Broad activation of the olfactory bulb produces long-lasting changes in odor perception

Abstract

A number of electrophysiological experiments have shown that odor exposure alone, unaccompanied by behavioral training, changes the response patterns of neurons in the olfactory bulb. As a consequence of these changes, across mitral cells in the olfactory bulb, individual odors should be better discriminated because of previous exposure. We have previously shown that a daily 2-h exposure to odorants during 2 weeks enhances rats' ability to discriminate between chemically similar odorants. Here, we first show that the perception of test odorants is only modulated by enrichment with odorants that activate at least partially overlapping regions of the olfactory bulb. Second, we show that a broad activation of olfactory bulb neurons by daily local infusion of NMDA into both olfactory bulbs enhances the discrimination between chemically related odorants in a manner similar to the effect of daily exposure to odorants. Computational modeling of the olfactory bulb suggests that activity-dependent plasticity in the olfactory bulb can support the observed modulation in olfactory discrimination capability by enhancing contrast and synchronization in the olfactory bulb. Last, we show that blockade of NMDA receptors in the olfactory bulb impairs the effects of daily enrichment, suggesting that NMDA-dependent plasticity is involved in the changes in olfactory processing observed here.

Fig. 1.

Perception of odorants is only modulated by enrichment with odorants that activate at least partially overlapping regions of the OB. (A) Time course of the experiment. (B) Maps of 2-dexoxyglucose (2-DG) uptake across the entire glomerular layer in rats exposed to + lim, pent, and dec. Overlaps between + lim and pent (pairwise correlation coefficient, r = 0.28) are more important than overlaps between + lim and dec (pairwise correlation coefficient, r = −0.06). Courtesy of B. Johnson and M. Leon (http://leonlab.bio.uci.edu). (C) Behavioral habituation and discrimination before (Ci) and after (Cii) enrichment. The two enantiomers of lim are confused before the enrichment period, whereas after enrichment with +/− lim or pent/but, they are discriminated. Enrichment with dec/dodec has the same effect as no odor, indicating that the discrimination is improved when the enrichment is done with a partially overlapped odor. Asterisks indicate a significant difference (P < 0.05) in response magnitude between trials 4 and 5.

Fig. 2.

Effect of nonspecific activation of the OB using local infusions of NMDA. (A) The two enantiomers of lim (Ai) and terp (Aii) were not discriminated before enrichment. (B) After the enrichment period, both groups discriminated +/− lim (Bi) and +/− terp (Bii).

Fig. 3.

Computational modeling. (A) Schematic illustration of the OB model. A total of 50 OSNs, each representing the population response of OSNs with similar odorant-binding affinities, each project to a single glomerulus in which they make excitatory synapses onto mitral cells and periglomerular cells. Each mitral cell represents the average activity of the 10–15 mitral cells with primary dendrites in a given glomerulus. Mitral and periglomerular cells have reciprocal dendrodendritic synaptic interactions in which mitral cells are excitatory and periglomerular cells are inhibitory. In addition to these interglomerular interactions, periglomerular cells also interact with mitral cells in a small (three to four) number of surrounding glomeruli. Mitral cell secondary dendrites excite granule cells in a wide area of the model, and each mitral cell forms excitatory synaptic connections with ≈50% of the model granule cells. Granule cells in turn inhibit mitral cells via dendrodendritic inhibitory synapses. Modifiable excitatory synapses (arrows) were implemented between OSNs and mitral cells as well as between mitral and granule cells, as described in refs. –. During activity-induced plasticity, the synaptic strengths of these synapses were updated by means of a classical hebbian learning rule in which the change in synaptic strength depends on pre- and postsynaptic activity (see Methods for details). (B) Because each mitral cell (black triangle) excites a large number of granule cells in the model (black circles), odor activation of a single mitral cell spreads activation to a large fraction of granule cells, leading to changes in odor processing that affect mitral cell activation by other odorants. (C) Simulated odorants. In the model, all odorants activate a subset (25–30%) of OSNs to various degrees. Odorants were chosen in such a manner that the OSN patterns overlapped to the same degree as experimental odorants (see Fig. 1B). The graph shows the average activation of each glomerulus during the time of stimulus application in response to the six odorants used in the simulations. For ease of comparison, each pair of test odorants is shown on a separate axis. For comparison with experimental data from Fig. 1, the correlation values between odor A1, B1, and C1 are given on this graph.

Fig. 4.

Simulation results. (A) Average mitral cell activation (numbers of action potentials fired during the time of odor application) across all 50 glomeruli in response to odors A1 and A2 are depicted before (pre) and after (post) activity-induced synaptic plasticity in response to odorants A1 + A2. One can see that the overlap between average mitral cell responses is reduced after the plasticity period. (B) Results from simulated olfactory enrichment experiments. The graphs show the average overlap (normalized scalar product) between network responses to odors A1 and A2 (representing +/− lim) before and after enrichment with A1 + A2 (+/− lim-enriched), B1 + B2 (but/pent-enriched), and C1 + C2 (dec/dodec-enriched). Each graph shows the average and standard deviation of 50 independent simulations. The overlap between responses to odors A1 and A2 is significantly decreased after a plasticity phase in response to odorants A1 + A2 or B1 + B2 but not C1 + C2. (C) Mitral cell responses to odorants are shown as a function of time. The subset of mitral cells responding to odors A1, B1, and C1 are shown. The network was first stimulated with odors A1, B1, and C1 for 100 ms each. It was then submitted to a phase of synaptic plasticity mimicking daily odor exposure with odors A1 and A2. Subsequently, the network was again activated with odors A1, B1, and C1 for 100 ms each. Because of the modulation of OB synapses in response to odorants A1 and A2, both the oscillatory response and the mitral cell responses to odorants A1 and B1, but not C1, are changed.

Fig. 5.

Blockade of NMDA receptors before daily odor exposure blocks the effect of enrichment on odor discrimination. (A) Preenrichment. In these graphs, results from a group of rats in which MK-801 was injected before the daily odor exposure to +/− lim are shown. The two enantiomers of lim (Ai) and terp (Aii) were not discriminated before enrichment. (B) Postenrichment. After the enrichment period, rats could not discriminate between the enantiomers of lim (Bi) or terp (Bii), showing that blockade of OB NMDA receptors blocks the effects of daily odor exposure. (C) OB blockade of NMDA receptors with MK-801 at the concentrations used in these experiments does not impair the detection of lim and terp. Saline-injected control rats and MK-801-injected rats were first habituated to mineral oil during four trials and then exposed to either lim or terp during the fifth trial. Both groups of rats responded significantly more to the test odor during the last trial than to the mineral oil in the previous trial.