The neuroscience of planning has long been analogized to search algorithms in artificial intelligence (AI), which simulate future actions to guide immediate choices. We argue that advances in both neuroscience and AI suggest that planning is better understood to encompass a broader class of computations where mental simulation supports learning, often well before a decision is needed. We review three neurocomputational mechanisms that illustrate this shift. First, hippocampal replay resembles search but also often occurs prospectively or offline, likely training downstream circuits rather than directly guiding choice. Second, temporally abstract representations, such as grid cells, can enable planning without iterative search. Third, metalearning may shape how prefrontal dynamics implement task-specific planning strategies, echoing how AI systems learn to adapt across contexts. This view recasts the brain's planning machinery as a family of learning processes that leverage simulations to build representations and strategies, with forward search as one special case.
The thermosensory system enables animals to detect and respond to changes in external temperature and is therefore essential for survival, yet remains significantly understudied. This review summarizes current knowledge of its organization in adult Drosophila melanogaster: from peripheral cellular receptors and molecular detection mechanisms to the brain circuits that process thermal information, beginning with second-order thermosensory projection neurons and their targets. The powerful tools available in Drosophila have driven significant advances, revealing the organization of this system at the periphery, the reach of thermosensory pathways within the brain, and the range of behaviors directly influenced by external temperature. These findings also open new avenues to examine how the thermosensory system has been reshaped under changing thermal conditions as Drosophila species evolved to colonize diverse thermal environments.
Category learning-the ability to group individual objects, experiences, and concepts into higher-level abstract representations-is fundamental to fast, flexible decision-making and generalization of knowledge to novel situations. While categories and concepts have traditionally been studied in humans and nonhuman primates, this review puts the focus on the lesser-known domain of rodent category learning. Within the context of human and nonhuman primate work, we highlight the behavioral capabilities and limitations of rodents in categorization tasks, and discuss the neural circuits identified so far. Finally, we outline a roadmap for uncovering the systems and synaptic mechanisms that support the representation of learned categories in the mammalian brain.
Posttraumatic stress disorder (PTSD) is unique in its requirement of an external stressor for the development of disease, leading to dysregulated mood, intrusive memories, and avoidance symptoms. Over the past decade, insights from human neuroimaging, mechanistic neural circuitry studies in animal models, and genomic work have revolutionized our understanding of this psychiatric illness, with emerging data from large-scale PTSD genome-wide association studies providing novel insights into the mechanism of PTSD. Despite these advances, therapeutic interventions remain limited, and psychotherapy remains the first-line treatment over pharmacological interventions. Here, we review the basic epidemiology of PTSD with an overview of common types of trauma, neurocircuits and molecular mechanisms contributing to fear learning, genomics studies, and current and emerging treatments. Although PTSD remains highly prevalent, recent advances and emerging identification of neural circuits and putative molecular targets offer an exciting opportunity to advance the treatment of this debilitating condition.
During pregnancy, the maternal body undergoes profound, coordinated physiological adaptations to support the developing fetus, including major shifts in immune regulation and dramatic changes in the vascular system. Accompanying these peripheral adaptations, recent longitudinal studies in humans point to significant remodeling of the nervous system, occurring in lockstep with increases in gonadal hormone production. To understand the neural adaptations tied to pregnancy and the postpartum period, a holistic approach is essential-one that accounts for changes across multiple peripheral systems. In this review, we consider the impact of the endocrine, cardiovascular, microbiome, and immune systems on the maternal brain. By adopting this integrative approach, we aim to better understand the biological pathways that shape the maternal brain during normative pregnancies and those marked by adverse events.
Foraging, defined as the search for food to sustain one's energetic needs, is a fundamental behavior performed by almost all animals to survive in their environment. Foraging involves a variety of physiological processes, including metabolic and cognitive computations. In this review, we provide a brief historical overview of foraging and foraging theory, highlight recent insights into the neural mechanisms of foraging, and contextualize them within the broader neuroscience literature. We present an integrative approach to foraging that combines neural mechanisms of foraging with ecological, behavioral, and physiological mechanisms.
The head serves as a multifunctional nexus through which animals engage with the external world-gathering sensory input, breathing, feeding, and producing communication signals. These diverse functions must be executed with constrained anatomical resources, often requiring the same oropharyngeal structures to participate in multiple behaviors. Such overlap demands precise coordination to prevent catastrophic errors such as choking or aspiration, while ensuring that breathing and eating proceed without conflict. Operating largely outside conscious awareness, brainstem circuits choreograph these actions by controlling multiple muscle groups with remarkable precision and adaptability. Interactions between different rhythm-generating circuits can weave distinct actions-like whisking with sniffing or licking and chewing-into integrated behaviors that serve survival needs. Recent advances in circuit dissection, targeted manipulations, and large-scale electrophysiological recordings are uncovering neurons and functional connections that support precise, coordinated, yet flexible, orofacial actions. These studies provide new insights into how brainstem circuitry achieves precise and effective control over one of biology's most demanding motor challenges.
The brain is a highly integrated organ, capable of dynamically adjusting its internal states through interactions with the ever-changing environment. This moment-to-moment control underlies the process from sensory perception to behavioral output, reflecting the essence of biological intelligence. However, the broad and ambiguous concept of "brain state" poses challenges for unifying research findings and deciphering the neural logic underlying sensory-induced state changes. Here, we focus on arousal-an essential and quantifiable dimension of brain state-which we further subdivide into general arousal and behavior-relevant specific arousal. Building on recent advances, we examine how salient sensory stimuli rapidly drive state transitions to promote adaptive behavior. We further highlight conserved features shared across subcortical sensory systems and provide an abstract framework for how distinct systems couple sensory input to arousal levels. This perspective clarifies mechanisms underlying behavioral flexibility and sensory consciousness, offering a unified framework for interpreting diverse findings in the field.
Visual systems evolved to extract behaviorally relevant information while animals move through and interact with their world. Such ecological vision differs fundamentally from standard laboratory paradigms in many key aspects, making this a much harder problem for the brain to solve, and for the neuroscientist to study. However, emerging technologies and experimental approaches have enabled investigation of visual computations under these ecological conditions. These approaches are particularly powerful in the mouse, combining well-developed genetic tools, high-throughput recordings, and quantifiable ethological tasks. Here we review computations that are engaged in ecological contexts, including active sensing, motion processing, scene analysis, distance estimation, and spatial perception. We delineate experimental approaches that engage these computations and synthesize current understanding of their neural implementations based on mouse research. These studies reveal how ecological vision engages distinct processing strategies and novel neural circuitry, while highlighting the vast territory that remains unexplored in understanding real-world visual computation.
Stressors, including those occurring in early development, predict an increased risk for psychopathology. The challenge is that of defining causal pathways that connect stressful conditions to specific health outcomes and then leveraging this knowledge toward treatments. This review focuses on glucocorticoids (GCs), the end products of stressor-induced hypothalamic-pituitary-adrenal axis activity, and reviews evidence, including recent multiomics analyses, regarding their role in mental health. We outline the challenges in translating this knowledge into effective treatments and recent evidence for the potential of gene network analyses to identify molecular pathways linking stress to psychopathology. A detailed examination of GC activity through the glucocorticoid receptor is presented as an example of the complexities involved in achieving this research objective and paths to novel interventions through gene network analyses.
Sex hormones are a primary source for biological variation throughout the animal kingdom, from morphological characteristics to elaborate courtship displays. These steroids, such as estrogens and androgens, are indispensable for the development and function of the nervous tissues that mediate sex differences in reproduction, metabolism, and social behavior. Crucially, the cognate receptors for sex hormones are transcription factors that bind DNA to regulate expression of nearby genes. Although there has been substantial recent progress in dissecting the neural circuitry that regulates sex-differential behaviors, there is a dearth of understanding regarding how sex hormones act on this circuitry to modulate behavior. Here, we focus on the transcriptional actions of sex hormone receptors and the functions of their target genes, particularly voltage-gated ion channels. We put forth a framework in which sex hormone receptor modulation of gene expression affects cell activity states across interconnected brain regions, leading to emergent social behaviors.
Somatosensory ganglia are often cast as passive relays, yet growing evidence shows the dorsal root ganglion (DRG) is a specialized sensory-immune organ. In the DRG, perineuronal and perivascular units act as sentinels that detect danger and calibrate immune tone. A permeable, macrophage-guarded blood-DRG barrier admits systemic cues, while neuron-glia microdomains set sensory gain and help restore homeostasis. Throughout the organ, neurons, glia, and vascular-stromal cells share immune receptors, enabling coordinated responses to infection, inflammation, and autoimmunity. In turn, neuronal signals reshape vascular tone and leukocyte trafficking, whereas immune mediators can promote recovery or drive pathology. Single-cell and spatial atlases reveal regenerative programs and zonation that organize these circuits. Together, these insights reframe the DRG as an integrator linking immune state to sensory encoding and pain. Preserving DRG structure-by fortifying barriers, stabilizing glial buffering, and steering macrophages toward resolution-could blunt maladaptive neuroimmune interactions and enable durable pain relief without compromising host defense.
In the adult mammalian brain, thalamocortical input supports key cortical functions by conveying ascending information from subcortical sensory and motor centers and linking different cortical areas. Studies in the 1980s revealed that these afferent projections are also critical for building the mature neocortex, which is composed of six layers and dozens of anatomically and functionally distinct areas. Recent studies have begun to provide a comprehensive view of cortical development, encompassing early regionalization of immature cortical tissue, distinct behaviors of various progenitor cell types, fate specification of neurons forming the six layers, and morphological and functional maturation of each neuronal type leading to the formation of distinct areas. Many of these processes are now known to be influenced by thalamocortical input. This review highlights the historical contexts in which the roles of the thalamus were uncovered, drawing on evidence from a wide range of organisms, cortical regions, and cell types.
Social touch is a critical component of our daily lives, shaping our interactions with friends and loved ones. Reduced social touch, especially during early life, can have detrimental effects on health and well-being. A mechanistic understanding of the neural circuits for social touch is still underway, despite its centrality. To achieve a comprehensive understanding of social touch, a cellular and molecular emphasis must be placed on signaling and connectivity among neurons of the skin, spinal cord, and brain. Here, I review research on the molecules, cells, and circuits of the social touch network, highlighting insights from humans, nonhuman primates, and rodents. I conclude by exploring some of the exciting avenues for future research.
The neuron is no longer viewed as a simple point-like integrator but as a sophisticated computational device whose power resides in its dendritic arbor. This review charts the paradigm shift driven by this new perspective. We synthesize recent in vivo findings from behaving animals, where active dendritic processes, from local nonlinear spikes to compartment-specific plasticity, are revealed to be fundamental for intelligence, including perception, action, and memory across key brain regions. We then explore how these biological mechanisms are formalized in theoretical and circuit models that explain complex neural computations at the network level. Finally, we highlight the potential of these findings for artificial intelligence, arguing that dendritic computation offers a compelling source of inspiration for future learning algorithms and hardware systems. This review solidifies dendritic computation as a cornerstone of modern neuroscience, linking cellular mechanisms to the principles of intelligent systems.
Psychedelics are a broad category of compounds that induce altered states of consciousness. These drugs have shown remarkable promise for the treatment of debilitating disorders ranging from posttraumatic stress disorder to depression and addiction. Although early studies focused on linking binding targets of psychedelics to their therapeutic effects, these pharmacological and biochemical explanations fail to account for the diversity, durability, and context dependence of psychedelics' clinical and acute subjective effects. More recently, neurobiological explanations offer fresh insights and demonstrate that a unifying property of psychedelics is that these compounds reopen critical periods, induce metaplasticity, and reorganize the extracellular matrix. Here we review this evidence and argue that the neurobiological and therapeutic effects of psychedelics challenge the biochemical imbalance model that has dominated translational neuroscience since the 1950s and favor instead a learning model that better accounts for psychedelics' unique therapeutic profile.
Path integration (PI), the ability to keep track of position and orientation from self-motion, is a sensitive cognitive marker of Alzheimer's disease. While entorhinal grid cells are central to PI, we focus here on the broader functional circuit supporting PI and the impact of Alzheimer's disease within it. This circuit includes orientation from head direction cells, landmark-based error correction, and signals encoding current or intended movement direction, which we suggest may rely on theta-modulated directional cells and theta sweeps in grid and place cell firing. The early vulnerability of PI, particularly angular PI, may reflect multiple sources: pathology in the anterodorsal thalamus degrading head direction coding; disrupted theta rhythmicity and thus theta-modulated directional signals, potentially reflecting cholinergic dysfunction; and retrosplenial landmark-resetting failures allowing angular drift. We advocate for further cross-species investigation of PI tasks with electrophysiological measures to fully identify the underlying circuit mechanisms and their impairment in Alzheimer's disease.
Predictive coding proposes that the brain constructs internal models of the world to continuously predict sensory input and uses resulting errors to refine these models. Over the past several decades, neurophysiological studies have reported activity patterns consistent with this view. However, varied definitions and inconsistent empirical evidence have raised questions about its validity and explanatory scope. In this review, we provide a historical overview of the predictive processing framework and evaluate its empirical support, particularly focusing on sensory prediction error signals. We argue that clarifying what information these signals represent is crucial, as they may appear similar in their responses yet reflect fundamentally different underlying computations. We then revisit predictive coding, highlighting alternative accounts of how sensory prediction error signals encode information. Finally, we outline key directions for future work, aiming to provide a constructive roadmap for the next phase of predictive processing research and to advance our understanding of the neuronal algorithms underlying perception and cognition.
Physiological needs, such as the need for food, water, and sleep, are fulfilled through homeostatic processes by which brain circuits monitor changes in internal states and trigger goal-directed behaviors, such as eating, drinking, and sleeping, that are aimed to restore physiological balance. Increasing evidence, in humans and animals alike, points to social interaction as yet another fundamental need regulated by homeostatic processes. In this review, we highlight recent efforts to identify neuronal circuits and cell populations underlying social drive, social satiety, and overall social homeostasis, and we compare newly identified neural and molecular mechanisms governing social and physiological needs. We summarize shared and distinct features across distinct needs at the levels of behavioral expression, neuronal circuit function, molecular mechanisms, and sensory modulation. Findings across distinct homeostatic systems offer broad insights into the organizational principles of homeostatic regulation and lay ground for new avenues of research on the brain response to social isolation.
