2023/11/08 by Hovy Ho‐Wai Wong, Alanna J. Watt, P. Jesper Sjöström · 1 voice
Biochemistry, Genetics and Molecular Biology · Neuroscience · #Lipid Membrane Structure and Behavior #Neuroscience and Neuropharmacology Research #RNA regulation and disease
paper · pdf · doi:10.1016/j.neuron.2023.10.011
openalex publication_date 2023/11/08 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
Neurotransmission in the brain is unreliable, suggesting that high-frequency spike bursts rather than individual spikes carry the neural code. For instance, cortical pyramidal neurons rely on bursts in memory formation. Protein synthesis is another key factor in long-term synaptic plasticity and learning but is widely considered unnecessary for synaptic transmission. Here, however, we show that burst neurotransmission at synapses between neocortical layer 5 pyramidal cells depends on axonal protein synthesis linked to presynaptic NMDA receptors and mTOR. We localized protein synthesis to axons with laser axotomy and puromycylation live imaging. We whole-cell recorded connected neurons to reveal how translation sustained readily releasable vesicle pool size and replenishment rate. We live imaged axons and found sparsely docked RNA granules, suggesting synapse-specific regulation. In agreement, translation boosted neurotransmission onto excitatory but not inhibitory basket or Martinotti cells. Local axonal mRNA translation is thus a hitherto unappreciated principle for sustaining burst coding at specific synapse types.