| First Author | Morabito A | Year | 2022 |
| Journal | Cell Rep | Volume | 38 |
| Issue | 8 | Pages | 110415 |
| PubMed ID | 35196488 | Mgi Jnum | J:328740 |
| Mgi Id | MGI:6881884 | Doi | 10.1016/j.celrep.2022.110415 |
| Citation | Morabito A, et al. (2022) Activity-dependent modulation of NMDA receptors by endogenous zinc shapes dendritic function in cortical neurons. Cell Rep 38(8):110415 |
| abstractText | NMDA receptors (NMDARs) have been proposed to control single-neuron computations in vivo. However, whether specific mechanisms regulate the function of such receptors and modulate input-output transformations performed by cortical neurons under in vivo-like conditions is understudied. Here, we report that in layer 2/3 pyramidal neurons (L2/3 PNs), repeated synaptic stimulation results in an activity-dependent decrease in NMDAR function by vesicular zinc. Such a mechanism shifts the threshold for dendritic non-linearities and strongly reduces LTP. Modulation of NMDARs is cell and pathway specific, being present selectively in L2/3-L2/3 connections but absent in inputs originating from L4 neurons. Numerical simulations highlight that activity-dependent modulation of NMDARs influences dendritic computations, endowing L2/3 PN dendrites with the ability to sustain non-linear integrations constant across different regimes of synaptic activity like those found in vivo. Our results unveil vesicular zinc as an important endogenous modulator of dendritic function in cortical PNs. |
