eNeuro current issue

CRF Receptor Type 1 Modulates the Nigrostriatal Dopamine Projection and Facilitates Cognitive Flexibility after Acute and Chronic Stress

Becchi, S., Burton, C. L., Tsoukalas, M., Bowring, J., Balleine, B. W., Mor, D. — 2026-03-05T09:30:12-08:00

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 and SNpc and CRFR1 expression in the SNpc in the left hemisphere were associated with resilience to AS in naive rats, but with an impairment in RRS + AS rats. Blocking CRFR1 in the left SNpc impaired cognitive flexibility following AS in naive rats but restored it following AS in RRS rats. Blocking CRFR1 in the SNpc increased DA availability in the DMS but decreased it in the DLS. The study suggests opposite facilitation in DA availability in the medial and lateral DS by CRFR1 in the SNpc and a left-to-right transition in dopaminergic nigrostriatal projection activity as a protective mechanism following RRS.

Functional-Structural Coupling: Brain Reorganization in Presbycusis Is Related to Cognitive Impairment

2026-03-02T09:30:14-08:00

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 the increase in PTA and SRT. The FSR reduction in the FFG, precuneus, and medial superior frontal gyrus were also significantly associated with the increase in PTA and SRT. Moreover, it was also significantly correlated with lower scores on the Montreal Cognitive Assessment (MoCA) and the Auditory Verbal Learning Test (AVLT), as well as the prolonged time in the Trail Making Test (TMT-A). Presbycusis involves coupled structural atrophy and functional decline in auditory and higher-order cognitive regions. Crucially, reduced FSR correlates with both worsening hearing thresholds and cognitive impairment. This highlights FSR as a key neurobiological link between hearing loss and cognitive decline. This research provides a novel basis for early screening and dynamic monitoring of presbycusis-related cognitive impairment.

Dynamic Encoding of Reward Prediction Error Signals in the Pigeon Ventral Tegmental Area during Reinforcement Learning

Shang, Z., Zhang, J., Li, M., Li, S., Wang, Y., Yang, L. — 2026-03-04T09:30:13-08:00

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 available dataset. Together, these results provide initial evidence that pigeon VTA pooled MUA exhibits learning-related dynamics consistent with RPE-like processing and support cross-species comparisons of dopaminergic learning signals.