Synaptic Plasticity

Efforts to bridge emotion theory with neurobiology can be facilitated by dynamic systems (DS) modeling. DS principles stipulate higher-order wholes emerging from lower-order constituents through bidirectional causal processes – offering a common language for psychological and neurobiological models. After identifying some limitations of mainstream emotion theory, I apply DS principles to emotion–cognition relations. I then present a psychological model based on this reconceptualization, identifying trigger, self-amplification, and self-stabilization phases of emotion-appraisal states, leading to consolidating traits. The article goes on to describe neural structures and functions involved in appraisal and emotion, as well as DS mechanisms of integration by which they interact. These mechanisms include nested feedback interactions, global effects of neuromodulation, vertical integration, action-monitoring, and synaptic plasticity, and they are modeled in terms of both functional inte...

Huperzia saururus (Lam.) Trevis. (Lycopodiaceae) known as cola de quirquincho is used in folk medicine to improve memory. The cholinergic neurons of the basal forebrain, including those in the medial septum, and in the vertical limbs of the diagonal band of Broca and the nucleus basalis of Meynert, provide a major source of cholinergic enervation of the cortex and hippocampus. These neurons have also been shown to play an important role in learning and memory processes. Thus, the effects of this traditional Argentinean species were studied in relation to its activity on synaptic transmission in the hippocampus. The alkaloid extract obtained first by decoction of the aerial parts and by subsequent alkaline extraction, was purified by using a Sephadex LH 20 packed column.Electrophysiological experiments were developed with the purified extract (E2) on rat hippocampus slices, thus eliciting long-term potentiation (LTP). Results show a marked increase in the hippocampal synaptic plasticity. The threshold value for generation of LTP was 22 ± 1.01 Hz on average for E2, while for controls it was 86 ± 0.92 Hz. All of these factors could explain the use of Huperzia saururus as a memory improver as is reported in the ethnomedicine.

The adult brain is not as hard-wired as traditionally thought. By modifying their small- or large-scale morphology, neurons can make new synaptic connections or break existing ones (structural plasticity). Structural changes accompany memory formation and learning, and are induced by neurogenesis, neurodegeneration and brain injury such as stroke. Exploring the role of structural plasticity in the brain can be greatly assisted by mathematical and computational models, as they enable us to bridge the gap between system-level dynamics and lower level cellular and molecular processes. However, most traditional neural network models have fixed neuronal morphologies and a static connectivity pattern, with plasticity merely arising from changes in the strength of existing synapses (synaptic plasticity). In The Rewiring Brain, the editors bring together, for the first time, contemporary modeling studies that investigate the implications of structural plasticity for brain function and pathology. Starting with an experimental background on structural plasticity in the adult brain, the book covers computational studies on homeostatic structural plasticity, the impact of structural plasticity on cognition and cortical connectivity, the interaction between synaptic and structural plasticity, neurogenesis-related structural plasticity, and structural plasticity in neurological disorders. Structural plasticity adds a whole new dimension to brain plasticity, and The Rewiring Brain shows how computational approaches may help to gain a better understanding of the full adaptive potential of the adult brain. The book is written for both computational and experimental neuroscientists. Key features: • Reviews the current state of knowledge of structural plasticity in the adult brain. • Gives a comprehensive overview of computational studies on structural plasticity. • Provides insights into the potential driving forces of structural plasticity and the functional implications of structural plasticity for learning and memory. • Serves as inspiration for developing novel treatment strategies for stimulating functional repair after brain damage. For a preview and to order the book, go to: https://www.elsevier.com/books/the-rewiring-brain/van-ooyen/978-0-12-803784-3

The neuropathological correlates of Alzheimer's disease (AD) include amyloid-β (Aβ) plaques and neurofibrillary tangles. To study the interaction between Aβ and tau and their effect on synaptic function, we derived a triple-transgenic model (3×Tg-AD) harboring PS1M146V, APPSwe, and tauP301L transgenes. Rather than crossing independent lines, we microinjected two transgenes into single-cell embryos from homozygous PS1M146V knockin mice, generating mice with the same genetic background. 3×Tg-AD mice progressively develop plaques and tangles. Synaptic dysfunction, including LTP deficits, manifests in an age-related manner, but before plaque and tangle pathology. Deficits in long-term synaptic plasticity correlate with the accumulation of intraneuronal Aβ. These studies suggest a novel pathogenic role for intraneuronal Aβ with regards to synaptic plasticity. The recapitulation of salient features of AD in these mice clarifies the relationships between Aβ, synaptic dysfunction, and tangles and provides a valuable model for evaluating potential AD therapeutics as the impact on both lesions can be assessed.

Major depressive disorder (MDD) will affect one out of every five people in their lifetime and is the leading cause of disability worldwide. Nevertheless, mechanisms associated with the pathogenesis of MDD have yet to be completely understood and current treatments remain ineffective in a large subset of patients. In this review, we summarize the most recent discoveries and insights for which parallel findings have been obtained in human depressed subjects and rodent models of mood disorders in order to examine the potential etiology of depression. These mechanisms range from synaptic plasticity mechanisms to epigenetics and the immune system where there is strong evidence to support a functional role in the development of specific depression symptomology. Ultimately we conclude by discussing how novel therapeutic strategies targeting central and peripheral processes might ultimately aid in the development of effective new treatments for MDD and related stress disorders.

Modifications of neuronal circuits allow the brain to adapt and change with experience. This plasticity manifests during development and throughout life, and can be remarkably long lasting. Evidence has linked activity-regulated gene expression to the long-term structural and electrophysiological adaptations that take place during developmental critical periods, learning and memory, and alterations to sensory map representations in the adult. In all these cases, the cellular response to neuronal activity integrates multiple tightly coordinated mechanisms to precisely orchestrate long-lasting, functional and structural changes in brain circuits. Experience-dependent plasticity is triggered when neuronal excitation activates cellular signaling pathways from the synapse to the nucleus that initiate new programs of gene expression. The protein products of activity-regulated genes then work via a diverse array of cellular mechanisms to modify neuronal functional properties. Synaptic stre...

Mammalian excitatory synapses express diverse types of synaptic plasticity. A major challenge in neuroscience is to understand how a neuron utilizes different types of plasticity to sculpt brain development, function, and behavior. Neuronal activity-induced expression of the immediate early protein, Arc, is critical for long-term potentiation and depression of synaptic transmission, homeostatic synaptic scaling, and adaptive functions such as long-term memory formation. However, the molecular basis of Arc protein function as a regulator of synaptic plasticity and cognition remains a puzzle. Recent work on the biophys-ical and structural properties of Arc, its protein-protein interactions and post-translational modifications have shed light on the issue. Here, we present Arc protein as a flexible, multifunctional and interactive hub. Arc interacts with specific effector proteins in neuronal compartments (dendritic spines, nuclear domains) to bidirectionally regulate synaptic strength by distinct molecular mechanisms. Arc stability, subcellular localization, and interactions are dictated by synaptic activity and post-translational modification of Arc. This functional versatility and context-dependent signaling supports a view of Arc as a highly specialized master organizer of long-term synaptic plasticity, critical for information storage and cognition.

Light & Scent (People Relearn a Heightened Sense of Smell to Enhance Brain Plasticity)

We're born smellers.  Being enveloped in "womb-waters" means our smell sense is not fully-activated with the mechanisms for breathing air (replete with essential scent molecules) until we take that very first lung-filling breath.  In fact, the human olfactory system is increasingly understood to be highly dynamic. The neurobiological underpinnings of this plasticity, including “bottom-up” factors like regulation of peripheral odor receptors and “top-down” factors like the sensory consequences of emotional and cognitive states, are  really just beginning to be explored with regards to more therapeutic potentials. As the human olfactory bulb is actually quite large in absolute terms and contains a similar number of neurons to that of other mammals there's increasing awareness of engaging our excellent olfactory abilities to assist in trauma and rehabilitative recovery.  (Check out some recent discoveries about this topic to learn how and why we can detect and discriminate an extraordinary range of odors.)

~ http://www.natureandforesttherapy.org/blog/on-the-scent-of-wellness

​~ http://www.npr.org/sections/health-shots/2017/06/06/531744473/learn-to-sniff-the-world-like-a-dog-does-and-see-in-a-new-way​

~​Poor human olfaction is a 19th-century myth​
http://science.sciencemag.org/content/356/6338/eaam7263

In our mother, the foods she ingested and air she breathed, while being filtered, prepared us to emerge ready and able to smell:  with the mighty task @ hand -- singularly feeding.  We, alone, released from the umbilical, needed to seek out mother's nipple.  Scent being our pathfinder.  Though, in these earliest of "sniffings" we're also unleashing a slew of early and rapid neurological changes to bring the nose, eyes and even ears into a whole concerted/highly orchestrated neurological realm of learning, forever changing how we navigate and discover the essence of our brand new world.

Startle reflex is something everyone knows about.  We've all felt it at one time or another.  It is the response of our mind and our body from a sudden unexpected stimulus. When startled, our bodies go through many physical changes including contraction of muscles of the arm and leg, blinking, increase in blood pressure, respiration and breathing rate. While the muscle contraction responses generally resolve themselves in a matter of seconds, it often takes our breathing, respiration and blood pressure much more time to normalize.  In humans, this is typically measured by determining the magnitude of the muscle activity of the ​ eyeblink reflex​ during the emission of a sudden loud noise. (And this response is capitalized on in certain " eye-movement-based " PTS therapy approaches such as Eye-Movement Desensitization and Reprocessing (EMDR), Comprehensive Resource Model (CRM) and Accelerated Resolution Therapy (ART)).

The ability to carry out signal processing, classification, recognition, and computation in artificial spiking neural networks (SNNs) is mediated by their synapses. In particular, through activity-dependent alteration of their efficacies, synapses play a fundamental role in learning. The mathematical prescriptions under which synapses modify their weights are termed synaptic plasticity rules. These learning rules can be based on abstract computational neuroscience models or on detailed biophysical ones. As these rules are being proposed and developed by experimental and computational neuroscientists, engineers strive to design and implement them in silicon and en masse in order to employ them in complex real-world applications. In this paper, we describe analog very large-scale integration (VLSI) circuit implementations of multiple synaptic plasticity rules, ranging from phenomenological ones (e.g., based on spike timing, mean firing rates, or both) to biophysically realistic ones (e.g., calcium-dependent models). We discuss the application domains, weaknesses, and strengths of various representative approaches proposed in the literature , and provide insight into the challenges that engineers face when designing and implementing synaptic plasticity rules in VLSI technology for utilizing them in real-world applications.

Sensory systems adapt to environmental change. It has been argued that adaptation should have the effect of optimizing sensitivity to the new environment. Here we consider a framework in which this premise is made concrete using an economic normative theory of visual motion perception. In this framework, visual systems adapt to the environment by reallocating their limited neural resources. The allocation is optimal when uncertainties about different aspects of stimulation are balanced. This theory makes predictions about visual sensitivity as a function of environmental statistics. Adaptive optimization of the visual system should be manifested as a change in sensitivity for an observer and for the underlying motion-sensitive neurons. We review evidence supporting these predictions and examine effects of adaptation on the neuronal representation of visual motion.

Interactions between presynaptic and postsynaptic cellular adhesion molecules (CAMs) drive synapse maturation during development. These trans-synaptic interactions are regulated by alternative splicing of CAM RNAs, which ultimately determines neurotransmitter phenotype. The diverse assortment of RNAs produced by alternative splicing generates countless protein isoforms necessary for guiding specialized cell-to-cell connectivity. Failure to generate the appropriate synaptic adhesion proteins is associated with disrupted glutamatergic and gamma-aminobutyric acid signaling, resulting in loss of activity-dependent neuronal plasticity, and risk for developmental disorders, including autism. While the majority of genetic mutations currently linked to autism are rare variants that change the protein-coding sequence of synaptic candidate genes, regulatory polymorphisms affecting constitutive and alternative splicing have emerged as risk factors in numerous other diseases, accounting for an estimated 40–60% of general disease risk. Here, we review the relationship between aberrant RNA splicing of synapse-related genes and autism spectrum disorders.

Kainate receptors form a family of ionotropic glutamate receptors that appear to play a special role in the regulation of the activity of synaptic networks. This review first describes briefly the molecular and pharmacological properties of native and recombinant kainate receptors. It then attempts to outline the general principles that appear to govern the function of kainate receptors in the activity of synaptic networks under physiological conditions. It subsequently describes the way that kainate receptors are involved in synaptic integration, synaptic plasticity, the regulation of neurotransmitter release and the control of neuronal excitability, and the manner in which they might play an important role in synaptogenesis and synaptic maturation. These functions require the proper subcellular localization of kainate receptors in specific functional domains of the neuron, necessitating complex cellular and molecular trafficking events. We show that our comprehension of these mechanisms is just starting to emerge. Finally, this review presents evidence that implicates kainate receptors in pathophysiological conditions such as epilepsy, excitotoxicity and pain, and that shows that these receptors represent promising therapeutic targets.

Taller que apunta hacia tres objetivos:

a. Aprender acerca de la etimología de la palabra plasticidad.
b. Integrar la noción de plasticidad con la de morfología, cambio y metamorfosis.
c. Repasar el concepto de plasticidad que adopta la neurociencia.

Desde Goethe y Catherine Malabou hacia la neurociencia enfatizando sobre el carácter proteico de los procesos biológicos.

The hippocampal dentate gyrus plays a critical role in learning and memory throughout life, in part by the integration of adult-born neurons into existing circuits. Neurogenesis in the adult hippocampus is regulated by numerous environmental , physiological, and behavioral factors known to affect learning and memory. Sleep is also important for learning and memory. Here we critically examine evidence from correlation, deprivation, and stimulation studies that sleep may be among those factors that regulate hippocampal neurogenesis. There is mixed evidence for correlations between sleep variables and rates of hippocampal cell proliferation across the day, the year, and the lifespan. There is modest evidence that periods of increased sleep are associated with increased cell proliferation or survival. There is strong evidence that disruptions of sleep exceeding 24 h, by total deprivation , selective REM sleep deprivation, and chronic restriction or fragmentation, significantly inhibit cell proliferation and in some cases neurogenesis. The mechanisms by which sleep disruption inhibits neurogenesis are not fully understood. Although sleep disruption procedures are typically at least mildly stressful, elevated adrenal corticosterone secretion is not necessary for this effect. However, procedures that prevent both elevated corticosterone and interleukin 1b signaling have been found to block the effect of sleep deprivation on cell proliferation. This result suggests that sleep loss impairs hippocampal neurogenesis by the presence of wake-dependent factors, rather than by the absence of sleep-specific processes. This would weigh against a hypothesis that regulation of neurogenesis is a function of sleep. Nonetheless, impaired neurogenesis may underlie some of the memory and mood effects associated with acute and chronic sleep disruptions.