CRE-mediated gene transcription in neocortical neuronal plasticity during the developmental critical period.
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Neuronal activity-dependent processes are believed to mediate the formation of synaptic connections during neocortical development, but the underlying intracellular mechanisms are not known. In the visual system, altering the pattern of visually driven neuronal activity by monocular deprivation induces cortical synaptic rearrangement during a postnatal developmental window, the critical period. Here, using transgenic mice carrying a CRE-lacZ reporter, we demonstrate that a calcium- and cAMP-regulated signaling pathway is activated following monocular deprivation. We find that monocular deprivation leads to an induction of CRE-mediated lacZ expression in the visual cortex preceding the onset of physiologic plasticity, and this induction is dramatically downregulated following the end of the critical period. These results suggest that CRE-dependent coordinate regulation of a network of genes may control physiologic plasticity during postnatal neocortical development. (+info)
Early visual experience shapes the representation of auditory space in the forebrain gaze fields of the barn owl.
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Auditory spatial information is processed in parallel forebrain and midbrain pathways. Sensory experience early in life has been shown to exert a powerful influence on the representation of auditory space in the midbrain space-processing pathway. The goal of this study was to determine whether early experience also shapes the representation of auditory space in the forebrain. Owls were raised wearing prismatic spectacles that shifted the visual field in the horizontal plane. This manipulation altered the relationship between interaural time differences (ITDs), the principal cue used for azimuthal localization, and locations of auditory stimuli in the visual field. Extracellular recordings were used to characterize ITD tuning in the auditory archistriatum (AAr), a subdivision of the forebrain gaze fields, in normal and prism-reared owls. Prism rearing altered the representation of ITD in the AAr. In prism-reared owls, unit tuning for ITD was shifted in the adaptive direction, according to the direction of the optical displacement imposed by the spectacles. Changes in ITD tuning involved the acquisition of unit responses to adaptive ITD values and, to a lesser extent, the elimination of responses to nonadaptive (previously normal) ITD values. Shifts in ITD tuning in the AAr were similar to shifts in ITD tuning observed in the optic tectum of the same owls. This experience-based adjustment of binaural tuning in the AAr helps to maintain mutual registry between the forebrain and midbrain representations of auditory space and may help to ensure consistent behavioral responses to auditory stimuli. (+info)
Selective pruning of more active afferents when cat visual cortex is pharmacologically inhibited.
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Activity-dependent competition is thought to guide the normal development of specific patterns of neural connections. Such competition generally favors more active inputs, making them larger and stronger, while less active inputs become smaller and weaker. We pharmacologically inhibited the activity of visual cortical cells and measured the three-dimensional structure of inputs serving the two eyes when one eye was occluded. The more active inputs serving the open eye actually became smaller than the deprived inputs from the occluded eye, which were similar to those in normal animals. These findings demonstrate in vivo that it is not the amount of afferent activity but the correlation between cortical and afferent activity that regulates the growth or retraction of these inputs. (+info)
The physiological effects of monocular deprivation and their reversal in the monkey's visual cortex.
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1. 1127 single units were recorded during oblique penetrations in area 17 of one normal, three monocularly deprived and four reverse sutured monkeys. 2. In all animals most cells outside layer IV c were orientation-selective, and preferred orientation usually shifted from cell to cell in a regular progressive sequence. 3. The presence in layer IV c of non-oriented, monocularly driven units, organized in alternating right-eye and left-eye 'stripes' (LeVay, Hubel & Wiesel, 1975) was confirmed. 4. Early monocular deprivation (2--5 1/2 weeks) caused a strong shift of ocular dominance towards the non-deprived eye. However, even outside layer IV c, neural background and some isolated cells could still be driven from the deprived eye in regularly spaced, narrow columnar regions. In layer IV c the non-deprived eye's stripes were almost three times wider, on average, than the deprived. 5. Later monocular deprivation (11--16 months) had no detectable influence on layer IV c but seemed to cause a small shift in ocular dominance outside IV c. Deprivation for 6 1/4 months in an adult had no such effect. 6. After early reverse suturing (at 5 1/2 weeks) the originally deprived eye gained dominance over cells outside layer IV c just as complete as that originally exercised by the eye that was first non-deprived. 7. The later reverse suturing was delayed, the less effective was recapture by the originally deprived eye. Reversal at 8 weeks led to roughly equal numbers of cells being dominated by each eye; fewer cells became dominated by the newly open eye after reverse suturing at 9 weeks and most of them were non-oriented; reversal at 38 1/2 weeks had no effect. 8. Binocular cells, though rare in reverse sutured animals, always had very similar preferred orientations in the two eyes. The columnar sequences of preferred orientation were not interrupted at the borders of ocular dominance columns. 9. Even within layer IV c there was evidence for re-expansion of physiologically determined ocular dominance stripes. After early reverse suture, stripes for the two eyes became roughly equal in width. Possible mechanisms for these changes are discussed. (+info)
Regulation of the mechanical properties of tree shrew sclera by the visual environment.
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Experiments in several species have shown that the axial elongation rate of the developing eye can be increased or decreased by manipulating the visual environment, indicating that a visually guided emmetropization mechanism controls the enlargement of the vertebrate eye during postnatal development. Previous studies in tree shrews (Tupaia glis belangeri) suggest that regulation of the mechanical properties of the sclera may be an important part of the mechanism that controls the axial elongation rate in this mammal. To learn whether the mechanical properties of the sclera change when the axial elongation rate is increased or decreased under visual control, uniaxial mechanical tests were performed on 3-mm wide strips of tree shrew sclera. The creep rate was measured under 1, 3, and 5 g of tension, maintained for 30 min at each level. The modulus of elasticity was calculated from the elastic extension that occurred when the force was increased from 0 to 1 g, 1 to 3 g, and 3 to 5 g. Both were measured in the sclera of both eyes from animals exposed to four experimental conditions: (1) Normal development, at intervals from the day of natural eyelid opening (day 1 of visual experience [VE]) to greater than 5 years of age; (2) Monocular form deprivation (MD), for varying lengths of time; (3) Recovery from MD; (4) Monocular -5 D lens treatment. The creep rate was low in normal animals (1-2% elongation/h), did not change significantly between day 1 and day 75 of VE, and was not significantly different between the two eyes. Four days of MD produced a 200-300% increase in creep rate in the sclera from deprived eyes. Creep rate remained similarly elevated after 11 and 21 days of MD. After 2 days of recovery, which followed 11 days of MD, the creep rate of sclera from the recovering eyes was below normal levels. In animals that wore a monocular -5 D lens for up to 21 days, creep rate increased, and then decreased, in concert with the increase, and decrease, in axial elongation rate as the eyes compensated for the lens. The modulus of elasticity of the sclera was not significantly affected by any manipulation. The temporal correspondence between changes in axial elongation rate and changes in creep rate support the hypothesis that regulation of the time-dependent mechanical properties of fibrous mammalian sclera plays a role in controlling axial elongation rate during both normal emmetropization and the development of refractive errors. (+info)
Anatomical correlates of functional plasticity in mouse visual cortex.
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Much of what is known about activity-dependent plasticity comes from studies of the primary visual cortex and its inputs in higher mammals, but the molecular bases remain largely unknown. Similar functional plasticity takes place during a critical period in the visual cortex of the mouse, an animal in which genetic experiments can readily be performed to investigate the underlying molecular and cellular events. The experiments of this paper were directed toward understanding whether anatomical changes accompany functional plasticity in the developing visual cortex of the mouse, as they do in higher mammals. In normal mice, transneuronal label after an eye injection clearly delineated the monocular and binocular zones of area 17. Intrinsic signal optical imaging also showed monocular and binocular zones of area 17 but revealed no finer organization of ocular dominance or orientation selectivity. In normal animals, single geniculocortical afferents serving the contralateral eye showed great heterogeneity and no clustering consistent with the presence of ocular dominance patches. Growth and elaboration of terminal arbor continues beyond postnatal day 40 (P40), after the peak of the critical period. After prolonged monocular deprivation (MD) from P20 to P60, transneuronal labeling showed that the projection serving the ipsilateral eye was severely affected, whereas the effect on the contralateral eye's pathway was inconsistent. Optical imaging also showed profound effects of deprivation, particularly in the ipsilateral pathway, and microelectrode studies confirmed continued functional plasticity past P40. Reconstruction of single afferents showed that MD from P20 to P40 promoted the growth of the open eye's geniculocortical connections without causing the closed eye's contralateral projection to shrink, whereas MD from P20 to P60 caused an arrest of growth of deprived arbors. Our findings reveal numerous similarities between mouse and higher mammals in development and plasticity, along with some differences. We discuss the factors that may be responsible for these differences. (+info)
Path integration absent in scent-tracking fimbria-fornix rats: evidence for hippocampal involvement in "sense of direction" and "sense of distance" using self-movement cues.
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Allothetic and idiothetic navigation strategies use very different cue constellations and computational processes. Allothetic navigation requires the use of the relationships between relatively stable external (visual, olfactory, auditory) cues, whereas idiothetic navigation requires the integration of cues generated by self-movement and/or efferent copy of movement commands. The flexibility with which animals can switch between these strategies and the neural structures that support these strategies are not well understood. By capitalizing on the proclivity of foraging rats to carry large food pellets back to a refuge for eating, the present study examined the contribution of the hippocampus to the use of allothetic versus idiothetic navigation strategies. Control rats and fimbria-fornix-ablated rats were trained to follow linear, polygonal, and octagonal scent trails that led to a piece of food. The ability of the rats to return to the refuge with the food via the shortest route using allothetic cues (visual cues and/or the odor trail available) or using ideothetic cues (the odor trail removed and the rats blindfolded or tested in infrared light) was examined. Control rats "closed the polygon" by returning directly home in all cue conditions. Fimbria-fornix rats successfully used allothetic cues (closed the polygon using visual cues or tracked back on the string) but were insensitive to the direction and distance of the refuge and were lost when restricted to idiothetic cues. The results support the hypothesis that the hippocampal formation is necessary for navigation requiring the integration of idiothetic cues. (+info)
The growing eye: an autofocus system that works on very poor images.
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It is unknown which retinal image features are analyzed to control axial eye growth and refractive development. On the other hand, identification of these features is fundamental for the understanding of visually acquired refractive errors. Cyclopleged chicks were individually kept in the center of a drum with only one viewing distance possible. Defocusing spectacle lenses were used to stimulate the retina with defined defocus of similar magnitude but different sign. If spatial frequency content and contrast were the only cues analyzed by the retina, all chicks should have become myopic. However, compensatory eye growth was still always in the right direction. The most likely cues for emmetropization, spatial frequency content and image contrast, do therefore not correlate with the elongation of the eye. Rather, the sign of defocus was extracted even from very poor images. (+info)