Toward optogenetic control of neural synchrony : experimental results from the hippocampal slice model of gamma oscillations and computational modeling

[摘要] Ever since Hans Berger recorded the first human EEGs in humans and observed large, rhythmic 8 Hz field oscillations, neuroscientists have been intrigued by the pervasive presence of synchronized, regular patterns of the activity in the brain. A number of frequency bands, spanning from 0.1 to several hundred hertz have been described, and associated with particular functions and brain states. Not surprisingly, disruptions in such patterns have been postulated to be the mechanistic basis of a number of disorders, from schizophrenia to Parkinson;;s disease, to Alzheimer. Until now, however, virtually all evidence on the role of synchronous oscillations in brain functions has been merely correlative, that is, it has never been possible to selectively manipulate neural synchrony without altering other fundamental properties of the system and observing the functional outcome. This limit may now be overcome with the introduction of genetically targeted light-activeatable means of controlling neural activity, which allows spatially and temporally precise control of the activity of determined classes of neurons. Although the ultimate goal is to observe the functional, behavioral outcomes of modulating synchrony in awake animals, it;;s necessary first to develop such techniques in vitro, if we are to be able (given the current technological limitations) to extract useful ;;design principles;; that can meaningfully generalize. A particularly well-studied, reliable and yet relevant in vitro model, is the hippocampal slice gamma oscillations model, so we have been focusing on those as a testbed, integrating experimental work with computational modeling. Among the previously undescribed capabilities we have gained in the process are: precisely resetting the phase of an ongoing gamma oscillation, altering its frequency, and modulating its amplitude.

[发布机构] Massachusetts Institute of Technology