AI Article Synopsis
- The study investigates how norepinephrine (NE) influences behavior through cellular mechanisms, focusing on L-type Ca channels (LTCC) in the brain.
- It identifies the role of α-adrenergic receptors (ARs) in increasing LTCC activity in hippocampal neurons via a signaling pathway involving protein kinase C (PKC) and tyrosine kinases Pyk2 and Src.
- The findings suggest that the interaction between LTCC and αAR signaling is crucial for long-term potentiation (LTP) in the hippocampus, which is essential for synaptic strength and memory processes.
Article Abstract
The cellular mechanisms mediating norepinephrine (NE) functions in brain to result in behaviors are unknown. We identified the L-type Ca channel (LTCC) Ca1.2 as a principal target for G-coupled α-adrenergic receptors (ARs). αAR signaling increased LTCC activity in hippocampal neurons. This regulation required protein kinase C (PKC)-mediated activation of the tyrosine kinases Pyk2 and, downstream, Src. Pyk2 and Src were associated with Ca1.2. In model neuroendocrine PC12 cells, stimulation of PKC induced tyrosine phosphorylation of Ca1.2, a modification abrogated by inhibition of Pyk2 and Src. Upregulation of LTCC activity by αAR and formation of a signaling complex with PKC, Pyk2, and Src suggests that Ca1.2 is a central conduit for signaling by NE. Indeed, a form of hippocampal long-term potentiation (LTP) in young mice requires both the LTCC and αAR stimulation. Inhibition of Pyk2 and Src blocked this LTP, indicating that enhancement of Ca1.2 activity via αAR-Pyk2-Src signaling regulates synaptic strength.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10325713 | PMC |
| http://dx.doi.org/10.7554/eLife.79648 | DOI Listing |
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