'Sundowning' in dementia and Alzheimer's disease is characterized by early-evening agitation and aggression. While such periodicity suggests a circadian origin, whether the circadian clock directly ...regulates aggressive behavior is unknown. We demonstrate that a daily rhythm in aggression propensity in male mice is gated by GABAergic subparaventricular zone (SPZ
) neurons, the major postsynaptic targets of the central circadian clock, the suprachiasmatic nucleus. Optogenetic mapping revealed that SPZ
neurons receive input from vasoactive intestinal polypeptide suprachiasmatic nucleus neurons and innervate neurons in the ventrolateral part of the ventromedial hypothalamus (VMH), which is known to regulate aggression. Additionally, VMH-projecting dorsal SPZ neurons are more active during early day than early night, and acute chemogenetic inhibition of SPZ
transmission phase-dependently increases aggression. Finally, SPZ
-recipient central VMH neurons directly innervate ventrolateral VMH neurons, and activation of this intra-VMH circuit drove attack behavior. Altogether, we reveal a functional polysynaptic circuit by which the suprachiasmatic nucleus clock regulates aggression.
The posterior parietal cortex and frontal cortical areas to which it connects are responsible for sensorimotor transformations. This review covers new research on four components of this ...transformation process: planning, decision making, forward state estimation, and relative-coordinate representations. These sensorimotor functions can be harnessed for neural prosthetic operations by decoding intended goals (planning) and trajectories (forward state estimation) of movements as well as higher cortical functions related to decision making and potentially the coordination of multiple body parts (relative-coordinate representations).
Adaptation is fundamental to life. All organisms adapt over timescales that span from evolution to generations and lifetimes to moment-by-moment interactions. The nervous system is particularly adept ...at rapidly adapting to change, and this in fact may be one of its fundamental principles of organization and function. Rapid forms of sensory adaptation have been well documented across all sensory modalities in a wide range of organisms, yet we do not have a comprehensive understanding of the adaptive cellular mechanisms that ultimately give rise to the corresponding percepts, due in part to the complexity of the circuitry. In this Perspective, we aim to build links between adaptation at multiple scales of neural circuitry by investigating the differential adaptation across brain regions and sub-regions and across specific cell types, for which the explosion of modern tools has just begun to enable. This investigation points to a set of challenges for the field to link functional observations to adaptive properties of the neural circuit that ultimately underlie percepts.
In this Perspective, Whitmire and Stanley build links between rapid sensory adaptation at multiple scales of neural circuitry through investigations of differential adaptation effects across brain structures, cell types, and functional classes of neurons.
Learning to predict rewards based on environmental cues is essential for survival. The orbitofrontal cortex (OFC) contributes to such learning by conveying reward-related information to brain areas ...such as the ventral tegmental area (VTA). Despite this, how cue-reward memory representations form in individual OFC neurons and are modified based on new information is unknown. To address this, using in vivo two-photon calcium imaging in mice, we tracked the response evolution of thousands of OFC output neurons, including those projecting to VTA, through multiple days and stages of cue-reward learning. Collectively, we show that OFC contains several functional clusters of neurons distinctly encoding cue-reward memory representations, with only select responses routed downstream to VTA. Unexpectedly, these representations were stably maintained by the same neurons even after extinction of the cue-reward pairing, and supported behavioral learning and memory. Thus, OFC neuronal activity represents a long-term cue-reward associative memory to support behavioral adaptation.
It has been hypothesized that to perform sensorimotor transformations efficiently, somatosensory information being fed back to a particular motor circuit is organized in accordance with the ...mechanical loading patterns of the skin that result from the motor activity generated by that circuit. Rearrangements of sensory information to different motor circuits could in this respect constitute a key component of sensorimotor learning. We here explored whether the organization of tactile input from the plantar forepaw of the rat to cortical and striatal circuits is affected by a period of extensive sensorimotor training in a skilled reaching and grasping task. Our data show that the representation of tactile stimuli in terms of both temporal and spatial response patterns changes as a consequence of the training and that spatial changes particularly involve the primary motor cortex. Based on the observed reorganization, we propose that reshaping of the spatiotemporal representation of the tactile afference to motor circuits is an integral component of the learning process that underlies skill acquisition in reaching and grasping.
Sensorimotor transformations are fundamental to the function of the nervous system and determine how patterns of sensory input are converted into appropriate movements. We here investigated the extent to which experience-dependent processes can reshape the organization of somatosensory input feeding into cortico-basal ganglia motor structures. Our data point to a particularly important role for the primary motor cortex in the functional adaptions associated with skilled motor learning.
The gentle touch receptors of mammalian skin Zimmerman, Amanda; Bai, Ling; Ginty, David D.
Science (American Association for the Advancement of Science),
11/2014, Volume:
346, Issue:
6212
Journal Article
Peer reviewed
Open access
The skin is our largest sensory organ, transmitting pain, temperature, itch, and touch information to the central nervous system. Touch sensations are conveyed by distinct combinations of ...mechanosensory end organs and the low-threshold mechanoreceptors (LTMRs) that innervate them. Here we explore the various structures underlying the diverse functions of cutaneous LTMR end organs. Beyond anchoring of LTMRs to the surrounding dermis and epidermis, recent evidence suggests that the non-neuronal components of end organs play an active role in signaling to LTMRs and may physically gate force-sensitive channels in these receptors. Combined with LTMR intrinsic properties, the balance of these factors comprises the response properties of mechanosensory neurons and, thus, the neural encoding of touch.
Cell-associated proteoglycans provide highly complex and sophisticated systems to control interactions of extracellular cell matrix components and soluble ligands with the cell surface. Syndecans, a ...conserved family of heparan- and chondroitin-sulfate carrying transmembrane proteins, are emerging as central players in these interactions. Recent studies have demonstrated the essential role of syndecans in modulating cellular signaling in embryonic development, tumorigenesis, and angiogenesis. In this review, we focus on new advances in our understanding of syndecan-mediated cell signaling.
Hippocampal place cells are key to episodic memories. How these cells participate in memory retrieval remains unclear. After rats acquired a fear memory by receiving mild footshocks in a shock zone ...on a track, we analyzed place cells when the animals were placed on the track again and displayed an apparent memory retrieval behavior: avoidance of the shock zone. We found that place cells representing the shock zone were reactivated, despite the fact that the animals did not enter the shock zone. This reactivation occurred in ripple-associated awake replay of place cell sequences encoding the paths from the animal's current positions to the shock zone but not in place cell sequences within individual cycles of theta oscillation. The result reveals a specific place-cell pattern underlying inhibitory avoidance behavior and provides strong evidence for the involvement of awake replay in fear memory retrieval.
Over the past 10 years, researchers have studied the effects of recreational football training as a health-promoting activity for participants across the lifespan. This has important public health ...implications as over 400 million people play football annually. Results from the first randomised controlled trial, published in the BJSM in January 2009, showed that football increased maximal oxygen uptake and muscle and bone mass, and lowered fat percentage and blood pressure, in untrained men, and since then more than 70 articles about football for health have been published, including publications in two supplements of the Scandinavian Journal of Medicine and Science in Sports in 2010 and 2014, prior to the FIFA World Cup tournaments in South Africa and Brazil. While studies of football training effects have also been performed in women and children, this article reviews the current evidence linking recreational football training with favourable effects in the prevention and treatment of disease in adult men.
Microglia are increasingly recognized for their major contributions during brain development and neurodegenerative disease. It is currently unknown whether these functions are carried out by subsets ...of microglia during different stages of development and adulthood or within specific brain regions. Here, we performed deep single-cell RNA sequencing (scRNA-seq) of microglia and related myeloid cells sorted from various regions of embryonic, early postnatal, and adult mouse brains. We found that the majority of adult microglia expressing homeostatic genes are remarkably similar in transcriptomes, regardless of brain region. By contrast, early postnatal microglia are more heterogeneous. We discovered a proliferative-region-associated microglia (PAM) subset, mainly found in developing white matter, that shares a characteristic gene signature with degenerative disease-associated microglia (DAM). Such PAM have amoeboid morphology, are metabolically active, and phagocytose newly formed oligodendrocytes. This scRNA-seq atlas will be a valuable resource for dissecting innate immune functions in health and disease.
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•Myeloid scRNA-seq atlas across brain regions and developmental stages•Limited transcriptomic heterogeneity of homeostatic microglia in the adult brain•Phase-specific gene sets of proliferating microglia along cell cycle pseudotime•Phagocytic PAM subset uncovered by scRNA-seq sharing a DAM gene signature
Li et al. generate high-resolution single-cell transcriptomes of microglia and related myeloid cells across mouse brain regions and developmental stages. They show limited heterogeneity of adult microglia and identify an early postnatal phagocytic subset of proliferative-region-associated microglia (PAM).
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