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ScienceWeek
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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Related Material:
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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Related Material:
ON THE PLASTICITY OF SYNAPSES
The following points are made by M. Sur et al (Current Biology 2002 12:R168):
1) An important and difficult task in neuroscience is to integrate knowledge of the rules governing the behavior of single neurons studied in reduced systems into our understanding of the behaviors of networks of neurons in an intact brain. From work on reduced preparations, such as cultured neurons and brain slices, numerous forms of synaptic plasticity have been described and their properties characterized. In recent years, rules for changing synaptic efficacy based on the precise timing of presynaptic and postsynaptic activity, on the scale of tens of milliseconds, have been revealed at several synapses in the central nervous system (CNS). This spike-timing-dependent plasticity has several properties which are desirable, on theoretical grounds, for transforming changes in environmental inputs into changes in neural representations. The implementation of such a "learning rule" in functional neural circuits has been largely limited to theoretical work, because of the technical difficulty of observing and controlling synaptic activity in the intact brain at an adequate spatial and temporal resolution. Whether spike-timing-dependent plasticity is instantiated in vivo has been unclear, but recent studies [1,2] have demonstrated its role in the intact cortex using similar, but complementary, approaches.
2) Experiments in a number of systems have shown that the strength of synaptic transmission can be modified up or down depending on the precise timing of presynaptic and postsynaptic activity [3,4]. When presynaptic activity repeatedly precedes postsynaptic activity by 5-20 milliseconds, a synapse will undergo a long-lasting (approximately 30-60 minute) increase in strength; when the temporal order of pairing is reversed, a long-lasting depression of synaptic strength ensues. The functional consequence of this "learning rule" is that synapses from a presynaptic neuron which contribute to the firing of the postsynaptic neuron will be strengthened, whereas synapses which are uncorrelated or anti-paired with postsynaptic spike times will tend to be weakened. Such a rule for the modification of synaptic weights expands current thinking about "Hebbian rules" governing the development of sensory cortex and its plasticity in the mature brain (for an interesting computational analysis of how spike-timing-dependent rules can explain synaptic plasticity and cortical maps, see [5]).
3) The primary visual cortex (V1) of the mammalian brain has been a rich proving ground for work on the experience-dependent development and plasticity of functional cortical circuits. The responses of V1 neurons are selective for the orientation of lines presented in their receptive fields . V1 contains a map of orientation preference, such that neurons sharing the same orientation preference are grouped together, with the preferred orientation changing gradually across expanses of the cortex. This selectivity presumably arises from the specific arrangement of thalamic and cortical synaptic inputs a neuron receives. By selectively manipulating these inputs, either pharmacologically or by altering the visual inputs to developing or adult brains, one can change the selectivity of the responses of neurons and the structure of the orientation map.
4) In summary: Recent studies have tested whether synaptic learning rules, inferred earlier from work on cell cultures and brain slices, apply in intact brains. The evidence indicates that they do, and reveals interesting implications for brain development and perceptual learning.
References (abridged):
1. Schuett S., Bonhoeffer T. and Hubener M. (2001) Pairing-induced changes of orientation maps in cat visual cortex. Neuron, 32:325-337
2. Yao H. and Dan Y. (2001) Stimulus timing-dependent plasticity in cortical processing of orientation. Neuron, 32:315-323
3. Markram H., Lubke J., Frotscher M. and Sakmann B. (1997) Regulation of synaptic efficacy by coincidence of postsynaptic APs and EPSPs. Science, 275:213-215
4. Zhang L.I., Tao H.W., Holt C.E., Harris W.A. and Poo M. (1998) A critical window for cooperation and competition among developing retinotectal synapses. Nature, 395:37-44
5. Song S., Miller K.D. and Abbott L.F. (2000) Competitive Hebbian learning through spike-timing-dependent synaptic plasticity. Nat. Neurosci., 3:919-926
Current Biology http://www.current-biology.com
ScienceWeek http://scienceweek.com
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