In contrast to our increasingly detailed understanding of how synaptic plasticity provides a cellular substrate for learning and memory, it is less clear how a neuron's voltage-gated ion channels interact with plastic changes in synaptic strength to influence behavior. We find, using generalized and regional knockout mice, that deletion of the HCN1 channel causes profound motor learning and memory deficits in swimming and rotarod tasks. In cerebellar Purkinje cells, which are a key component of the cerebellar circuit for learning of correctly timed movements, HCN1 mediates an inward current that stabilizes the integrative properties of Purkinje cells and ensures that their input-output function is independent of the previous history of their activity. We suggest that this nonsynaptic integrative function of HCN1 is required for accurate decoding of input patterns and thereby enables synaptic plasticity to appropriately influence the performance of motor activity.
SUMMARY
The cerebellum stores associative motor memories essential for properly timed movement; however, the mechanisms by which these memories form and are acted upon remain unclear. To determine how cerebellar activity relates to movement and motor learning, we used optogenetics to manipulate spontaneously firing Purkinje neurons (PNs) in mouse simplex lobe. Using high-speed videography and motion tracking, we found that altering PN activity produced rapid forelimb movement. PN inhibition drove movements time-locked to stimulus onset, whereas PN excitation drove delayed movements time-locked to stimulus offset. Pairing either PN inhibition or excitation with sensory stimuli triggered the formation of robust, associative motor memories; however, PN excitation led to learned movements whose timing more closely matched training intervals. These findings implicate inhibition of PNs as a teaching signal, consistent with a model whereby learning leads first to reductions in PN firing that subsequently instruct circuit changes in the cerebellar nucleus.
Transformation of carbon dioxide to high value‐added chemicals becomes a significant challenge for clean energy studies. Here a stable and conductive covalent organic framework was developed for electrocatalytic carbon dioxide reduction to carbon monoxide in aqueous solution. The cobalt(II) phthalocyanine catalysts are topologically connected via robust phenazine linkage into a two‐dimensional tetragonal framework that is stable under boiling water, acid, or base conditions. The 2D lattice enables full π conjugation along x and y directions as well as π conduction along the z axis across the π columns. With these structural features, the electrocatalytic framework exhibits a faradaic efficiency of 96 %, an exceptional turnover number up to 320 000, and a long‐term turnover frequency of 11 412 hour−1, which is a 32‐fold improvement over molecular catalyst. The combination of catalytic activity, selectivity, efficiency, and durability is desirable for clean energy production.
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