Despite the substantial contribution of disruptions in GABAergic inhibitory neurotransmission to the etiology of psychiatric, neurodevelopmental, and neurodegenerative disorders, surprisingly few drugs targeting the GABAergic system are currently available, partly due to insufficient understanding of circuit-specific GABAergic synapse biology. In addition to GABA receptors, GABAergic synapses contain an elaborate organizational protein machinery that regulates the properties of synaptic transmission. Until recently, this machinery remained largely unexplored, but key methodological advances have now led to the identification of a wealth of new GABAergic organizer proteins. Notably, many of these proteins appear to function only at specific subsets of GABAergic synapses, creating a diversity of organizer complexes that may serve as circuit-specific targets for pharmacotherapies. The present review aims to summarize the methodological developments that underlie this newfound knowledge and provide a current overview of synapse-specific GABAergic organizer complexes, as well as outlining future avenues and challenges in translating this knowledge into clinical applications.

Somatostatin-expressing (SST) neurons are a major class of electrophysiologically and morphologically distinct inhibitory cells in the mammalian neocortex. Transcriptomic data suggest that this class can be divided into multiple subtypes that are correlated with morpho-electric properties. At the same time, availability of transgenic tools to identify and record from SST neurons in awake, behaving mice has stimulated insights about their response properties and computational function. Neocortical SST neurons are regulated by sleep and arousal, attention, and novelty detection, and show marked response plasticity during learning. Recent studies suggest that subtype-specific analysis of SST neurons may be critical for understanding their complex roles in cortical function. In this review, we discuss and synthesize recent advances in understanding the diversity, circuit integration, and functional properties of this important group of GABAergic neurons.

Rhythmic neural activity is considered essential for adaptively modulating responses in the visual system. In this opinion article we posit that visual brain rhythms also serve a key function in the representation and communication of visual contents. Collating a set of recent studies that used multivariate decoding methods on rhythmic brain signals, we highlight such rhythmic content representations in visual perception, imagery, and prediction. We argue that characterizing representations across frequency bands allows researchers to elegantly disentangle content transfer in feedforward and feedback directions. We further propose that alpha dynamics are central to content-specific feedback propagation in the visual system. We conclude that considering rhythmic content codes is pivotal for understanding information coding in vision and beyond.

How do you know you have heard right? Metacognition, the ability to assess and monitor one's own cognitive state, is key to understanding human communication in complex environments. However, the foundational role of metacognition in hearing and communication is only beginning to be explored, and the neuroscience behind it is an emerging field: how does confidence express in neural dynamics of the listening brain? What is known about auditory metaperceptual alterations as a hallmark phenomenon in psychosis, dementia, or hearing loss? Building on Bayesian ideas of auditory perception and auditory neuroscience, 'meta-listening' offers a framework for more comprehensive research into how metacognition in humans and non-humans shapes the listening brain.

Chemotherapy treatment can significantly increase the survival of patients with cancer, but it also causes collateral damage in the body that can lead to treatment dose reductions and can reduce patient quality of life. One understudied side effect of chemotherapy is circadian disruption, which is associated with lasting biological and behavioral toxicities. Mechanisms of how chemotherapy alters circadian rhythms remain largely unknown, although leveraging rodent models may provide insights into causes and consequences of this disruption. Here, we review physiological, molecular, and behavioral evidence of central and peripheral circadian disruption in various rodent models of chemotherapy and discuss possible mechanisms driving these circadian disruptions. Overall, restoring circadian rhythms following treatment-induced disruptions may be a novel target by which to improve the health and quality of life of survivors.

Despite extensive functional mapping studies using rodent functional magnetic resonance imaging (fMRI), interpreting the fMRI signals in relation to their neuronal origins remains challenging due to the hemodynamic nature of the response. Ultra high-resolution rodent fMRI, beyond merely enhancing spatial specificity, has revealed vessel-specific hemodynamic responses, highlighting the distinct contributions of intracortical arterioles and venules to fMRI signals. This 'single-vessel' fMRI approach shifts the paradigm of rodent fMRI, enabling its integration with other neuroimaging modalities to investigate neuro-glio-vascular (NGV) signaling underlying a variety of brain dynamics. Here, we review the emerging trend of combining multimodal fMRI with opto/chemogenetic neuromodulation and genetically encoded biosensors for cellular and circuit-specific recording, offering unprecedented opportunities for cross-scale brain dynamic mapping in rodent models.

The precise organization of the complex set of synaptic proteins at the nanometer scale is crucial for synaptic transmission. At the heart of this nanoscale architecture lies the nanocolumn. This aligns presynaptic neurotransmitter release with a high local density of postsynaptic receptor channels, thereby optimizing synaptic strength. Although synapses exhibit diverse protein compositions and nanoscale organizations, the role of structural diversity in the notable differences observed in synaptic physiology remains poorly understood. In this review we examine the current literature on the molecular mechanisms underlying the formation and maintenance of nanocolumns, as well as their role in modulating various aspects of synaptic transmission. We also discuss how the reorganization of nanocolumns contributes to functional dynamics in both synaptic plasticity and pathology.

Memory consolidation requires rapid energy supply to neurons. In a recent study, Francés et al. revealed the signal by which a neuron commands glia to limit fatty acid synthesis in favor of metabolite export during memory formation in Drosophila melanogaster. This mechanism coordinates just-in-time glial energy delivery in response to dynamic neuronal needs.

The evolution of vertebrates from protochordate ancestors marked the beginning of the gradual transition to predatory lifestyles. Enabled by the acquisition of multipotent neural crest and cranial placode cell populations, vertebrates developed an elaborate peripheral nervous system, equipped with paired sense organs, which aided in adaptive behaviors and ultimately, successful colonization of diverse environmental niches. Underpinning the enduring success of vertebrates is the highly adaptable nature of the peripheral nervous system, which is enabled by the exceptional malleability of the neural crest and placode developmental programs. Here, we explore the embryonic origins of the vertebrate senses from the neural crest and cranial placodes and discuss the evolutionary trajectory of the senses in the context of adaptation to novel environments.

Neuronal hyperexcitability in the cortex and hippocampus represents an early event in Alzheimer's disease (AD). In a recent study, Blankenship and colleagues reported that in a mouse of AD, ventral tegmental area (VTA) dopamine neurons are also hyperexcitable, and this hyperexcitability is due to casein kinase 2 (CK2)-dependent SK channel dysfunction, adding new insights into the underlying mechanisms of aberrant neuronal properties in AD.

Neurodegenerative disorders represent a leading cause of disability among the elderly population, and Parkinson's disease (PD) is the second most prevalent. Emerging evidence suggests a frequent co-occurrence of circadian disruption and PD. However, the nature of this relationship remains unclear: is circadian disruption a cause, consequence, or a parallel feature of the disease that shares the same root cause? This review seeks to address this question by highlighting and discussing clinical evidence and findings from experiments using vertebrate and invertebrate animal models. While research on causality is still in its early stages, the available data suggest reciprocal interactions between PD progression and circadian disruption.

Despite accounting for only ~0.001% of all neurons in the human brain, midbrain dopaminergic neurons control numerous behaviors and are associated with many neuropsychiatric disorders that affect our physical and mental health. Dopaminergic neurons form various anatomically and functionally segregated pathways. Having such defined dopaminergic pathways is key to controlling varied sets of brain functions; therefore, segregated dopaminergic pathways must be properly and uniquely formed during development. How are these segregated pathways established? The three key developmental stages that dopaminergic neurons go through are cell migration, axon guidance, and synapse formation. In each stage, dopaminergic neurons and their processes receive unique molecular cues to guide the formation of specific dopaminergic pathways. Here, we outline the molecular mechanisms underlying the establishment of segregated dopaminergic pathways during each developmental stage in the mouse brain, focusing on the formation of the three major dopaminergic pathways: the nigrostriatal, mesolimbic, and mesocortical pathways. We propose that multiple stage-specific molecular gradients cooperate to establish functionally segregated dopaminergic circuits.

A recent study by Kaneko and colleagues provides evidence that developing cranial motor neurons in larval zebrafish refine their input specificity over time, using an activity-dependent mechanism that may depend, in part, on adaptive dendrite extension. These findings illuminate the mechanism by which spatially overlapping motor pools are recruited into distinct motor circuits.

Developing effective treatments for amyotrophic lateral sclerosis (ALS) has been hindered by both the complexity of the disease and decentralized research efforts. By fostering collaboration, standardization, and inclusivity, the Accelerating Medicines Partnership® (AMP®) ALS initiative aims to lay the foundation for future discoveries in ALS biomarkers and treatments.

The dorsal striatum is instrumental in regulating motor control and goal-directed behaviors. The classical description of the two output pathways of the dorsal striatum highlights their antagonistic control over actions. However, recent experimental evidence implicates both pathways and their coordinated activities during actions. In this review, we examine the different models proposed for striatal encoding of actions during self-paced behaviors and how they can account for evidence harvested during goal-directed behaviors. We also discuss how the activation of striatal ensembles can be reshaped and reorganized to support the formation of instrumental learning and behavioral flexibility. Future work integrating these considerations may resolve controversies regarding the control of actions by striatal networks.

The lateral thalamus (LT) receives input from primary sensory nuclei and responds to multimodal stimuli. The LT is also involved in regulating innate and social behaviors through its projections to cortical and limbic networks. However, the importance of multisensory processing within the LT in modulating behavioral output has not been explicitly addressed. Here, we discuss recent findings primarily from rodent studies that extend the classical view of the LT as a passive relay, by underscoring its involvement in associating multimodal features and encoding the salience, valence, and social relevance of sensory signals. We propose that the primary function of the LT is to integrate sensory and non-sensory aspects of multisensory input to gate naturalistic behaviors.

Across studied vertebrates, the medial amygdala (MeA) is a central hub for relaying sensory information with social and/or survival relevance to downstream nuclei such as the bed nucleus of stria terminalis (BNST) and the hypothalamus. MeA-driven behaviors, such as mating, aggression, parenting, and predator avoidance are processed by different molecularly defined inhibitory and excitatory neuronal output populations. Work over the past two decades has deciphered how diverse MeA neurons arise from embryonic development, revealing contributions from multiple telencephalic and diencephalic progenitor domains. Here, we first provide a brief overview of current findings regarding the role of the MeA in social behaviors, followed by a deeper dive into current knowledge of how this complex structure is specified during development. We outline a conceptual model of MeA formation that has emerged based on these findings. We further postulate how embryonic developmental programming of the MeA may inform later emergence of stereotypical circuitry governing hardwired behaviors.

Recent studies in non-human primates do not find pronounced signals related to the animal's own body movements in the responses of neurons in the visual cortex. This is notable because such pronounced signals have been widely observed in the visual cortex of mice. Here, we discuss factors that may contribute to the differences observed between species, such as state, slow neural drift, eccentricity, and changes in retinal input. The interpretation of movement-related signals in the visual cortex also exemplifies the challenge of identifying the sources of correlated variables. Dissecting these sources is central for understanding the functional roles of movement-related signals. We suggest a functional classification of the possible sources, aimed at facilitating cross-species comparative approaches to studying the neural mechanisms of vision during natural behavior.

In a recent study, Haas, Bravo, and colleagues integrated optogenetic stimulation with simultaneous functional in vivo positron emission tomography (PET)/magnetic resonance imaging (MRI) measurements in rats. By activating the nigrostriatal pathway in the substantia nigra pars compacta (SNc), they observed concurrent metabolic and hemodynamic fluctuations associated with the dopaminergic pathway in living animals at the whole-brain level.

In pancreatic cancer, significant alterations occur in the local nervous system, including axonogenesis, neural remodeling, perineural invasion, and perineural neuritis. Pancreatic cancer can impact the central nervous system (CNS) through cancer cell-intrinsic factors or systemic factors, particularly in the context of cancer cachexia. These peripheral and central neuropathic changes exert substantial influence on cancer initiation and progression. Moreover, chemotherapy-induced neuropathy is common in pancreatic cancer, causing peripheral nerve damage and cognitive dysfunction. Targeting the crosstalk between pancreatic cancer and the nervous system, either peripherally or centrally, holds promise in cancer treatment, pain relief, and improved quality of life. Here, we summarize recent findings on the molecular mechanisms behind these neuropathic changes in pancreatic cancer and discuss potential intervention strategies.