光遗传技术比较好的一篇nature综述_精品文档.pdf

1、298VOLUME 15|NUMBER 2|FEBRUARY 2012 nature neurOSCIenCeartICleSRetinal ganglion cell(RGC)projections to the brain form stereo-typic maps for eye of origin and retinotopic location,making them an ideal model system to study the development and plasticity of precisely patterned neural circuits1,2.The

2、initial formation of these visual circuits is thought to be guided by molecular cues3,whereas the refinement and maintenance46 of these connections seems to be activity dependent7.Substantial evidence supports a general role for activity-dependent binocular competition in retinofugal map devel-opmen

3、t.For instance,a relative increase in activity in one eye leads to the expansion of that eyes target territory in the dorsal lateral genicu-late nucleus(dLGN)8,9,indicating that the more active eye makes and further strengthens more target synapses when it is at a competi-tive advantage.Hebbian syna

4、ptic learning rules that may mediate the activity-dependent development of visual maps have been observed in a variety of retinofugal systems,including spike-timing dependent plasticity at retinotectal synapses in tadpoles in vivo10 and burst timingdependent plasticity at retinogeniculate11 and reti

5、nocollicular12 synapses in rodents in vitro.These observations suggest that synaptic connections are functionally strengthened when cells are synchronously active and weakened when cells are asynchronously active over time windows that are distinct in different model systems13.It has long been postu

6、lated that the timing of spontaneous wave-like activity in RGCs14 is critical for the establishment and maintenance of eye-specific segregation through a Hebb-based synaptic learning rule11,13 before the onset of vision.The short duration of retinal waves relative to the interval between waves is th

7、ought to asynchronously activate the two eyes,resulting in the refinement of eye-specific domains15.Evidence for this timing model for binocular competition is limited,with the only direct experimental support coming from classic cat experiments in which artificially asynchronous stimulation of the

8、optic nerves produced neurons that responded predominantly to only one eye,whereas stimulation of the optic tract,which synchro-nously activates RGC afferents from both eyes,caused most cells in visual cortex to become functionally binocular16.Similarly,alternat-ing monocular occlusion in cats resul

9、ts in reduced cortical binocular-ity and disrupted depth discrimination17.However,these experiments were restricted to a physiological analysis of binocularity in the cortex and manipulated RGC activity after the onset of normal visual experi-ence,when eye segregation in the dLGN and visual cortex h

10、as already emerged2,18.Because it has been difficult to precisely manipulate neo-natal RGC activity in mammals in vivo,the role of timing in the initial development of visual maps remains unexplored.We chronically manipulated retinal activity in mice before the onset of vision over a range of time s

11、cales in vivo by expressing the light-gated cation channel Channelrhodopsin-2(ChR2)19 directly in RGCs using transgenic and viral transfection methods20,21.Light-driven activation of ChR2-expressing RGCs triggered precisely timed post-synaptic calcium signals in the superior colliculus,demonstrating

12、 that optogenetic techniques can reliably drive neuronal response even early in visual development.When the two eyes were synchronously stimu-lated,we found that the initial emergence of eye-specific domains was disrupted,whereas asynchronous stimulation improved segregation.After eye-specific domai

13、ns were already established in the superior colliculus and dLGN,asynchronous stimulation had no effect,but syn-chronous stimulation caused domains to desegregate.The disruptive effect of optogenetic stimulation on eye segregation waned as the time difference between stimulation of the eyes increased

14、 beyond 100 ms,which suggests a sub-second time window for binocular competi-tion.Of note,when synchronous stimulation disrupted eye-specific 1Department of Neurobiology,Yale University,New Haven,Connecticut,USA.2Department of Ophthalmology&Visual Sciences,Yale University,New Haven,Connecticut,USA.C

15、orrespondence should be addressed to M.C.C.(michael.crairyale.edu).Received 8 September;accepted 9 November;published online 18 December 2011;doi:10.1038/nn.3007Visual map development depends on the temporal pattern of binocular activity in miceJiayi Zhang1,James B Ackman1,Hong-Ping Xu1&Michael C Cr

16、air1,2Binocular competition is thought to drive eye-specific segregation in the developing visual system,potentially through Hebbian synaptic learning rules that are sensitive to correlations in afferent activity.Altering retinal activity can disrupt eye-specific segregation,but little is known about the temporal features of binocular activity that modulate visual map development.We used optogenetic techniques to directly manipulate retinal activity in vivo and identified a critical period befor