Chemogenetic Deconstruction of Basal forebrain control of wakefulness and cortical rhythms--Nature Communications

Wakefulness, along with fast cortical rhythms and associated cognition, depend on the basal forebrain (BF). BF cholinergic cell loss in dementia and the sedative effect of anti-cholinergic drugs have long implicated these neurons as important for cognition and wakefulness. The BF also contains intermingled inhibitory GABAergic and excitatory glutamatergic cell groups whose exact neurobiological roles are unclear. Here we show that genetically targeted chemogenetic activation of BF cholinergic or glutamatergic neurons in behaving mice produced significant effects on state consolidation and/or the electroencephalogram but had no effect on total wake. Similar activation of BF GABAergic neurons produced sustained wakefulness and high-frequency cortical rhythms, whereas chemogenetic inhibition increased sleep. Our findings reveal a major contribution of BF GABAergic neurons to wakefulness and the fast cortical rhythms associated with cognition. These findings may be clinically applicable to manipulations aimed at increasing forebrain activation in dementia and the minimally conscious state.

Comments

  1. UnknownNovember 6, 2015 at 2:23 AM

    Hi maybe its not the right spot to ask the question, but has anyone experience or knows of a way to activate DREADD only in the peripheral nervous system? Like pegylated CNO that doesn't pass the blood brain barrier?

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    Replies
    1. zendudestNovember 8, 2015 at 6:10 AM

      Interesting idea and would probably work if it was given a bit of thought

      Delete

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