Probing Acetylcholine Signaling Timescales
Fatemeh Farokhi Moghadam, Blanca Erika Gutiérrez-Guzmán, Xihui Zheng, Mina Parsa, Lojy Maged Hozyen, and Holger Dannenberg
(see article e0133252025)
Acetylcholine signaling in the septo-hippocampal pathway supports behaviors and cognitive functions such as memory. But memory acquisition involves neurotransmission at a variety of timescales. What are the dynamics of acetylcholine neurotransmission? In this issue, Farokhi Moghadam et al. used fiber photometry in mice to measure acetylcholine signaling at subsecond timescales as the mice performed a memory task. The authors discovered that acetylcholine signaling in the septo-hippocampal pathway occurred at a range of timescales. Fast signaling correlated with transient visits to new object locations, body movements, running speed, and transitioning between behavioral states. Slower timescales of signaling were associated with changes in environments. According to the authors, this work advances understanding of how acetylcholine supports acquisition and retrieval of memories across multiple timescales during navigation.
Shown is a calcium indicator expressed only in cholinergic neurons. Green indicates jGCaMP7/8 fluorescence, magenta indicates a marker for cholinergic neurons, and white shows colocalization. See Farokhi Moghadam et al. for more information.
How Interictal Spikes Impair Memory in Epilepsy
Justin D. Yi, Maryam Pasdarnavab, Laura Kueck, Gergely Tarcsay, and Laura A. Ewell
(see article e0193252025)
People with temporal lobe epilepsy experience interictal spikes, which are synchronous bursts of neural activity in the hippocampus that occur between seizures. Do interictal spikes influence hippocampal-mediated memory? Yi, Pasdarnavab, and colleagues recorded hippocampal activity in a mouse model of epilepsy as male mice pursued rewards in a maze. Interictal spikes correlated with worse task performance depending on where the spikes occurred with regard to the task. When the hippocampal spiking activity occurred in reward-related areas of the maze, mice performed the task successfully. The authors used machine learning to discover that interictal spikes at reward-related maze sites were stronger than when the spikes occurred in non-reward-related areas. Providing more mechanistic insight, a neural network model showed that when this spiking occurred in spatially dispersed areas as mice freely roamed the maze, it disrupted hippocampal replay of salient areas to worsen task performance. These findings suggest that interictal spikes can indeed impair memory but this impairment depends on external spatial context.
Footnotes
This Week in The Journal was written by Paige McKeon
