Wnt signaling regulates experience-dependent synaptic plasticity in the adult nervous system

Comment on: Jensen M, et al. Cell 2012; 149:173-87.     

Wnt signaling regulates experience-dependent synaptic plasticity in the adult nervous system

Comment on: Jensen M, et al. Cell 2012; 149:173-87.     

Calcium ions and the nervous system plasticity

The nervous system is different from all other systems of the organism by extreme flexibility of the structural and functional properties of its elements. This unique feature of the nervous system can be best described as plasticity in a broad sense of the word. All forms of plastic changes in the nervous system functioning have common basic mechanisms, the changes at the free Ca2+ cytosol ions being the most important one. These "calcium signals" trigger an extremely complicated intracellular machinery capable of controlling the structural and functional properties of the nervous system during the whole life span. This review summarises data on the intracellular Ca2+ ions mechanisms controlling the developmental plasticity of neuronal elements, synaptic plasticity of the mature nervous system, and the decline of plastic capabilities with ageing.     

Genetic control of experience-dependent plasticity in the visual cortex

Depriving one eye of visual experience during a sensitive period of development results in a shift in ocular dominance (OD) in the primary visual cortex (V1). To assess the heritability of this form of cortical plasticity and identify the responsible gene loci, we studied the influence of monocular deprivation on OD in a large number of recombinant inbred mouse strains derived from mixed C57BL/6J and DBA/2J backgrounds (BXD). The strength of imaged intrinsic signal responses in V1 to visual stimuli was strongly heritable as were various elements of OD plasticity. This has important implications for the use of mice of mixed genetic backgrounds for studying OD plasticity. C57BL/6J showed the most significant shift in OD, while some BXD strains did not show any shift at all. Interestingly, the increase in undeprived ipsilateral eye responses was not correlated to the decrease in deprived contralateral eye responses, suggesting that the size of these components of OD plasticity are not genetically controlled by only a single mechanism. We identified a quantitative trait locus regulating the change in response to the deprived eye. The locus encompasses 13 genes, two of which--Stch and Nrip1--contain missense polymorphisms. The expression levels of Stch and to a lesser extent Nrip1 in whole brain correlate with the trait identifying them as novel candidate plasticity genes.     

Molecular mechanisms of experience-dependent plasticity in visual cortex

A remarkable amount of our current knowledge of mechanisms underlying experience-dependent plasticity during cortical development comes from study of the mammalian visual cortex. Recent advances in high-resolution cellular imaging, combined with genetic manipulations in mice, novel fluorescent recombinant probes, and large-scale screens of gene expression, have revealed multiple molecular mechanisms that underlie structural and functional plasticity in visual cortex. We situate these mechanisms in the context of a new conceptual framework of feed-forward and feedback regulation for understanding how neurons of the visual cortex reorganize their connections in response to changes in sensory inputs. Such conceptual advances have important implications for understanding not only normal development but also pathological conditions that afflict the central nervous system.     

A comparison of experience-dependent plasticity in the visual and somatosensory systems

In the visual and somatosensory systems, maturation of neuronal circuits continues for days to weeks after sensory stimulation occurs. Deprivation of sensory input at various stages of development can induce physiological, and often structural, changes that modify the circuitry of these sensory systems. Recent studies also reveal a surprising degree of plasticity in the mature visual and somatosensory pathways. Here, we compare and contrast the effects of sensory experience on the connectivity and function of these pathways and discuss what is known to date concerning the structural, physiological, and molecular mechanisms underlying their plasticity.     

Critical periods in the visual system: changing views for a model of experience-dependent plasticity

Visual system circuitry, a canonical model system for the study of experience-dependent development, matures before and following the onset of vision. Sensory experience or deprivation during an early critical period results in substantial plasticity and is a crucial factor in establishing the mature circuitry. In adulthood, plasticity has been thought to be reduced or absent. However, recent studies point to the potential for change in neuronal circuits within the mature brain, raising the possibility that aberrant circuit function can be corrected. In this review, we will discuss recent exciting findings in the field of experience-dependent plasticity that advance our understanding of mechanisms underlying the activation, expression, and closure of critical periods in the visual system.     

Structural bases of the plasticity of the nervous system

The present state of morphological study of variability in the nervous elements under conditions of adaptive change under the influence of afferent effects, age changes during different periods of ontogenesis, under conditions of de- and regeneration of synapses have been considered. A question on correlation between structure and the function of synapses during the change has been analysed. The tasks of subsequent study of this problem have been outlined.     

Neuronal plasticity in the adult invertebrate nervous system

This essay provides a brief overview of neuronal plasticity in adult invertebrate nervous systems. Our discussion focuses on the factors which influence sprouting by adult neurons, i.e., (1) the nature of the neuron itself, (2) axon integrity, (3) the presence of targets, (4) diffusible factors, and (5) ageing. Evidence that the neurites of some adult neurons exhibit a dynamic equilibrium of expansion and retraction is presented, a topic which prompted us to speculate on the significance of such plasticity in altered behavioral states. We conclude with some suggestions as to specific questions that need to be addressed by future studies in this challenging area.     

Cholinergic modulation of experience-dependent plasticity in human auditory cortex

The factors that influence experience-dependent plasticity in the human brain are unknown. We used event-related functional magnetic resonance imaging (fMRI) and a pharmacological manipulation to measure cholinergic modulation of experience-dependent plasticity in human auditory cortex. In a differential aversive conditioning paradigm, subjects were presented with high (1600 Hz) and low tones (400 Hz), one of which was conditioned by pairing with an electrical shock. Prior to presentation, subjects were given either a placebo or an anticholinergic drug (0.4 mg iv scopolamine). Experience-dependent plasticity, expressed as a conditioning-specific enhanced BOLD response, was evident in auditory cortex in the placebo group, but not with scopolamine. This study provides in vivo evidence that experience-dependent plasticity, evident in hemodynamic changes in human auditory cortex, is modulated by acetylcholine.     

Taurine and central nervous system disorders

In the present era, investigators seek to find therapeutic interventions that are multifaceted in their mode of action. Such targets provide the most advantageous routes for addressing the multiplicity of pathophysiological avenues that lead to neuronal dysfunction and death observed in neurological disorders and neurodegenerative diseases. Taurine, an endogenous amino acid, exhibits a plethora of physiological functions in the central nervous system. In this review, we describe the mode of action of taurine and its clinical application in the neurological diseases: Alzheimer’s disease, Parkinson’s disease and Huntington’s disease.     

Spike timing-dependent LTP/LTD mediates visual experience-dependent plasticity in a developing retinotectal system

Sensory experience plays an instructive role in the development of the nervous system. Here we showed that visual experience can induce persistent modification of developing retinotectal circuits via spike timing-dependent plasticity (STDP). Pairing light stimuli with spiking of the tectal cell induced persistent enhancement or reduction of light-evoked responses, with a dependence on the relative timing between light stimulus and postsynaptic spiking similar to that for STDP. Using precisely timed sequential three-bar stimulation to mimic a moving bar, we showed that spike timing-dependent LTP/LTD can account for the asymmetric modification of the tectal cell receptive field induced by moving bar. Furthermore, selective inhibition of signaling mediated by brain-derived neurotrophic factor and nitric oxide, which are respectively required for light-induced LTP and LTD, interfered with moving bar-induced temporally specific changes in the tectal cell responses. Together, these findings suggest that STDP can mediate sensory experience-dependent circuit refinement in the developing nervous system.     

Circuit analysis of experience-dependent plasticity in the developing rat barrel cortex

Sensory deprivation during a critical period reduces spine motility and disrupts receptive field structure of layer 2/3 neurons in rat barrel cortex. To determine the locus of plasticity, we used laser scanning photostimulation, allowing us to rapidly map intracortical synaptic connectivity in brain slices. Layer 2/3 neurons differed in their spatial distributions of presynaptic partners: neurons directly above barrels received, on average, significantly more layer 4 input than those above the septa separating barrels. Complementary connectivity was found in deprived cortex: neurons above septa were now strongly coupled to septal regions, while connectivity between barrel regions and layer 2/3 was reduced. These results reveal competitive interactions between barrel and septal circuits in the establishment of precise intracortical circuits.