“The subiculum, considered to be the output structure of
the hippocampus, modulates information flow from the hippocampus to various cortical and sub-cortical areas such as the nucleus accumbens, lateral septal region, thalamus, nucleus gelatinosus, medial nucleus and mammillary nuclei. Tonic inhibitory current plays an important role in neuronal physiology and pathophysiology by modulating the electrophysiological properties of neurons. While the alterations of various electrical properties due to tonic inhibition have been studied in neurons from different regions, its influence on intrinsic subthreshold resonance in pyramidal excitatory neurons expressing hyperpolarization-activated cyclic nucleotide-gated (HCN) channels is not known. Using pharmacological agents, we show the involvement of α5βγ GABAA receptors in the picrotoxin-sensitive tonic current in subicular pyramidal neurons. We further
BGB324 ic50 investigated the contribution of tonic conductance in regulating subthreshold electrophysiological properties using current clamp and dynamic clamp experiments. We demonstrate that tonic GABAergic inhibition can actively modulate find more subthreshold properties, including resonance due to HCN channels, which can potentially alter the response dynamics of subicular pyramidal neurons in an oscillating neuronal network. “
“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 STK38 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.