Updated November 30, 2021
Research Spotlight
Predictive Representations in Hippocampal and Prefrontal Hierarchies
How do our brains support planning and navigation of city-scale long distances? To address this question, the authors applied a novel analysis, using reinforcement learning models, to neuroimaging data collected while participants navigated long distances of several kilometers in a 3D virtual reality version of their hometown. The computational analysis revealed that multiscale predictive representations in the hippocampus and prefrontal cortex mediate navigation of realistically long distances. These representations simultaneously span the smallest-scale horizons in the hippocampus to largest-scale horizons in the prefrontal cortex. Anterior gradients in both regions cover longer predictive horizons. These findings offer a window into the neural underpinnings of navigation in everyday life.
Basal forebrain cholinergic neurons selectively drive coordinated motor learning in mice
Learning behavior that involves coordinated movements of fore- and hind-limbs requires the cooperative efforts of different motor centers within the brain. Li and Hollis found that the recruitment of these distant centers is dependent on activity of a small number of neurons in the basal forebrain that modulate large areas of the cortex by releasing acetylcholine. This neuromodulation is not required after the animals have learned the coordinated behavior. The neurons that produce acetylcholine are vulnerable in neurodegenerative diseases and may provide insight into movement disorders early in disease.
Learning and recovery from injuries depend on the plasticity of neuronal connections, while the brain’s extracellular matrix provides a scaffold stabilizing synaptic circuits. Matrix digestion promotes neuronal plasticity and is facilitated by a family of enzymes called matrix metalloproteinases (MMPs). Akol et al. demonstrate that treatments inhibiting two members of this enzyme family (MMP2/9) can either inhibit or rescue cortical plasticity depending on cortical state: in healthy adult mice, inhibition of MMP2/9 suppressed visual cortex plasticity, while brief inhibition of MMP2/9 after a distant stroke rescued compromised plasticity. These data strongly suggest that a tightly regulated level of the matrix digesting enzymes MMP2/9 is crucial for adult cortical plasticity.
Most-Discussed Research Published in October
Below are five Early Release articles that generated the most online discussion in October 2021, as measured by Altmetric. Altmetric data is available for all articles published in JNeurosci on the Info & Metrics tab. Learn more about how the Altmetric score is calculated.
Memory Reactivation During Sleep Improves Execution of a Challenging Motor Skill
Prior literature on motor learning has produced much evidence supporting a role for sleep, but scant evidence on the execution component. This aspect of learning is critical for many complex skills that people value in their lives. Our results not only implicate sleep in skill learning, but also pinpoint a benefit for motor execution using a method for modifying memory storage during sleep. We used targeted memory reactivation or TMR, whereby a stimulus that has been associated with learning is presented again during sleep to bring on a recapitulation of waking brain activity. Our demonstration that memory reactivation contributed to skilled performance may be relevant for neurorehabilitation as well as fields concerned with motor learning, such as kinesiology and physiology.
Understanding endogenous pain modulatory mechanisms would support development of effective clinical treatment strategies for both acute and chronic pain. Specific brainstem nuclei have long been known to play a central role in nociceptive modulation, however due to their small size and complex organization, previous neuroimaging efforts have been limited in directly identifying how these subcortical networks interact during the development of anti- and pro-nociceptive effects. We used ultra-high field fMRI to resolve brainstem structures and measure signal change during placebo analgesia and nocebo hyperalgesia. We define overlapping and disparate brainstem circuitry responsible for altering pain perception. These findings extend our understanding of the detailed organization and function of discrete brainstem nuclei involved in pain processing and modulation.
Developmental shifts in amygdala activity during a high social drive state
Social engagement during adolescence is a key component of healthy development. Social drive provides the impetus for social engagement and abnormalities underlie social symptoms of depression and anxiety. While adolescence is characterized by transitions in social drive and social environment sensitivity, little is known about the neural basis for these changes. We found that amygdala activity is uniquely sensitive to social environment during adolescence compared to adulthood, and is required for expression of heightened social drive. In addition, the neural substrates shift towards NMDA dependence in adulthood. These results are the first to demonstrate a unique neural signature of higher social drive and begin to uncover the underlying factors that heighten social engagement during adolescence.
Hippocampus-Prefrontal Coupling Regulates Recognition Memory for Novelty Discrimination
Many memory processes are highly dependent on the inter-regional communication between the HPC and mPFC via neural oscillations. However, how these two brain regions coordinate their oscillatory activity to engage local neural populations to mediate recognition memory for novelty discrimination is poorly understood. This study revealed that the HPC and mPFC theta oscillations and their temporal coupling is correlated with recognition memory-guided behaviour. During novel object recognition, the HPC drives mPFC interneurons to effectively reduce the activity of principal neurons. This study provides the first evidence for the requirement of the HPC-mPFC pathway to mediate recognition memory for novelty discrimination and describes a mechanism for how this memory is regulated.
Mechanosensory Stimulation via Nanchung Expressing Neurons Can Induce Daytime Sleep in Drosophila
Our tendency to fall asleep in moving vehicles or the practice of rocking infants to sleep suggests that slow rhythmic movement can induce sleep, although we do not understand the mechanistic basis of this phenomenon. We find that gentle orbital motion can induce behavioral quiescence even in flies, a highly genetically tractable system for sleep studies. We demonstrate that this is indeed true sleep based on its rapid reversibility by sensory stimulation, enhanced arousal threshold, and homeostatic control. Furthermore, we demonstrate that mechanosensory neurons expressing a TRPV channel nanchung, located in the antennae and chordotonal organs, mediate orbital motion-induced sleep by communicating with antennal mechanosensory motor centers, which in turn may project to sleep centers in the brain.
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