Parvalbumin neurons and gamma rhythms enhance cortical circuit performance

Abstract

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) oscillations3–7, 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 technologies12–14 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.

Dysconnectivity, large-scale networks and neuronal dynamics in schizophrenia

“…Much work has been devoted to the analysis of synaptic mechanisms and circuits that support the generation of oscillatory activity and its synchronization over short and long distances [20], respectively, which makes it possible to relate abnormalities of these dynamic phenomena to specific neuronal processes [21]. In particular, experimental and theoretical evidence indicates that the networks of mutually interacting GABAergic neurons are crucially involved as pacemakers in the generation of high-frequency oscillations in local circuits [22,23]. Recent studies have also examined the specific role of glutamatergic inputs to PVinterneurons for the generation of coordinated network-activity.…”

Does schizophrenia arise from oxidative dysregulation of parvalbumin-interneurons in the developing cortex?

“…In particular, synaptic inhibition from PVinterneurons controls the firing rates of pyramidal neurons, synchronizes spikes within populations of neurons, and participates in the development of executive functions associated with prefrontal brain regions (Kawaguchi and Kubota, 1993;Goldman-Rakic, 1999;Markram et al, 2004). PV-interneurons are a part of the network that generates oscillatory activity in the gamma range (Sohal et al, 2009;Cardin et al, 2009), suggesting that their dysfunction may account for the disruption in evoked gamma-frequency oscillations and as well as the cognitive deficits observed in schizophrenia (GonzalezBurgos and Lewis, 2008;Roopun et al, 2008;Uhlhaas et al, 2008).…”

Selective Manipulation of Neural Circuits

“…In the flip-excision system, the transgene is encoded reversed and double-floxed between loxP sites, rendering it unable to be expressed [47,48]. However, in the presence of Cre, the transgene is flipped into the sense orientation and permanently expressed [48,49].…”