Progress in Neurobiology最新文献

Prosocial behaviour, as a facet of social behaviour across species, entails voluntary actions that benefit others, including helping and comforting behaviours. To explain how external sensory information is integrated to generate motivation and ultimately govern prosocial action, we organize its emergence into three interacting components: a social orientation process centered on the superior colliculus (SC), which selects and evaluates social cues and calibrates attention and arousal; a framework formed by the medial prefrontal cortex (mPFC) and the anterior cingulate cortex (ACC), which transforms perceived distress into internal representations, forming empathic memory that guides subsequent behavior; and neuromodulatory systems (e.g., oxytocin and dopamine) together with projections linking the insular cortex (IC), thalamus, and ventral tegmental area (VTA), that compose social motivation, assign value to prosocial acts and promote helping. Evidence across these processes suggests alignment and potential generalisation in autism spectrum disorder (ASD), which is marked by atypical attention to social signals and diminished responsiveness to social reward. We define prosocial neural network mapping as the characterisation of interregional projections and their neuromodulatory regulation to explain how social information is organised and transformed, offering new insights into circuit-level pathology in ASD and helping identify therapeutic targets aimed at restoring social salience and enhancing social motivation.

Increasing attention has been directed towards the perturbation of glutamate (Glu) and γ-aminobutyric acid (GABA) homeostasis during the pathogenesis of Alzheimer's disease (AD). The prevailing disequilibrium, stemming from hyperactivation of the glutamatergic system, culminates in progressive neuronal impairment and cognitive deterioration. This study aimed to elucidate the contributory role of the ATP-binding cassette transporter A7 (ABCA7), identified as the second most critical genetic determinant in AD, in glutamatergic-associated neurotoxicity. This endeavor sought to advance molecular comprehension of neurological disorders where Glu-GABA neurotransmission represents a pivotal pharmacotherapeutic target. Utilizing multi-omics approaches, we rigorously analyzed four distinct mouse models, both with and without APPtg and ABCA7 expression, to simulate varied pathological and ABCA7-deficient states. Our results revealed amyloid-beta (Aβ) deposition as a catalyst for surging glutamatergic transmission. Notably, ABCA7 ablation exacerbated glutamatergic-induced neurotoxicity, attributed to diminished enzymatic activity related to neurotransmitter degradation and amplified expression levels of specific neurotransmitter transport proteins and receptor subunits, notably NMDA, AMPA, and GABA_A. These findings furnish the first comprehensive description elucidating ABCA7's amplification of neurotoxic effects through modulation of Glu-GABA neurotransmission systems in neurodegenerative contexts, primarily mediated by lipid interaction. The evidence underscores ABCA7's imperative role in shaping future pharmacological strategies aimed at counteracting neurodegeneration precipitated by Glu-mediated neurotoxicity. This research advances the frontier for therapeutic exploration to ameliorate the deleterious neural consequences characteristic of neurodegenerative pathologies.

Aging is associated with increased vulnerability to a wide variety of diseases and conditions, including traumatic brain injury (TBI). While advanced age is a known predictor of poorer outcomes following TBI, the molecular mechanisms underlying this susceptibility haven't been completely characterized. This review discusses some of the primary pathways and physiological changes that are affected by aging and how they influence the post-TBI recovery in both experimental and clinical settings. Some of the age-related alterations implicated in geriatric TBI include loss of white matter, compromised blood-brain-barrier integrity, aggravated oxidative stress, mitochondrial dysfunction, higher cell death and synapse loss, increased and more prolonged neuroinflammation, compromised neural repair mechanisms, dysregulated proteasomal degradation leading to misfolded protein aggregation, and systemic changes such as peripheral organ dysfunction. This review further focuses on how the underlying molecular mechanisms involved in these changes influence long-term functional and behavioral outcomes after TBI. Lastly, some of the current and potential therapeutic interventions for geriatric TBI have also been discussed.

Reaching and grasping in primates require coordinated control of several parameters, such as grip type, wrist orientation, spatial position, and hand laterality. The anterior intraparietal (AIP) and rostral ventral premotor (F5) areas are key hubs in this process. This study used electrophysiological data to investigate how these parameters are co-represented in AIP and F5. The results indicate that neurons predominantly show mixed selectivity with stable temporal organization related to movement and pre-movement phases. This uncategorizable mixture of selectivity allows flexible decoding. Despite condition-dependent shifts, selectivity preferences were largely preserved across task conditions. Notably, object-related factors (orientation and position) remained more stable during grip type changes in AIP, whereas grip type was more stable in F5, suggesting a functional hierarchical organization of context-dependent coding in both areas. Together, despite the continuous range of mixed selectivity at the single-neuron level, neural ensembles exhibit a stable organization on the temporal and functional scales, enabling flexible readouts.

Hippocampal mossy fiber boutons are unique, highly plastic synapses within the hippocampal circuitry. Despite mossy fiber bouton's potential role in learning and memory processes, the precise underlying mechanisms leading to their strengthened synaptic connections are still not fully understood. Here, we provide an overview of the structural changes occurring during long-term potentiation of large presynaptic terminals formed by mossy fiber onto CA3 pyramidal cells. Such changes encompass (1) adaptations in the number, shape and size of the bouton; (2) changes in availability of synaptic vesicles as well as the number and occupancy of release sites within single boutons; and (3) nano-architectural changes in the molecular composition and spatial arrangements within active zones. We describe these changes and possible implications for mossy fiber function. Furthermore, we discuss open questions, current methodology, and possible future directions.