| First Author | Freund RK | Year | 2016 |
| Journal | Neurosci Lett | Volume | 627 |
| Pages | 1-6 | PubMed ID | 27233215 |
| Mgi Jnum | J:328392 | Mgi Id | MGI:6878428 |
| Doi | 10.1016/j.neulet.2016.05.043 | Citation | Freund RK, et al. (2016) Genetic knockout of the alpha7 nicotinic acetylcholine receptor gene alters hippocampal long-term potentiation in a background strain-dependent manner. Neurosci Lett 627:1-6 |
| abstractText | Reduced alpha7 nicotinic acetylcholine receptor (nAChR) function is linked to impaired hippocampal-dependent sensory processing and learning and memory in schizophrenia. While knockout of the Chrna7 gene encoding the alpha7nAChR on a C57/Bl6 background results in changes in cognitive measures, prior studies found little impact on hippocampal synaptic plasticity in these mice. However, schizophrenia is a multi-genic disorder where complex interactions between specific genetic mutations and overall genetic background may play a prominent role in determining phenotypic penetrance. Thus, we compared the consequences of knocking out the alpha7nAChR on synaptic plasticity in C57/Bl6 and C3H mice, which differ in their basal alpha7nAChR expression levels. Homozygous alpha7 deletion in C3H mice, which normally express higher alpha7nAChR levels, resulted in impaired long-term potentiation (LTP) at hippocampal CA1 synapses, while C3H alpha7 heterozygous mice maintained robust LTP. In contrast, homozygous alpha7 deletion in C57 mice, which normally express lower alpha7nAChR levels, did not alter LTP, as had been previously reported for this strain. Thus, the threshold of Chrna7 expression required for LTP may be different in the two strains. Measurements of auditory gating, a hippocampal-dependent behavioral paradigm used to identify schizophrenia-associated sensory processing deficits, was abnormal in C3H alpha7 knockout mice confirming that auditory gating also requires alpha7nAChR expression. Our studies highlight the importance of genetic background on the regulation of synaptic plasticity and could be relevant for understanding genetic and cognitive heterogeneity in human studies of alpha7nAChR dysfunction in mental disorders. |
