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ScienceWeek
NEUROSCIENCE: ON THE PLASTICITY OF VISUAL CORTEX
The following points are made by Frank Sengpiel (Current Biology 2005 15:R1000):
1) It is a well-known dogma of neuroscience that the adult mammalian brain has little or no capacity to regenerate or repair after injury. Equally, if adequate stimulation is lacking during a critical or sensitive period in early childhood, certain cortical functions, such as sight or language, will never develop properly later on. Now, several converging lines of research suggest that the ability of the brain to undergo regeneration or plastic changes does not simply fade away as we grow older, but is actively inhibited, and that a number of the factors which prevent regeneration in the adult brain are also involved in the closure of the critical period. The dual role of one of those inhibitors, the myelin-associated protein Nogo-A (Nogo for short), is highlighted in a recent study of experience-dependent plasticity in the mouse visual cortex [1].
2) Nogo-A was first discovered in the myelin sheath of spinal-cord axons, where it is located on the periaxonal side, in close proximity to the axons. It is recognized by the Nogo receptor NgR, which is present on the extracellular side of the neuronal membrane. Intracellular signalling appears to be mediated through the low-affinity neurotrophin receptor p75, with which NgR forms a complex and through which it activates the Rho pathway. The GTPase Rho and its effector, Rho kinase (ROCK) are important regulators of the actin cytoskeleton, and their activation causes growth cone collapse and inhibits axonal growth [2]. Hence, Nogo is a major contributor to the failure of the spinal cord to recover from injury, despite some initial axonal sprouting [3]. But what do Nogo and NgR have to do with experience-dependent plasticity of the visual cortex? Quite a lot, according to a recent study[1].
4) McGee et al[1] tested the hypothesis that intracortical myelin, via Nogo/NgR, blocks cortical plasticity by inhibiting neurite outgrowth, similar to the way it blocks axonal regeneration after spinal cord injury. They first characterized the density and laminar distribution of NgR and its ligands in mouse visual cortex. While total levels of myelin as well as of NgR increased only slightly during the critical period, layer 4 (where inputs from the two eyes arrive) showed the greatest increase in myelin. They then assessed the effects of four days of monocular deprivation in normal mice as compared with mutants lacking either Nogo-A [4] or NgR [5]. Normally reared mutant mice exhibited normal responses to visual stimulation and a normal ocular dominance profile. When monocularly deprived during the critical period (starting at age 24 days), they showed the same shift in ocular dominance towards the open eye as wild-type mice. Crucially, when monocular deprivation was imposed after the end of the critical period (aged 45 days), as determined in normal mice, the mice lacking Nogo or NgR exhibited an undiminished ocular dominance shift, while the wild-type mice showed no such shift. This result did not simply reflect a delay in the time course of the critical period, as a pronounced ocular dominance shift was seen even when deprivation was imposed in four-month-old mice. The absence of either Nogo or NgR thus prevents the closure of the critical period and preserves plasticity, perhaps indefinitely.
References (abridged):
1 A.W. McGee, Y. Yang, Q.S. Fischer, N.W. Daw and S.M. Strittmatter, Experience-driven plasticity of visual cortex limited by myelin and Nogo receptor, Science 309 (2005), pp. 2222 2226.
2 B. Niederöst, T. Oertle, J. Fritsche, R.A. McKinney and C.E. Bandtlow, Nogo-A and myelin-associated glycoprotein mediate neurite growth inhibition by antagonistic regulation of RhoA and Rac1, J. Neurosci. 22 (2002), pp. 10368 10376.
3 M.E. Schwab, Nogo and axon regeneration, Curr. Opin. Neurobiol. 14 (2004), pp. 118 124
4 J.E. Kim, S. Li, T. GrandPre, D. Qiu and S.M. Strittmatter, Axon regeneration in young adult mice lacking Nogo-A/B, Neuron 38 (2003), pp. 187 199
5 J.E. Kim, B.P. Liu, J.H. Park and S.M. Strittmatter, Nogo-66 receptor prevents raphespinal and rubrospinal axon regeneration and limits functional recovery from spinal cord injury, Neuron 44 (2004), pp. 439 451
Current Biology http://www.current-biology.com
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NEUROSCIENCE: ON PLASTICITY OF THE CEREBRAL CORTEX
The following points are made by M. Sur and J.L. Rubenstein (Science 2005 310:805):
1) The cerebral cortex of the human brain is a sheet of about 10 billion neurons divided into discrete subdivisions or areas that process particular aspects of sensation, movement, and cognition. Recent evidence has begun to transform our understanding of how cortical areas form, make specific connections with other brain regions, develop unique processing networks, and adapt to changes in inputs.
2) The degree to which our genetic endowment (nature) versus our experiences (nurture) mold the development and function of our brains has been the subject of robust discussion and experimental investigation. Research before 1990 led to two general hypotheses: the Protomap [1] and the Protocortex [2]. In their most extreme interpretations, the former postulated that the cortical progenitor zone contains the information that generates cortical areas, whereas the latter postulated that thalamic afferent axons, through activity-dependent mechanisms, impose cortical areal identity on an otherwise homogeneous cortex. In the intervening 15 years, tremendous strides have been made in understanding cortical development with molecular, genetic, imaging, and electrophysiological approaches. The new evidence indicates that the development of cortical areas involves a rich array of signals, with considerable interplay between mechanisms intrinsic to cortical progenitors and neurons and mechanisms extrinsic to the cortex, including those requiring neural activity.
3) Early development of the cortex is highly integrated with development of other parts of the brain, including midline patterning centers, the basal ganglia primordia that produce many of the cortical local circuit neurons, and axonal inputs from the thalamus and brain stem. The cortex, more generally known as the pallium, develops from a morphologically uniform ventricular zone located in the dorsocaudal part of the telencephalic vesicles. The pallium is further subdivided into medial pallium (MP), dorsal pallium (DP), lateral pallium (LP), and ventral pallium (VP), which will respectively give rise to the hippocampal formation (limbic lobe), the neocortex, the olfactory/piriform cortex, and the claustrum and parts of the amygdala [3,4]. Each of these large domains is divided into subdomains, such as the functional subdivisions (areas) of the neocortex.
4) Mature cortical areas differ by their location within the cortex, molecular properties, histological organization, patterns of connectivity, and function. Within the neocortex, rostral regions regulate motor and executive functions, whereas caudal regions process somatosensory, auditory, and visual inputs. These different cortical areas have a precise connectivity, particularly with nuclei within the dorsal thalamus, which provides some of the principal inputs to the cerebral cortex.
5) In summary: The Protomap/Protocortex controversy no longer remains: It is clear that the parcellation of the cerebral cortex into discrete processing areas involves an interwoven cascade of developmental events including both intrinsic and extrinsic mechanisms. The field now has the intellectual foundation and tools that will enable it to elucidate more complex features of cortical development, such as the formation of higher order cortical areas and circuits (which are a robust feature of the primate brain) and the lateralization of cortical functions (136). Insights gained from such studies will undoubtedly facilitate understanding of the mechanisms underlying the evolution of neural systems that control cognition and emotion as well as the etiologies of disorders that derail them.
References (abridged):
1. P. Rakic, Science 241, 170 (1988)
2. D. D. O'Leary, Trends Neurosci. 12, 400 (1989)
3. S. Garel, J. L. R. Rubenstein, in The Cognitive Neurosciences, M. S. Gazzaniga, Ed. (MIT Press, Cambridge, MA, ed. 3rd, 2004), pp. 69 84
4. L. Puelles, J. L. Rubenstein, Trends Neurosci. 26, 469 (2003)
5. P. H. Crossley, S. Martinez, Y. Ohkubo, J. L. Rubenstein, Neuroscience 108, 183 (2001)
Science http://www.sciencemag.org
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PLASTICITY OF AUDITORY CORTEX IN CONGENITALLY DEAF ANIMALS
Notes by ScienceWeek:
In general, the brains of animals and humans are organized in layers, the most recently evolved structures added on top of the older structures. The cerebral cortex is the most exterior part of the human brain, and also the most recently evolved region. The cortex is a thin surface layering of nerve cells, the region only several millimeters thick but covering all of the brain surface. This is the part of the central nervous system most intimately involved with the so-called "higher faculties", although the cortex operates in concert with other parts of the brain. The structure is primitive in lower mammals, and is found progressively more pronounced and with greater surface area in primates and man.
In addition to involvement with higher faculties, the cerebral cortex also contains several primary receiving areas for various sensory modalities, these regions of the cortex essentially acting as topographic maps of sensory input, maps that apparently organize input data into patterns meaningful for connected analytical regions. Two outstanding features of the cerebral cortex are its capacity for self-organization ("self-wiring") and its plasticity (in general, the ability of specific loci to alter function in response to previous experience).
In all sensory modalities, self-organization and plasticity depend on external stimuli. During development of the nervous system in a single individual, critical periods apparently exist during which an external influence is required to trigger the subsequent steps of central development. The criticality of these periods is made clear by the demonstrated arrested development that results from sensory deprivation during the critical periods. This aspect of neurological development is of particular importance in congenitally deaf patients, whose deafness can now in certain cases be treated by implants in the auditory sensory organ (cochlear implants).
When adults who are congenitally or prelingually deaf receive cochlear implants, the results are disappointing: these patients never gain language competence and often request that the implants be removed. In contrast, early cochlear implantation in congenitally or prelingually deafened children can lead to nearly perfect acoustic communication and language competence. What is not known, however, is the neurological basis underlying this phenomenon. Since certain types of experiments in humans are obviously not feasible, much research in the area has focused on animal models.
In congenitally deaf cats, the central auditory system is deprived of acoustic input because of degeneration of the auditory sensory organ cell system (the organ of Corti) before the onset of hearing. But auditory neurons that propagate activity to the brain (primary auditory afferents) survive under these conditions and can be stimulated electrically in appropriate experiments.
The following points are made by R. Klinke et al (Science 1999 285:1729):
1) The authors report that by means of an intracochlear implant and an accompanying sound processor, congenitally deaf kittens were exposed to sounds and conditioned to respond to tones. After months of exposure to meaningful stimuli, the cortical activity in chronically implanted cats (i.e., cats with chronically implanted recording electrodes) produced electric field potentials of higher amplitudes and expanded in area, developed long latency responses indicative of intracortical information processing, and showed more evidence of neuron connection efficacy than was observed in naive and unstimulated deaf cats.
2) This activity established by auditory experience in congenitally deaf animals resembles activity found in hearing animals. The authors suggest their results indicate that although without afferent input the auditory cortex remains rudimentary, this deficiency can be overcome by reafferentation (i.e, rewiring of input) to the deprived auditory channel by substitution of the missing cochlear activity. After implantation, a continuous input of relevant acoustic stimuli mimicking normal conditions results in animals displaying exploratory behavior, and animals that are attentive and motivated, factors known to strengthen cortical plasticity. The authors suggest a similar recruitment (i.e., organized activation) of the auditory cortex is likely to be the basis of demonstrated hearing acquisition in prelingually deaf human infants after early cochlear implantation.
Science http://www.sciencemag.org
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