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Sigma receptor type 1 knockout mice show a mild deficit in plasticity but no significant change in synaptic transmission in the CA 1 region of the hippocampus
Author(s) -
Snyder Melissa A.,
McCann Kieran,
Lalande Maryline J.,
Thivierge JeanPhilipe,
Bergeron Richard
Publication year - 2016
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13695
Subject(s) - ampa receptor , long term potentiation , neurotransmission , nmda receptor , excitatory postsynaptic potential , neuroscience , glutamatergic , biology , synaptic plasticity , schaffer collateral , neuroprotection , glutamate receptor , long term depression , sigma 1 receptor , hippocampal formation , microbiology and biotechnology , receptor , inhibitory postsynaptic potential , biochemistry , agonist
The sigma‐1 receptor (σ‐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 σ‐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 σ‐1R is absent. We utilized a knockout mouse in which the gene encoding for σ‐1R was deleted (σ‐1R‐ KO mouse). Using whole‐cell patch‐clamp recordings from CA 1 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 σ‐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 σ‐1R‐ KO compared to WT mice. We further examined long‐term potentiation in extracellular field recordings in CA 1 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 σ‐1R loss, however the neuronal network is partially compromised.The sigma‐1 receptor (σ‐1R) is a chaperone protein with roles in neuroprotection and cognition. We determined the consequences to synaptic transmission and plasticity when σ‐1R was absent. Utilizing the σ‐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.