| First Author | Fisahn A | Year | 2011 |
| Journal | Eur J Neurosci | Volume | 34 |
| Issue | 7 | Pages | 1121-30 |
| PubMed ID | 21966978 | Mgi Jnum | J:178006 |
| Mgi Id | MGI:5297001 | Doi | 10.1111/j.1460-9568.2011.07834.x |
| Citation | Fisahn A, et al. (2011) Acoustic startle hypersensitivity in Mceph mice and its effect on hippocampal excitability. Eur J Neurosci 34(7):1121-30 |
| abstractText | Current therapies and research for epilepsy concentrate mainly on controlling the disease, but not on prevention of its development and progression. This is partly due to the under-appreciated heterogeneity of the different epileptic syndromes, and a lack of knowledge about the underlying mechanisms of hypersensitivity and hypersynchrony in epilepsy development and spread. In this study we investigate mechanisms underlying the increased susceptibility to acoustic startle in a mouse model homozygous for the spontaneous megencephaly (mceph) mutation, which results in a lack of the functional potassium channel Kv1.1. Mceph mice are hypersensitive to acoustic startle, a response that is not seen in the wild-type (WT) littermates. After acoustic startle, a strong activation of astrocytes, as indicated by glial fibrillary acidic protein, occurred in the inferior colliculus and hippocampus. Both the hypersensitivity of acoustic startle as well as activation of astrocytes could be maintained at WT levels by pre-treating the Mceph mice with the anti-epileptic drug valproate. Furthermore, we utilized the Mceph mouse model to investigate whether acoustic startle-induced hypersensitivity has negative consequences for synchronous neuronal activity in other, non-auditory, systems and networks in the brain, such as the hippocampus. Our findings show that acoustic startle-induced hypersensitivity primes hippocampal networks by increasing their excitability, which results in increased strength of rhythmic network activity. Our results provide novel insights into the mechanisms that underlie the spread of hypersensitivity and hypersynchrony across functionally different parts of the brain. |
