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Increased olfactory bulb acetylcholine bi-directionally modulates glomerular odor sensitivity.

Bendahmane M, Ogg MC, Ennis M, Fletcher ML - Sci Rep (2016)

Bottom Line: Overall, we found that ACh in the OB increases glomerular sensitivity to odors and decreases activation thresholds.This effect, along with the decreased responses to strong odor input, reduces the response intensity range of individual glomeruli to increasing concentration making them more similar across the entire concentration range.As a result, odor representations are more similar as concentration increases.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

ABSTRACT
The glomerular layer of the olfactory bulb (OB) receives heavy cholinergic input from the horizontal limb of the diagonal band of Broca (HDB) and expresses both muscarinic and nicotinic acetylcholine (ACh) receptors. However, the effects of ACh on OB glomerular odor responses remain unknown. Using calcium imaging in transgenic mice expressing the calcium indicator GCaMP2 in the mitral/tufted cells, we investigated the effect of ACh on the glomerular responses to increasing odor concentrations. Using HDB electrical stimulation and in vivo pharmacology, we find that increased OB ACh leads to dynamic, activity-dependent bi-directional modulation of glomerular odor response due to the combinatorial effects of both muscarinic and nicotinic activation. Using pharmacological manipulation to reveal the individual receptor type contributions, we find that m2 muscarinic receptor activation increases glomerular sensitivity to weak odor input whereas nicotinic receptor activation decreases sensitivity to strong input. Overall, we found that ACh in the OB increases glomerular sensitivity to odors and decreases activation thresholds. This effect, along with the decreased responses to strong odor input, reduces the response intensity range of individual glomeruli to increasing concentration making them more similar across the entire concentration range. As a result, odor representations are more similar as concentration increases.

No MeSH data available.


Related in: MedlinePlus

Neostigmine bidirectionally modulates glomerular odor responses.(A) 10× magnification images of responses to increasing concentrations of 2 heptanone in control condition (top) and during neostigmine (Neo) application (bottom). Glomerular odor responses are increased after neostigmine application for the low concentration, they remain unchanged at the middle range concentration and are decreased at the high concentration. (B) Fluorescence signal traces for the selected glomerulus shown in A showing response increase (for all the 0.05% concentration), no change (1.0%) or decrease (3%). (C) Example of a sigmoid fit of Log odor concentration- normalized odor responses curves in control and during neostigmine application. Neostigmine shifts the curve to the left resulting on decreasing the EC50 and also decreases the maximum response. (D) Sigmoid fit of Log odor concentration – normalized odor responses of all the glomeruli shown in A, the thick lines show the average curves in both control (black) and neostigmine (red) conditions. The grey and red curves are individual curves of each responsive glomerulus before and during neostigmine application. (E) Population normalized control and post-neostigmine curves, plotted as function of the normalized control responses divided into 10% intervals. The curves show that odor responses are increased by neostigmine from the [0–40%] intervals, are unchanged around 50% causing the post-neostigmine curve to cross the control curve at this point, and responses are significantly decreased in the [60–100%] intervals. *p < 0.01, ns: p > 0.05). Red bar: post-neostigmine responses are not significant from each other within the [30–80%[interval.
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f3: Neostigmine bidirectionally modulates glomerular odor responses.(A) 10× magnification images of responses to increasing concentrations of 2 heptanone in control condition (top) and during neostigmine (Neo) application (bottom). Glomerular odor responses are increased after neostigmine application for the low concentration, they remain unchanged at the middle range concentration and are decreased at the high concentration. (B) Fluorescence signal traces for the selected glomerulus shown in A showing response increase (for all the 0.05% concentration), no change (1.0%) or decrease (3%). (C) Example of a sigmoid fit of Log odor concentration- normalized odor responses curves in control and during neostigmine application. Neostigmine shifts the curve to the left resulting on decreasing the EC50 and also decreases the maximum response. (D) Sigmoid fit of Log odor concentration – normalized odor responses of all the glomeruli shown in A, the thick lines show the average curves in both control (black) and neostigmine (red) conditions. The grey and red curves are individual curves of each responsive glomerulus before and during neostigmine application. (E) Population normalized control and post-neostigmine curves, plotted as function of the normalized control responses divided into 10% intervals. The curves show that odor responses are increased by neostigmine from the [0–40%] intervals, are unchanged around 50% causing the post-neostigmine curve to cross the control curve at this point, and responses are significantly decreased in the [60–100%] intervals. *p < 0.01, ns: p > 0.05). Red bar: post-neostigmine responses are not significant from each other within the [30–80%[interval.

Mentions: The HDB contains both cholinergic and GABAergic neurons that project to multiple regions1. Therefore, it is possible that the HDBS-evoked effects on glomerular odor responses could be due to either ACh and/or GABA receptor activation. Moreover, an indirect effect of ACh release in other olfactory regions that provide centrifugal projections to the OB is also a possibility. To isolate OB cholinergic effects, we used OB bath application of the cholinesterase inhibitor neostigmine to specifically increase ACh. Cholinesterase blockers rapidly increase endogenous ACh levels31 and are known to have strong effects on odor discrimination and OB single neuron activity192122. In nine mice, we recorded glomerular odor responses from 197 glomeruli to different odors and concentrations before and after OB topical application of neostigmine. Similar to HDBS, neostigmine induced an absolute increase of 2.28 ± 0.04% ΔF/F in the glomerular odor-evoked responses compared to control trials (1095 pre-post neostigmine paired responses, paired t-test, t = 31.65, df = 1094, p < 0.001); Fig. 3A,B.


Increased olfactory bulb acetylcholine bi-directionally modulates glomerular odor sensitivity.

Bendahmane M, Ogg MC, Ennis M, Fletcher ML - Sci Rep (2016)

Neostigmine bidirectionally modulates glomerular odor responses.(A) 10× magnification images of responses to increasing concentrations of 2 heptanone in control condition (top) and during neostigmine (Neo) application (bottom). Glomerular odor responses are increased after neostigmine application for the low concentration, they remain unchanged at the middle range concentration and are decreased at the high concentration. (B) Fluorescence signal traces for the selected glomerulus shown in A showing response increase (for all the 0.05% concentration), no change (1.0%) or decrease (3%). (C) Example of a sigmoid fit of Log odor concentration- normalized odor responses curves in control and during neostigmine application. Neostigmine shifts the curve to the left resulting on decreasing the EC50 and also decreases the maximum response. (D) Sigmoid fit of Log odor concentration – normalized odor responses of all the glomeruli shown in A, the thick lines show the average curves in both control (black) and neostigmine (red) conditions. The grey and red curves are individual curves of each responsive glomerulus before and during neostigmine application. (E) Population normalized control and post-neostigmine curves, plotted as function of the normalized control responses divided into 10% intervals. The curves show that odor responses are increased by neostigmine from the [0–40%] intervals, are unchanged around 50% causing the post-neostigmine curve to cross the control curve at this point, and responses are significantly decreased in the [60–100%] intervals. *p < 0.01, ns: p > 0.05). Red bar: post-neostigmine responses are not significant from each other within the [30–80%[interval.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4863144&req=5

f3: Neostigmine bidirectionally modulates glomerular odor responses.(A) 10× magnification images of responses to increasing concentrations of 2 heptanone in control condition (top) and during neostigmine (Neo) application (bottom). Glomerular odor responses are increased after neostigmine application for the low concentration, they remain unchanged at the middle range concentration and are decreased at the high concentration. (B) Fluorescence signal traces for the selected glomerulus shown in A showing response increase (for all the 0.05% concentration), no change (1.0%) or decrease (3%). (C) Example of a sigmoid fit of Log odor concentration- normalized odor responses curves in control and during neostigmine application. Neostigmine shifts the curve to the left resulting on decreasing the EC50 and also decreases the maximum response. (D) Sigmoid fit of Log odor concentration – normalized odor responses of all the glomeruli shown in A, the thick lines show the average curves in both control (black) and neostigmine (red) conditions. The grey and red curves are individual curves of each responsive glomerulus before and during neostigmine application. (E) Population normalized control and post-neostigmine curves, plotted as function of the normalized control responses divided into 10% intervals. The curves show that odor responses are increased by neostigmine from the [0–40%] intervals, are unchanged around 50% causing the post-neostigmine curve to cross the control curve at this point, and responses are significantly decreased in the [60–100%] intervals. *p < 0.01, ns: p > 0.05). Red bar: post-neostigmine responses are not significant from each other within the [30–80%[interval.
Mentions: The HDB contains both cholinergic and GABAergic neurons that project to multiple regions1. Therefore, it is possible that the HDBS-evoked effects on glomerular odor responses could be due to either ACh and/or GABA receptor activation. Moreover, an indirect effect of ACh release in other olfactory regions that provide centrifugal projections to the OB is also a possibility. To isolate OB cholinergic effects, we used OB bath application of the cholinesterase inhibitor neostigmine to specifically increase ACh. Cholinesterase blockers rapidly increase endogenous ACh levels31 and are known to have strong effects on odor discrimination and OB single neuron activity192122. In nine mice, we recorded glomerular odor responses from 197 glomeruli to different odors and concentrations before and after OB topical application of neostigmine. Similar to HDBS, neostigmine induced an absolute increase of 2.28 ± 0.04% ΔF/F in the glomerular odor-evoked responses compared to control trials (1095 pre-post neostigmine paired responses, paired t-test, t = 31.65, df = 1094, p < 0.001); Fig. 3A,B.

Bottom Line: Overall, we found that ACh in the OB increases glomerular sensitivity to odors and decreases activation thresholds.This effect, along with the decreased responses to strong odor input, reduces the response intensity range of individual glomeruli to increasing concentration making them more similar across the entire concentration range.As a result, odor representations are more similar as concentration increases.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

ABSTRACT
The glomerular layer of the olfactory bulb (OB) receives heavy cholinergic input from the horizontal limb of the diagonal band of Broca (HDB) and expresses both muscarinic and nicotinic acetylcholine (ACh) receptors. However, the effects of ACh on OB glomerular odor responses remain unknown. Using calcium imaging in transgenic mice expressing the calcium indicator GCaMP2 in the mitral/tufted cells, we investigated the effect of ACh on the glomerular responses to increasing odor concentrations. Using HDB electrical stimulation and in vivo pharmacology, we find that increased OB ACh leads to dynamic, activity-dependent bi-directional modulation of glomerular odor response due to the combinatorial effects of both muscarinic and nicotinic activation. Using pharmacological manipulation to reveal the individual receptor type contributions, we find that m2 muscarinic receptor activation increases glomerular sensitivity to weak odor input whereas nicotinic receptor activation decreases sensitivity to strong input. Overall, we found that ACh in the OB increases glomerular sensitivity to odors and decreases activation thresholds. This effect, along with the decreased responses to strong odor input, reduces the response intensity range of individual glomeruli to increasing concentration making them more similar across the entire concentration range. As a result, odor representations are more similar as concentration increases.

No MeSH data available.


Related in: MedlinePlus