Biology subjects

Pollak, Y. E.

Publications and source records attributed to Pollak, Y. E..

3 recordsLinked to original sources

bioRxiv2026

Cortex-wide representational drift of different layers

Representational drift, the gradual evolution of neural population codes over days, has been widely documented at the level of single neurons. However, whether drift is organized across larger cortical populations and spatial scales remains unclear. Here, we examined cortex-wide population dynamics under tightly controlled sensory input and behavior. Using widefield calcium imaging, we longitudinally recorded excitatory activity in Layers 2/3 (L2/3) or Layer 5 (L5) across 25 cortical areas while mice performed a whisker-based texture discrimination task. Sensory-evoked activity was tracked over five consecutive days during stable task performance. Population activity patterns reorganized over days, across the cortex, in both layers. This reorganization followed distinct laminar motifs: notably L5 responses exhibited a widespread, monotonic decrease in activity across most cortical areas, whereas L2/3 responses showed spatially localized and heterogeneous changes that were strongest during the sensory period. These laminar differences extended beyond the stimulus period, with L5 exhibiting more prolonged temporal engagement than L2/3. Together, these findings indicate that representational drift can unfold as a process that is coordinated across cortex with distinct laminar profiles. Thus, drift may reflect a structured feature of cortex-wide circuit dynamics.

neuroscience↗

bioRxiv2025

Cortex-wide laminar dynamics diverge during learning

Learning to link sensory information to motor actions involves dynamic coordination across cortical layers and regions. However, the involvement of a particular layer in learning, especially from a cortex-wide perspective, is relatively unknown. Using wide-field calcium imaging in mice as they learn a whisker-based go/no-go task, we tracked activity in layers 2/3 or 5 (L2/3 or L5) across 25 cortical areas. A surprising initial effect of learning was that activity in L5 but not in L2/3 was globally suppressed at auditory cue onset. As the texture comes into touch, we found that L2/3 displayed learning-related enhancements in higher order association areas rostrolateral (RL) and secondary somatosensory (S2), whereas L5 in these areas oppositely decreased. During texture touch, the barrel cortex (BC) displayed similar learning-related enhancement in both layers. As sensory information is transformed into a motor action, there was a frontal/posterior divergence that emerges after learning, in which L5 was enhanced in the frontal cortex and L2/3 was suppressed in the posterior cortex. In general, learning related correlations were often stronger between distant cortical layers than within the same column, suggesting that learning drives laminar interactions that transcend traditional columnar organization. Together, these results reveal that learning orchestrates a dynamic interplay of activity across space, time and cortical layers. Our findings emphasize the critical role of laminar architecture in shaping cortical plasticity and support the view that layer-specific circuits are fundamental to sensorimotor learning.

neuroscience↗

bioRxiv2021

Chronic kidney disease alters Pin1 phosphorylation and parathyroid hormone mRNA binding proteins leading to secondary hyperparathyroidism

Parathyroid hormone (PTH) regulates calcium metabolism and bone strength. Chronic kidney disease leads to secondary hyperparathyroidism (SHP) which increases morbidity and mortality. In experimental SHP, the increased PTH gene expression is due to enhanced PTH mRNA stability, mediated by changes in its interaction with stabilizing AUF1 and destabilizing KSRP. Pin1 isomerizes target proteins and leads to KSRP dephosphorylation. In SHP, Pin1 isomerase activity is decreased and phosphorylated KSRP fails to bind PTH mRNA, resulting in high PTH mRNA stability and levels. However, the up- and down-stream mechanisms by which kidney failure stimulates the parathyroid remain elusive. We now reveal a pathway where kidney failure induces parathyroid Pin1 phosphorylation, linking Pin1, KSRP and PTH mRNA stability as key players for the high PTH expression in SHP. We identified by mass-spectrometry, changes in rat parathyroid proteome and phosphoproteome profiles induced by impaired renal function, including KSRP phosphorylation at Pin1 target sites. Furthermore, both acute and chronic kidney failure led to parathyroid-specific Pin1 Ser16 and Ser71 phosphorylation, which disrupts Pin1 activity. Accordingly, pharmacologic Pin1 inhibition, that mimics the decreased Pin1 activity in SHP, increased PTH expression ex-vivo in parathyroid organ cultures and in transfected cells, through the PTH mRNA protein-interacting element and KSRP phosphorylation at potential Pin1-binding motifs. Therefore, kidney failure leads to loss of parathyroid Pin1 activity by inducing Pin1 phosphorylation. This predisposes parathyroids to increase PTH production through impaired PTH mRNA decay that is dependent on KSRP phosphorylation. Pin1 and KSRP phosphorylation and the Pin1-KSRP-PTH mRNA axis thus drive SHP.

molecular biology↗