Multiple spaced trials of aversive differential conditioning can produce two independent long-term memories (LTMs) of opposite valence. One is an aversive memory for avoiding the conditioned stimulus (CS+), and the other is a safety memory for approaching the non-conditioned stimulus (CS-). Here, we show that a single trial of aversive differential conditioning yields one merged LTM (mLTM) for avoiding both CS+ and CS-. Such mLTM can be detected after sequential exposures to the shock-paired CS+ and unpaired CS-, and be retrieved by either CS+ or CS-. The formation of mLTM relies on triggering aversive-reinforcing dopaminergic neurons and subsequent new protein synthesis. Expressing mLTM involves αβ Kenyon cells and corresponding approach-directing mushroom body output neurons (MBONs), in which similar-amplitude long-term depression of responses to CS+ and CS- seems to signal the mLTM. Our results suggest that animals can develop distinct strategies for occasional and repeated threatening experiences.
All data generated or analysed during this study are included in the manuscript and supporting files.
- Qian Li
- Yi Zhong
The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication.
- K VijayRaghavan, National Centre for Biological Sciences, Tata Institute of Fundamental Research, India
© 2021, Zhao 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.
Neutral events preceding emotional experiences can be better remembered, likely by assigning them as significant to guide possible use in future. Yet, the neurobiological mechanisms of how emotional learning enhances memory for past mundane events remain unclear. By two behavioral studies and one functional magnetic resonance imaging study with an adapted sensory preconditioning paradigm, we show rapid neural reactivation and connectivity changes underlying emotion-charged retroactive memory enhancement. Behaviorally, emotional learning enhanced initial memory for neutral associations across the three studies. Neurally, emotional learning potentiated trial-specific reactivation of overlapping neural traces in the hippocampus and stimulus-relevant neocortex. It further induced rapid hippocampal-neocortical functional reorganization supporting such retroactive memory benefit, as characterized by enhanced hippocampal-neocortical coupling modulated by the amygdala during emotional learning, and a shift of hippocampal connectivity from stimulus-relevant neocortex to transmodal prefrontal-parietal areas at post-learning rests. Together, emotional learning retroactively promotes memory integration for past neutral events through stimulating trial-specific reactivation of overlapping representations and reorganization of associated memories into an integrated network to foster its priority for future use.
The organization of neural circuits determines nervous system function. Variability can arise during neural circuit development (e.g. neurite morphology, axon/dendrite position). To ensure robust nervous system function, mechanisms must exist to accommodate variation in neurite positioning during circuit formation. Previously, we developed a model system in the Drosophila ventral nerve cord to conditionally induce positional variability of a proprioceptive sensory axon terminal, and used this model to show that when we altered the presynaptic position of the sensory neuron, its major postsynaptic interneuron partner modified its dendritic arbor to match the presynaptic contact, resulting in functional synaptic input (Sales et al., 2019). Here, we investigate the cellular mechanisms by which the interneuron dendrites detect and match variation in presynaptic partner location and input strength. We manipulate the presynaptic sensory neuron by (a) ablation; (b) silencing or activation; or (c) altering its location in the neuropil. From these experiments we conclude that there are two opposing mechanisms used to establish functional connectivity in the face of presynaptic variability: presynaptic contact stimulates dendrite outgrowth locally, whereas presynaptic activity inhibits postsynaptic dendrite outgrowth globally. These mechanisms are only active during an early larval critical period for structural plasticity. Collectively, our data provide new insights into dendrite development, identifying mechanisms that allow dendrites to flexibly respond to developmental variability in presynaptic location and input strength.