Synaptic acetylcholine induces sharp wave ripples in the basolateral amygdala through nicotinic receptors
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While the basolateral amygdala (BLA) is critical in the consolidation of emotional memories, mechanisms underlying memory consolidation in this region are not well understood. In the hippocampus, memory consolidation depends upon network signatures termed sharp wave ripples (SWR). These SWRs largely occur during states of awake rest or slow wave sleep and are inversely correlated with cholinergic tone. While high frequency cholinergic stimulation can inhibit SWRs through muscarinic acetylcholine receptors, it is unclear how nicotinic acetylcholine receptors or different cholinergic firing patterns may influence SWR generation. SWRs are also present in BLA in vivo . Interestingly, the BLA receives extremely dense cholinergic inputs, yet the relationship between acetylcholine (ACh) and BLA SWRs is unexplored. Here, using brain slice electrophysiology in male and female mice, we show that brief stimulation of ACh inputs to BLA reliably induces SWRs that resemble those that occur in the BLA in vivo . Repeated ACh-SWRs are induced with single pulse stimulation at low, but not higher frequencies. ACh-SWRs are driven by nicotinic receptors which recruit different classes of local interneurons and trigger glutamate release from external inputs. In total, our findings establish a previously undefined mechanism for SWR induction in the brain. They also challenge the previous notion of neuromodulators as purely modulatory agents gating these events but instead reveal these systems can directly instruct SWR induction with temporal precision. Further, these results intriguingly suggest a new role for the nicotinic system in emotional memory consolidation.
Significance Statement
Sharp wave ripples represent a key network signature believed to be important in memory consolidation. These network events have been largely studied in the hippocampus and are suppressed by the basal forebrain cholinergic system. Sharp wave ripples also occur in the basolateral amygdala, a region critically involved in emotional memory consolidation. Here, we show a novel mechanism by which low frequency stimulation of synaptic acetylcholine in basolateral amygdala brain slices can reliably induce sharp wave ripples through a nicotinic receptor-mediated mechanism. These findings update the view of neuromodulatory systems in sharp wave ripple induction, moving past a purely modulatory role for these systems and instead establish a role where modulators, like acetylcholine, can directly drive SWRs with temporal precision.
