theory, we discuss how patterns of brain-body dimensions traverse a state space. Attractors signify stable configurations, which we categorize as micro-, meso-, or macro-states according to their duration and reversibility. These reflect different underlying mechanisms, such as neural interactions, hormonal signaling, and structural plasticity. Longer-lasting states restrict the space of possible (shorter-term) brain-body states underlying the mutual dependence of cardiovascular and brain function over the lifespan and in the development of diseases such as hypertension and depression. These considerations, which can be further generalized to include immunological and metabolic dimensions of brain-body states, have broad conceptual and clinical implications.

In long-lived mammals, including humans, brain cell homeostasis is critical for maintaining brain function throughout life. Most neurons are generated during development and must maintain their cellular identity and plasticity to preserve brain function. Although extensive studies indicate the importance of recycling and regenerating cellular molecules to maintain cellular homeostasis, recent evidence has shown that some proteins and RNAs do not turn over for months and even years. We propose that these long-lived cellular molecules may be the basis for maintaining brain function in the long term, but also a potential convergent target of brain aging. We highlight key discoveries and challenges, and propose potential directions to unravel the mystery of brain cell longevity.

Recent studies report reduced dementia risk following shingles vaccination, suggesting that varicella-zoster virus (VZV) latency contributes to neuroimmune vulnerability. We propose that subclinical VZV reactivation acts as a renewable peripheral immune stressor, amplifying microglial priming in aging brains. Shingles vaccination may suppress this viral reservoir, reducing cumulative inflammatory tone. In this opinion article we contrast this mechanism with trained immunity and highlight how pathogen-specific and systemic effects may converge. Finally, we discuss the role of innate phagocytosis and resolution, suggesting that impaired clearance, rather than activation alone, sustains neuroinflammatory risk. Vaccination may thus modulate innate responsiveness and preserve neuroimmune balance in later life.

The brain's ability to adapt and support learning relies on experience-dependent synaptic plasticity, where connections between neurons are strengthened or weakened in response to activity. Recent research in mammalian systems reveals microRNAs (miRNAs) as crucial regulators of this process, offering a new perspective on how neurons achieve timely, localized control of protein synthesis. Neuronal activity influences every stage of the miRNA life cycle, from transcription to transport, maturation, and decay. Transcriptional regulation enables neuron-wide structural adaptations, while synapse-specific transport and maturation ensure localized protein synthesis. Though incompletely understood, activity-regulated miRNA decay allows for reversible modulation of gene expression. These discoveries highlight miRNAs as an essential layer of regulation, bridging neuronal activity with molecular changes that support learning and memory.

In a recent study, Lish and colleagues used a fully human-based, induced pluripotent stem cell (iPSC)-derived triculture model of neurons, astrocytes, and microglia to delineate non-cell autonomous contributions to familial Alzheimer's disease (AD). This approach offers a versatile platform to explore early disease mechanisms, dissect cell-cell interactions, and support the development of targeted therapeutic or biomarker strategies.