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Physiological and pathological plasticity in identified hippocampal inhibitory interneurons

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Hippocampal inhibitory neuronal network consists of specialized GAB Aergic interneuron types with distinct anatomical properties. Certain interneurons express activity-induced lasting plasticity by and large similar to long-term potentiation (LTP) and –depression (LTD) in principal cells. However, plasticity in GAB Aergic inhibitory network is more diverse than in principal cells. Four different long-term plasticity forms are elicited by specific activity patterns in the hippocampal CA1 area. Anatomical analyses demonstrate that plasticity is specific to interneuron type.

Degenerative brain diseases may also be associated with cell type-specific changes in GAB Aergic inhibitory interneuron population. We have looked into properties of hippocampal circuits in mice which over-express a common schizophrenia risk gene neuregulin-1 (NRG1). NRG1 and its receptor ErbB4 play a role in the formation and maturation of inhibitory GAB Aergic circuits. NRG1 transgenic mice show impaired working memory. In addition recordings in hippocampal slices reveal distorted gamma (20-80 Hz) oscillation and altered GAB Aergic inhibition. We have used optical stimulation of light-gated channel channelrhodopsin-2 selectively expressed in interneuron axons to uncover the mechanisms underlying changed inhibition.

We suggest that changes restricting to distinct interneuron types have different impacts in hippocampal network function.

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