Parvalbumin neurons and gamma rhythms enhance cortical circuit performance

Gamma oscillations, synchronous activity rhythms in the neuronal network measured between 20 and 80 Hz, are active during information processing and attention, and are dysregulated in schizophrenia. What induces this activity band has been the subject of speculation and theory. Two papers in this issue report the use of cell-type-targeted optogenetic technologies to test the currently favoured theory — that these oscillations are generated by synchronous activity of fast-spiking (FS) interneurons, also known as parvalbumin-expressing interneurons. The results suggest that the theory is correct. Cardin et al. show that a gamma state can be driven by specific activation of FS interneurons in vivo, and that sensory input relative to these oscillations can determine the extent of evoked cortical activity. Sohal et al. report empirical evidence for the involvement of specific activation of FS interneurons in the production of gamma oscillations, and their data too suggest that gamma-based modulation of excitatory cells may enhance the signal-to-noise ratio in circuits. Interneurons defined by the fast-spiking phenotype and expression of the calcium-binding protein parvalbumin are thought to be involved in gamma oscillations. Here, optogenetic technology is used in mice to selectively modulate parvalbumin interneurons in vivo, revealing that inhibition of these interneurons suppresses gamma oscillations, whereas driving them is sufficient to generate emergent gamma-frequency rhythmicity. Synchronized oscillations and inhibitory interneurons have important and interconnected roles within cortical microcircuits. In particular, interneurons defined by the fast-spiking phenotype and expression of the calcium-binding protein parvalbumin1,2 have been suggested to be involved in gamma (30–80 Hz) oscillations3,4,5,6,7, which are hypothesized to enhance information processing8,9. However, because parvalbumin interneurons cannot be selectively controlled, definitive tests of their functional significance in gamma oscillations, and quantitative assessment of the impact of parvalbumin interneurons and gamma oscillations on cortical circuits, have been lacking despite potentially enormous significance (for example, abnormalities in parvalbumin interneurons may underlie altered gamma-frequency synchronization and cognition in schizophrenia10 and autism11). Here we use a panel of optogenetic technologies12,13,14 in mice to selectively modulate multiple distinct circuit elements in neocortex, alone or in combination. We find that inhibiting parvalbumin interneurons suppresses gamma oscillations in vivo, whereas driving these interneurons (even by means of non-rhythmic principal cell activity) is sufficient to generate emergent gamma-frequency rhythmicity. Moreover, gamma-frequency modulation of excitatory input in turn was found to enhance signal transmission in neocortex by reducing circuit noise and amplifying circuit signals, including inputs to parvalbumin interneurons. As demonstrated here, optogenetics opens the door to a new kind of informational analysis of brain function, permitting quantitative delineation of the functional significance of individual elements in the emergent operation and function of intact neural circuitry.