Brain structure & function
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The basal forebrain (BF) is an important regulator of hippocampal and cortical activity. In Alzheimer's disease (AD), there is a significant loss and dysfunction of cholinergic neurons within the BF, and also a hypertrophy of fibers containing the neuropeptide galanin. Understanding how galanin interacts with BF circuitry is critical in determining what role galanin overexpression plays in the progression of AD. ⋯ Galanin disrupts this cholinergic-GABAergic circuit by blocking the cholinergic-induced increase in GABA release. These data suggest that galanin works in the BF to reduce inhibitory input onto cholinergic neurons and to prevent cholinergic-induced increase in inhibitory tone. This disinhibition of cholinergic neurons could serve as a compensatory mechanism to counteract the loss of cholinergic signaling that occurs during the progression of AD.