A functional logic for neurotransmitter corelease in the cholinergic forebrain pathway

Many neuromodulatory brain regions corelease neurotransmitters along with their neuromodulators. Because the function of such corelease is largely unknown, we have examined modulation of the claustrum by the cholinergic system of the basal forebrain. Our findings show that two different claustral output neuron populations respond in opposite ways to acetylcholine (ACh) and GABA coreleased by the cholinergic system. These opposing actions toggle network computations between the two different output neuron pathways. This toggle provides a microcircuit basis for attention-related and learning-related cholinergic computations and affords a previously unappreciated degree of flexibility to the cholinergic system. Thus, our results reveal a functional logic for corelease of ACh and GABA in the claustrum and potentially in other brain areas.