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...

Forming a long-term memory requires changes in neuronal transcription. What happens, though, as the memory is forgotten? And how does the transcriptional state relate to the maintenance and recall of the long-term memory? To answer these questions, we have been systematically tracing the time course of transcriptional changes evoked by long-term sensitization in the marine mollusk Aplysia californica . Our approach captures transcriptional changes in neurons of known behavioral relevance using a within-subject design, delineating patterns of transcriptional change that are comprehensive and reproducible. We have previously reported that within 1 d of long-term sensitization training, there is a widespread transcriptional response involving robust changes in over 5% of tested transcripts (1,198 of ∼22 k; [Conte et al., 2017][1]). Within 1 week, however, memory strength fades, and nearly all transcriptional changes relapse to baseline ( [Perez et al., 2018][2]). Here we report microarray analysis ( N  = 16) ...

A possible mechanism of temporal lobe epilepsy is insufficient inhibition of hippocampal dentate granule cells. Precipitating injuries that kill interneurons in the dentate gyrus might result in fewer inhibitory synapses with granule cells. To test this hypothesis, previous studies evaluated numbers or densities of interneurons, γ-amino butyric acid (GABA)ergic boutons, and inhibitory synapses in tissue from human patients with temporal lobe epilepsy and rodent models. However, those studies have limitations. Some of those limitations can be addressed by a large animal model. Sea lions ( Zalophus californianus ) can develop temporal lobe epilepsy naturally. Like humans, epileptic sea lions exhibit bilateral or unilateral hippocampal sclerosis (neuron loss) with granule cell vulnerability, but sea lions permit optimal tissue preservation and sampling, and good control subjects. To label interneuron cell bodies and GABAergic synaptic boutons, sea lion hippocampal tissue from both sexes was processed with imm...

The current treatment for drug-resistant epilepsy is surgical intervention, which relies on accurate identification of the seizure onset zone (SOZ) using intracranial electroencephalography (iEEG) data. iEEG analysis with computational epileptogenic zone identification algorithms (CEZIAs) is a promising step toward better SOZ localization and surgical outcomes. A key step in validation and adoption of CEZIAs is to allow for widespread shared development and validation of code and data. To achieve this, we developed an ecosystem of seizure localization methods that includes a straightforward analysis pipeline, standardized data formatting and storage, and completely documented and open-source code. The TableContainer package provides standardized storage of tabular data and serves as a foundational data structure for the ecosystem. Building on this, the Epoch package enables cropping, resampling, and visualization of iEEG data and provides publicly downloadable datasets for reproducibility. The public iEEG ...

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...

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...

Accurate time estimation is essential for optimizing our perception and actions. Previous neuroimaging and transcranial magnetic stimulation (TMS) studies have suggested that the right inferior parietal lobule (IPL) and supplementary motor area (SMA) are involved in time perception. However, it remains inconclusive whether the activity in these regions is crucial for time perception, partly due to the possible spread of TMS effects across anatomically connected brain regions. Such a remote effect is less likely to happen with transcranial static magnetic stimulation (tSMS), as the static magnetic field is expected to modulate the firing threshold of neurons rather than directly triggering an action potential. In this study, we aimed to determine the causal relevance of local activities in the right IPL and the SMA for temporal processing using tSMS. Forty-eight human volunteers (26 males and 22 females) participated in the study. We measured duration discrimination thresholds, along with orientation discri...

Bridging integrator 1 ( BIN1 ) is one of the strongest genetic risk factors for Alzheimer’s disease (AD), yet its function in the brain and role in AD remain unclear. Neuronal BIN1 isoform levels are decreased in AD, and recent data show an important role of BIN1 in inhibitory neurons. Inhibitory neurons are key regulators of cognition and network excitability, with parvalbumin-expressing (PV) neurons as the most abundant subtype. We tested the hypothesis that loss of BIN1 from PV neurons contributes to AD-related cognitive dysfunction and network hyperexcitability. We generated a cell type–specific conditional knock-out mouse line, Bin1- pvKO, and examined mice of both sexes. These mice showed few behavioral differences when assessed with traditional or machine learning–based behavioral tests, with only a slight reduction in exploratory behavior in aged cohorts. Bin1- pvKO mice showed no significant differences in network excitability on measures of induced seizure susceptibility and spiking on cortical e...

Reward prediction errors (RPEs) guide learning by comparing expected and obtained outcomes. In mammals, ventral tegmental area (VTA) activity is closely linked to RPE-like signaling, yet how avian VTA dynamics evolve during reinforcement learning remains less well characterized. Here we recorded VTA spiking in pigeons (two females and one male) performing a cue-guided operant task in which a green cue (cue+) predicted reward contingent on a key peck, whereas a red cue (cue−) was unrewarded. Using a 16-channel microwire array, we analyzed pooled channel-level multiunit activity (MUA) aligned to task events. Across sessions, cue+ trials showed a learning-related redistribution of event-locked modulation: outcome-locked activity was more prominent early in training, while cue-locked modulation became stronger as performance stabilized, consistent with a temporal-difference–like shift of prediction-related signals. Cue− trials were sparse after early learning and showed limited cue-locked modulation in the ava...