Finally, the role of γ rhythms in sensory coding is still debated, notably because of the lack of experimental means to selectively manipulate γ synchronization in awake rodents. Here, we combine genetic, optogenetic, and pharmacological tools with in vivo electrophysiology in the awake mouse and identify the neuronal circuit necessary to generate γ oscillations in the OB. Using multielectrode recordings, we show that a moderate increase in the excitation/inhibition balance of output neurons increases their long-range γ synchronization without altering their firing

rate or the inhibitory amplitude that they receive. Finally, we evaluate how such excitation/inhibition manipulations may affect odor discrimination and learning. The dendrodendritic reciprocal synapse mediates recurrent inhibition triggered by activation of NMDARs expressed on GC spines, with minimal effects from AMPARs (Isaacson see more and Strowbridge, 1998 and Chen et al., 2000; Figure 1A). To investigate its role in the generation of γ oscillations, we monitored local field potentials (LFPs) in the OB during spontaneous exploration after local microinfusion of NMDAR antagonists. LFP signals were composed of bursts of γ oscillations (40–100 Hz) superimposed

onto prominent slower oscillations in the theta range (1–10 Hz; Figure 1B). The theta oscillations are largely driven by sensory inputs (Margrie and Schaefer, 2003) and highly correlate AZD6244 supplier with the breathing rhythm (Figure S1A available online). Consequently, the power spectrum of the LFP exhibited peaks in two frequency bands, in the theta and in the γ range (Figure 1C). A local injection of an NMDAR antagonist (APV or MK801) induced a rapid and dose-dependent reduction in γ oscillation power (Figures

1B–1E), supporting the critical role of NMDAR in enabling γ oscillations. γ oscillations could be split in two subbands, the low (40–70 Hz) and high (70–100 Hz) bands. NMDAR antagonists disrupted both γ subbands (Figures 1B and 1C) without changing the mean γ frequency (Figures 1C and 1E). In contrast, NMDAR antagonists did not alter theta oscillations (APV 1 mM: +16.1% ± 13.5% of baseline theta power, p > 0.25, with a paired t test, n = 12; MK801 1 mM: +7.5% ± 10.3%, p > 0.25, n = 12). Gap junction coupling ifoxetine between interneurons can generate and maintain γ oscillations in the cortex (Whittington et al., 2011). However, infusion of the gap-junction blocker carbenoxolone (CBX, 25 mM) in the OB revealed that gap junctions did not contribute substantially to γ oscillations (Figure 1E). In contrast to NMDAR antagonists, injection of an AMPAR antagonist (NBQX, 0.2 mM) dramatically decreased both γ (−92.6% ± 1.4% of baseline γ power, p < 0.001, with a paired t test, n = 9) and theta (NBQX 0.2 mM: −68.1% ± 8.1% of baseline power, p < 0.01, paired t test, n = 9; data not shown) power.