Advances in neurobiology最新文献

Beta-endorphin is secreted from the hypothalamus and pituitary in both mother and newborn. The placenta produces numerous pituitary hormones from the third month of pregnancy, one of which is βE. It has been suggested that βE has a role in the appetitive and precopulatory phase of sexual behavior in animals. An increase in endorphin levels during sexual activity in humans may contribute to attachment and bonding between partners, but contradictory reports in the literature question the association between sexuality and βE levels. The level of βE also increases during pregnancy, rises in early labor, peaks in late labor, and drops in the postpartum period. This fluctuation provides natural analgesia, raises the pain threshold, decreases the sensation of pain, or suppresses pain, and decreases fear levels during labor and birth. Beta-endorphin also protects the fetus from hypoxia during labor and birth and potential neural damage by aiding blood flow to the brain under hypoxic conditions. It has been suggested that a variety of pharmacologic and nonpharmacologic complementary therapies, when used in pregnancy, labor, and birth, activate the opioid receptors in the CNS and alter the sensation of pain during labor and birth, affect the mother-child attachment and affect sexual function. These studies report contradictory results that will be discussed in this chapter.

Animals utilize a repertoire of behavioral responses during everyday experiences. During a potentially dangerous encounter, defensive actions such as "fight, flight, or freeze" are selected for survival. The successful use of behavior is determined by a series of real-time computations combining an animal's internal (i.e., body) and external (i.e., environment) state. Brain-wide neural pathways are engaged throughout this process to detect stimuli, integrate information, and command behavioral output. The hippocampus, in particular, plays a role in the encoding and storing of the episodic information surrounding these encounters as putative "engram" or experience-modified cellular ensembles. Recalling a negative experience then reactivates a dedicated engram ensemble and elicits a behavioral response. How hippocampus-based engrams modulate brain-wide states and an animal's internal/external milieu to influence behavior is an exciting area of investigation for contemporary neuroscience. In this chapter, we provide an overview of recent technological advancements that allow researchers to tag, manipulate, and visualize putative engram ensembles, with an overarching goal of casually connecting their brain-wide underpinnings to behavior. We then discuss how hippocampal fear engrams alter behavior in a manner that is contingent on an environment's physical features as well as how they influence brain-wide patterns of cellular activity. Overall, we propose here that studies on memory engrams offer an exciting avenue for contemporary neuroscience to casually link the activity of cells to cognition and behavior while also offering testable theoretical and experimental frameworks for how the brain organizes experience.

Engram labelling and manipulation methodologies are now a staple of contemporary neuroscientific practice, giving the impression that the physical basis of engrams has been discovered. Despite enormous progress, engrams have not been clearly identified, and it is unclear what they should look like. There is an epistemic bias in engram neuroscience toward characterizing biological changes while neglecting the development of theory. However, the tools of engram biology are exciting precisely because they are not just an incremental step forward in understanding the mechanisms of plasticity and learning but because they can be leveraged to inform theory on one of the fundamental mysteries in neuroscience-how and in what format the brain stores information. We do not propose such a theory here, as we first require an appreciation for what is lacking. We outline a selection of issues in four sections from theoretical biology and philosophy that engram biology and systems neuroscience generally should engage with in order to construct useful future theoretical frameworks. Specifically, what is it that engrams are supposed to explain? How do the different building blocks of the brain-wide engram come together? What exactly are these component parts? And what information do they carry, if they carry anything at all? Asking these questions is not purely the privilege of philosophy but a key to informing scientific hypotheses that make the most of the experimental tools at our disposal. The risk for not engaging with these issues is high. Without a theory of what engrams are, what they do, and the wider computational processes they fit into, we may never know when they have been found.

Multiple sclerosis (MS) is a devastating autoimmune disease that leads to profound disability. This disability arises from the stochastic, regional loss of myelin-the insulating sheath surrounding neurons-in the central nervous system (CNS). The demyelinated regions are dominated by the brain's resident macrophages: microglia. Microglia perform a variety of functions in MS and are thought to initiate and perpetuate demyelination through their interactions with peripheral immune cells that traffic into the brain. However, microglia are also likely essential for recruiting and promoting the differentiation of cells that can restore lost myelin in a process known as remyelination. Given these seemingly opposing functions, an overarching beneficial or detrimental role is yet to be ascribed to these immune cells. In this chapter, we will discuss microglia dynamics throughout the MS disease course and probe the apparent dichotomy of microglia as the drivers of both demyelination and remyelination.

Sleep is a physiological state that is essential for maintaining physical and mental health. Sleep disorders and sleep deprivation therefore have many adverse effects, including an increased risk of metabolic diseases and a decline in cognitive function that may be implicated in the long-term development of neurodegenerative diseases. There is increasing evidence that microglia, the resident immune cells of the central nervous system (CNS), are involved in regulating the sleep-wake cycle and the CNS response to sleep alteration and deprivation. In this chapter, we will discuss the involvement of microglia in various sleep disorders, including sleep-disordered breathing, insomnia, narcolepsy, myalgic encephalomyelitis/chronic fatigue syndrome, and idiopathic rapid-eye-movement sleep behavior disorder. We will also explore the impact of acute and chronic sleep deprivation on microglial functions. Moreover, we will look into the potential involvement of microglia in sleep disorders as a comorbidity to Alzheimer's disease and Parkinson's disease.

The temporal and spatial pattern of microglia colonization of the nervous system implies a role in early stages of organ development including cell proliferation, differentiation, and neurovascularization. As microglia colonize and establish within the developing nervous system, they assume a neural-specific identity and contribute to key developmental events. Their association around blood vessels implicates them in development of the vascular system or vice versa. A similar association has been reported for neural cell proliferation and associated phenotypic shifts and for cell fate differentiation to neuronal or glial phenotypes. These processes are accomplished by phagocytic activities, cell-cell contact relationships, and secretion of various factors. This chapter will present data currently available from studies evaluating the dynamic and interactive nature of these processes throughout the progression of nervous system development.

Astrocytes have gained increasing recognition as key elements of a broad array of nervous system functions. These include essential roles in synapse formation and elimination, synaptic modulation, maintenance of the blood-brain barrier, energetic support, and neural repair after injury or disease of the nervous system. Nevertheless, our understanding of mechanisms underlying astrocyte development and maturation remains far behind that of neurons and oligodendrocytes. Early efforts to understand astrocyte development focused primarily on their specification from embryonic progenitors and the molecular mechanisms driving the switch from neuron to glial production. Considerably, less is known about postnatal stages of astrocyte development, the period during which they are predominantly generated and mature. Notably, this period is coincident with synapse formation and the emergence of nascent neural circuits. Thus, a greater understanding of astrocyte development is likely to shed new light on the formation and maturation of synapses and circuits. Here, we highlight key foundational principles of embryonic and postnatal astrocyte development, focusing largely on what is known from rodent studies.

The first line of defense for the central nervous system (CNS) against injury or disease is provided by microglia. Microglia were long believed to stay in a dormant/resting state, reacting only to injury or disease. This view changed dramatically with the development of modern imaging techniques that allowed the study of microglial behavior in the intact brain over time, to reveal the dynamic nature of their responses. Over the past two decades, in vivo imaging using multiphoton microscopy has revealed numerous new functions of microglia in the developing, adult, aged, injured, and diseased CNS. As the most dynamic cells in the brain, microglia continuously contact all structures and cell types, such as glial and vascular cells, neuronal cell bodies, axons, dendrites, and dendritic spines, and are believed to play a central role in sculpting neuronal networks throughout life. Following trauma, or in neurodegenerative or neuroinflammatory diseases, microglial responses range from protective to harmful, underscoring the need to better understand their diverse roles and states in different pathological conditions. In this chapter, we introduce multiphoton microscopy and discuss recent advances in structural and functional imaging technologies that have expanded our toolbox to study microglial states and behaviors in new ways and depths. We also discuss relevant mouse models available for in vivo imaging studies of microglia and review how such studies are constantly refining our understanding of the multifaceted role of microglia in the healthy and diseased CNS.

Microglia have been implicated in numerous neurodegenerative and neuroinflammatory disorders; however, the causal contribution of this immune cell type is frequently debated. Genetic studies offer a unique vantage point in that they infer causality over a secondary consequence. Genome-wide association studies (GWASs) have identified hundreds of loci in the genome that are associated with susceptibility to neurodegenerative disorders. GWAS studies implicate microglia in the pathogenesis of Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and to a lesser degree suggest a role for microglia in vascular dementia (VaD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), and other neurodegenerative and neuropsychiatric disorders. The contribution and function of GWAS risk loci on disease progression is an ongoing field of study, in which large genomic datasets, and an extensive framework of computational tools, have proven to be crucial. Several GWAS risk loci are shared between disorders, pointing towards common pleiotropic mechanisms. In this chapter, we introduce key concepts in GWAS and post-GWAS interpretation of neurodegenerative disorders, with a focus on GWAS risk genes implicated in microglia, their interplay with other cell types and shared convergence of GWAS risk loci on microglia.

After the previous sections on "Fractals: What and Why?," the last section of this book covers the software tools necessary to perform computational fractal-based analysis, with special emphasis on its applications into the neurosciences. The use of ImageJ and MATLAB, as well as other software packages, is reviewed. The current and future applications of fractal modeling in bioengineering and biotechnology are discussed as well. Perspectives on the translation of merging fractals with artificial intelligence-based methods with the final aim of pattern discrimination in neurological diseases by means of a unified fractal model of the brain are also given. Moreover, some new translational applications of fractal analysis to the neurosciences are presented, including eye tracking analysis, cognitive neuroscience, and music.