| First Author | Snyder MA | Year | 2016 |
| Journal | J Neurochem | Volume | 138 |
| Issue | 5 | Pages | 700-9 |
| PubMed ID | 27260635 | Mgi Jnum | J:235229 |
| Mgi Id | MGI:5795789 | Doi | 10.1111/jnc.13695 |
| Citation | Snyder MA, et al. (2016) Sigma receptor type 1 knockout mice show a mild deficit in plasticity but no significant change in synaptic transmission in the CA1 region of the hippocampus. J Neurochem 138(5):700-9 |
| abstractText | The sigma-1 receptor (sigma-1R) is a chaperone protein located at the endoplasmic reticulum (ER) mitochondrial interface with roles in neuroprotection and cognition. Increasing evidence suggests that loss of sigma-1R function could contribute to neurological disease states making it a target for therapeutic intervention. Our objective was to elucidate the consequences to synaptic transmission and plasticity when sigma-1R is absent. We utilized a knockout mouse in which the gene encoding for sigma-1R was deleted (sigma-1R-KO mouse). Using whole-cell patch-clamp recordings from CA1 pyramidal neurons in the hippocampus, we examined neuronal excitability and glutamatergic synaptic function. Surprisingly, we detected no significant change in action potential firing and basic cellular characteristics. Furthermore, we found no significant change to pre-synaptic function as indicated by a similar paired-pulse ratio and miniature excitatory post-synaptic current frequency in sigma-1R-KO compared to wild-type (WT) mice. Similarly, the glutamate gated AMPA receptor and NMDA receptors were unaffected with no significant difference in AMPA/NMDA ratio or decay kinetics in sigma-1R-KO compared to WT mice. We further examined long-term potentiation in extracellular field recordings in CA1 stratum radiatum following Schaffer collateral stimulation. Interestingly, we found a small but significant reduction in the magnitude of long-term potentiation in mutant compared to WT mice. The results of this investigation suggest that basic cellular physiology is unaffected by sigma-1R loss, however the neuronal network is partially compromised. The sigma-1 receptor (sigma-1R) is a chaperone protein with roles in neuroprotection and cognition. We determined the consequences to synaptic transmission and plasticity when sigma-1R was absent. Utilizing the sigma-1R knockout mouse and electrophysiological recordings, we found no change in neuronal excitability and glutamatergic synaptic function. However, we found a significant reduction in long-term potentiation. |
