Exercise is a potent enhancer of learning and memory, yet we know little of the underlying mechanisms that likely include alterations in synaptic efficacy in the hippocampus. To address this issue, we exposed mice to a single episode of voluntary exercise, and permanently marked activated mature hippocampal dentate granule cells using conditional Fos-TRAP mice. Exercise-activated neurons (Fos-TRAPed) showed an input-selective increase in dendritic spines and excitatory postsynaptic currents at 3 days post-exercise, indicative of exercise-induced structural plasticity. Laser-capture microdissection and RNASeq of activated neurons revealed that the most highly induced transcript was Mtss1L, a little-studied I-BAR domain-containing gene, which we hypothesized could be involved in membrane curvature and dendritic spine formation. shRNA-mediated Mtss1L knockdown in vivo prevented the exercise-induced increases in spines and excitatory postsynaptic currents. Our results link short-term effects of exercise to activity-dependent expression of Mtss1L, which we propose as a novel effector of activity-dependent rearrangement of synapses.
- Richard H Goodman
- Gary L Westbrook
- Eric Schnell
- Eric Schnell
- Richard H Goodman
- Wiiliam D Hendricks
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All procedures were performed according to the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals and were in compliance with approved IACUC protocols at Oregon Health & Science University (protocol# TR01-IP00000148). For surgeries, all mice were anesthetized using an isoflurane delivery system (Veterinary Anesthesia Systems Co.) by spontaneous respiration and every effort was made to minimize suffering.All investigators underwent institutional Responsible Conduct & Research training.
- John Huguenard, Stanford University School of Medicine, United States
© 2019, Chatzi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Downloads (link to download the article as PDF)
Download citations (links to download the citations from this article in formats compatible with various reference manager tools)
Open citations (links to open the citations from this article in various online reference manager services)
The prefrontal cortex (PFC) integrates incoming information to guide our actions. When motivation for food-seeking competes with avoidance of danger, the PFC likely plays a role in selecting the optimal choice. In platform-mediated active avoidance, rats avoid a tone-signaled footshock by stepping onto a nearby platform, delaying access to sucrose pellets. This avoidance requires prelimbic (PL) PFC, basolateral amygdala (BLA), and ventral striatum (VS). We previously showed that inhibitory tone responses of PL neurons correlate with avoidability of shock (Diehl et al., 2018). Here, we optogenetically modulated PL terminals in VS and BLA to identify PL outputs regulating avoidance. Photoactivating PL-VS projections reduced avoidance, whereas photoactivating PL-BLA projections increased avoidance. Moreover, photosilencing PL-BLA or BLA-VS projections reduced avoidance, suggesting that VS receives opposing inputs from PL and BLA. Bidirectional modulation of avoidance by PL projections to VS and BLA enables the animal to make appropriate decisions when faced with competing drives.
Diverse mechanosensory neurons detect different mechanical forces that can impact animal behavior. Yet our understanding of the anatomical and physiological diversity of these neurons and the behaviors that they influence is limited. We previously discovered that grooming of the Drosophila melanogaster antennae is elicited by an antennal mechanosensory chordotonal organ, the Johnston's organ (JO) (Hampel et al., 2015). Here, we describe anatomically and physiologically distinct JO mechanosensory neuron subpopulations that each elicit antennal grooming. We show that the subpopulations project to different, discrete zones in the brain and differ in their responses to mechanical stimulation of the antennae. Although activation of each subpopulation elicits antennal grooming, distinct subpopulations also elicit the additional behaviors of wing flapping or backward locomotion. Our results provide a comprehensive description of the diversity of mechanosensory neurons in the JO, and reveal that distinct JO subpopulations can elicit both common and distinct behavioral responses.