Glomerulus-Specific, Long-Latency Activity in the Olfactory Bulb Granule Cell Network

Abstract

Reliable, stimulus-specific temporal patterns of action potentials have been proposed to encode information in many brain areas, perhaps most notably in the olfactory system. Analysis of such temporal coding has focused almost exclusively on excitatory neurons. Thus, the role of networks of inhibitory interneurons in establishing and maintaining this reliability is unclear. Here we use imaging of population activity in vitro to investigate the mechanisms of temporal pattern generation in mouse olfactory bulb inhibitory interneurons. We show that activity of these interneurons evolves slowly in time but that individual neurons fire at reliable times, with a timescale similar to the slow changes in the patterns of odor-evoked activity and to odor discrimination. Most strikingly, the latency of a single granule cell is highly reliable from trial to trial during repeated stimulation of the same glomerulus, whereas this same cell will have a markedly different latency when a different glomerulus is activated. These data suggest that the timing of granule cell-mediated inhibition in the olfactory bulb is tightly regulated by the source of input and that inhibition may contribute to the generation of reliable temporal patterns of mitral cell activity.

Activity-dependent gating of lateral inhibition in the mouse olfactory bulb

“…We found that changing the action potential train from one with uniform intervals (8 spikes at 40 ms) to one in which spikes were clustered (4 pairs of spikes at 40 ms) had no effect on the magnitude of granule cell-mediated recurrent inhibition (P > 0.8, n = 5). The lack of sensitivity to temporal coincidence of input in granule cells is consistent with the observation that they respond at long latencies 26 and are best activated by prolonged inputs 30 (see Discussion).…”

“…Previously, we have shown that granule cell calcium transients observed under these conditions are correlated with granule cell spiking 26 .…”

“…We next wanted to determine how mitral cell spike-timing was altered by lateral inhibition, given that results indicate the importance of spike timing and inhibition in olfactory processing in the bulb 3,[24][25][26] . To accomplish this, we computed the difference in the time-dependent firing rate from our paired recordings between trials with and without presynaptic mitral-cell activity.…”

“…Slices were visualized for successful loading using excitation 26 . A cooled back-illuminated frame transfer CCD camera (Micromax 512 BFT, Princeton Instruments) was used to capture sequences of images with exposure times of 25-50 ms per frame at 3 × 3 binning (final image size, 170 × 170 pixels).…”

Timescale-dependent shaping of correlation by olfactory bulb lateral inhibition

“…Such inputs have been observed from GABAergic granule cells (6,16,18) and may synchronize mitral cell firing via a mechanism dubbed "stochastic synchronization" (14). Second, we hypothesized that slow decorrelation arose from long latency, competitive recruitment of these same granule cells (11,12,42,43), giving rise to lateral inhibition whereby more active cells suppress firing of less active cells (11). We predicted that our experimental results might be explained by these known features of olfactory bulb inhibition.…”