Sparse labeling techniques are essential for morphological analysis of the central nervous system. Various sophisticated strategies have been developed, but conventional methods, such as Golgi–Cox staining and biocytin injection, remain widely used. Recent advances in adeno-associated virus (AAV) technology have enabled sparse neuronal labeling in rodents, either through postnatal AAV injection or by coinjecting a dilute Cre recombinase-expressing driver with a Cre-dependent amplifier. However, postnatal AAV injection requires prior preparation, and Cre-dependent systems are incompatible with Cre-expressing or floxed genetic backgrounds. Here, we present a Cre-orthogonal AAV–based sparse labeling method that utilizes Supernova technology in male and female mice. We employed Flpe recombinase to achieve Cre-independent labeling. A retro-orbital injection of PHP.eB AAVs failed to label neurons, whereas local injection enabled the bright and sparse labeling of multiple neuronal types, including cerebellar neur...

A central approach in neuroscience is to analyze neural representations as a means to understand a system's function, through the use of methods like principal component analysis, regression, and representational similarity analysis. These analyses often rest on a tacit “linking assumption”: that the features explaining the most variance in neural activity are the most important for the system's computation. Here, we challenge this assumption. We review recent work in machine learning demonstrating “representation biases”—the fact that learned representations can be biased toward certain features over others. For example, learned representations heavily overrepresent simple (linear) features while representing complex (nonlinear) features much more weakly, even when both are equally critical for the system's computations. We review the origins of these biases in learning dynamics and patterns of computation. We then discuss their consequences for neuroscience. We show that if a subset of features dominates...

Presbycusis, a prevalent neurodegenerative disorder, is characterized by declining speech recognition and has been associated with cognitive impairments across multiple domains. However, the underlying neurobiological mechanisms between presbycusis and cognitive impairments remain unclear. We assessed pure-tone audiometry thresholds (PTA), speech recognition thresholds (SRT), and cognitive abilities in individuals with presbycusis (24 males and 31 females) and healthy controls (23 males and 32 females). Using magnetic resonance imaging, we calculated the amplitude of low-frequency fluctuations (ALFF) to characterize function and gray matter volume (GMV) to characterize structure. Based on ALFF and GMV, we calculated functional-structural ratio (FSR) to measure the functional-structural coupling. Significant correlations between GMV atrophy and ALFF changed in the putamen, fusiform gyrus, precuneus, and medial superior frontal gyrus in presbycusis group, and these changes were significantly associated with ...

Repeated restraint stress (RRS) in rats impairs cognitive flexibility, particularly when faced with additional mild acute stress (AS). We tested the hypothesis that this impairment is associated with altered dopaminergic activity in the dorsal striatum (DS) driven by corticotropin-releasing-factor receptor type 1 (CRFR1) in the substantia nigra pars compacta (SNpc). Sixty-two male rats received RRS or handling for 14 d, before training on a two-action, two-outcome instrumental conditioning task. Initial learning was assessed using an outcome devaluation test. Cognitive flexibility was assessed by reversing the outcome identities and a second outcome devaluation test, with half the rats in each group receiving AS before reversal training. Dopamine and metabolites were quantified in the DS, and CRFR1 mRNA was quantified in the SNpc. In Experiment 2, SNpc CRFR1 was pharmacologically blocked unilaterally before AS and reversal training in 32 male and 32 female rats. Increased dopaminergic activity in the DS an...

Charcot–Marie–Tooth disease (CMT) is an inherited peripheral neuropathy characterized by sensory dysfunction and muscle weakness, manifesting in the most distal limbs first and progressing more proximal. Over a hundred genes are currently linked to CMT with enrichment for activities in myelination, axon transport, and protein synthesis. Mutations in tRNA synthetases cause dominantly inherited forms of CMT, and animal models with CMT-linked mutations in these enzymes display defects in neuronal protein synthesis. Rescuing protein synthesis in CMT-mutant neurons could offer exciting therapeutic options beyond symptom management. To address this need, we expressed CMT-linked variants of tyrosyl-tRNA synthetase (YARS–CMT) in primary mouse sensory neurons derived from both male and female embryos and evaluated impacts on protein synthesis and cell viability. YARS–CMT expression reduced protein synthesis in these neurons prior to the onset of caspase-dependent axon degeneration and cell death. To determine how Y...

Science education is traditionally framed as a driver of scientific literacy and economic growth. However, emerging evidence suggests that it may also function as a contributor to public health by shaping brain health across the lifespan. In this invited commentary, I synthesize findings from human and animal studies to examine how enriched, inquiry-based educational experiences intersect with neural processes underlying cognitive development, stress regulation, executive function, and social-emotional well-being. This synthesis is guided by the principle of cognitive compassion, which emphasizes the design of learning environments that support both cognitive and emotional needs. Research on neuroplasticity, stress biology, and motivation indicates that learning contexts characterized by curiosity, emotional safety, and active engagement are associated with adaptive neural function and long-term cognitive resilience. Drawing on empirical literature and illustrative translational observations from education...

Consumption varies across the stages (metestrus, diestrus, proestrus, estrus) of a rat's estrous cycle, changing in ways that might be expected to reflect, in part, a direct impact of hormones on taste palatability. Evidence regarding this hypothesis has been mixed, however, and critical within-subject experiments comparing consumption of multiple tastes with distinct valences across all estrous phases have been few. Here, we assayed female rats' licking of palatable (saccharin, sucrose, NaCl) and aversive (quinine-HCl, citric acid) tastes in brief-access trials, while tracking their estrous cycles through vaginal cytology. We observed sucrose palatability to be high at metestrus, the same phase at which the palatability of the aversive citric acid was low. These patterns were consistent across tastes of similar palatability, despite vast differences between the substances' receptor mechanisms and central impacts. Together, these results reveal a general (i.e., independent of particular tastant identity) m...

Harmonicity is a property of complex sounds such as vocalizations or music, but it remains unclear how harmonicity is processed in the auditory cortex (ACtx). Subregions of ACtx are thought to process harmonic stimuli differently. Selective responses to sound features in ACtx emerge hierarchically from primary ACtx (A1) L4 and secondary ACtx (A2) layer (L)2/3, which is believed to be the most responsive to harmonic sounds. Since harmonic stacks can range from 2 to >10 components, being more similar to naturalistic vocalizations, harmonic sensitivity might also arise hierarchically across layers and areas. We studied responses to harmonic stacks of 2–10 frequencies across A1 L4, A1 L2/3, and A2 L2/3 in adult male and female mice using in vivo two-photon microscopy. We found harmonic-sensitive neurons (HNs) responding only to harmonic stacks but not to individual frequencies in all areas at similar proportions. HNs showed highly nonlinear spectral integration of harmonic frequencies that decreased as the har...

Rapid advancements in artificial intelligence (AI) have enabled text-to-speech (TTS) systems to produce voices increasingly indistinguishable from humans, posing significant societal risks, particularly through potential misuse in fraud and deception. To address this concern, this study combined behavioral assessments and neural measures using electroencephalography (EEG) to examine whether short-term perceptual training enhances people's ability to distinguish AI-generated from human speech. Thirty participants (of either sex) listened to sentences produced by human speakers and corresponding AI-generated clones, judging each sentence as either human or AI-generated before and after a brief (∼12 min) training session, during which voices were explicitly labeled as “human” or “AI.” Behaviorally, participants showed consistently poor discrimination before and after training, with only minimal improvement. However, neural analyses revealed substantial training-induced changes. Specifically, temporal response...

Rodent hippocampal power spectra comprise periodic and aperiodic components. The periodic components (brain rhythms) contain information about the behavioral or cognitive state of the animal. The aperiodic components are rarely studied, and their functionality is not well understood, though they have shown to be correlated with animal's age or the excitation–inhibition ratio of the brain region. To study these components in the mouse hippocampus, we modified the existing open-source FOOOF toolbox, which was originally optimized for EEG data. First, using simulated data, we show that our modifications decrease the error in assessment of the low frequency periodic components from 3 to 0.1%. Second, using tetrode electrophysiological signals from adult males, we compare the aperiodic activity within mice hippocampal subregions, CA1 and dentate gyrus (DG). Our optimization of FOOOF improved the aperiodic assessment errors by ∼50% and were critical in making the first assessment of the aperiodic components in t...