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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

Functional implications of HDBS on unitary and population glomerular odor coding.(A) Log concentration–response curves in control and HDBS conditions. Odor responses are normalized to every condition’s maximum response. Log EC10, 50 and 90 are determined by the projection on the x axis of the crossing point of the curves with the blue (y = 0.1) grey (y = 0.5) and the green (y = 0.9) lines respectively. Log EC10 and 50 are shifted to the left by HDBS (red) compared to control (black), while Log EC90 is similar for both conditions. (B) Average Log EC10, 50 and 90 in control and HDBS conditions. HDBS significantly decreases Log EC10 by 0.93 Log unit and Log EC50 by 0.5 Log unit while not affecting EC90. (C) Responses of the dorsal OB (4× magnification) surface to 0.1% methyl valerate in control and HDBS conditions. HDBS increases the odor responses of the glomeruli activated in control condition and induced odor responses in additional glomeruli (dashed circles) that did not respond in the control condition. (D) Average mean response of the glomeruli that showed below threshold relative ΔF/F. HDBS increases the mean ΔF/F of these glomeruli from 5.2 ± 0.5% in control condition to 39.7 ± 4.9% after HDBS. (E) Log concentration–response curves in control and HDBS conditions for the same glomerulus as in A. Odor responses are normalized to control maximum response. Normalized responses to the Log concentrations EC10 and 90 were compared in both control and HDBS conditions, determined by the projection of the y axis of the crossing point of the curves with the lines x = control EC10 and x = control EC90 respectively. The distance between the Log EC10 and Log EC90 responses is smaller in HDBS condition [0.29–0.79] than in control condition [10–90]. (F) Graphic representation of the projections of minimum (circles) and maximum (squares) concentration on the principal component analysis on PC1 for the six selected animals. The distance from minimum to maximum is bigger in control condition (black) than with HDBS (red). (G) Mean PC1 minimum to maximum distances decreased by HDBS (n = 6), *p < 0.01.
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f6: Functional implications of HDBS on unitary and population glomerular odor coding.(A) Log concentration–response curves in control and HDBS conditions. Odor responses are normalized to every condition’s maximum response. Log EC10, 50 and 90 are determined by the projection on the x axis of the crossing point of the curves with the blue (y = 0.1) grey (y = 0.5) and the green (y = 0.9) lines respectively. Log EC10 and 50 are shifted to the left by HDBS (red) compared to control (black), while Log EC90 is similar for both conditions. (B) Average Log EC10, 50 and 90 in control and HDBS conditions. HDBS significantly decreases Log EC10 by 0.93 Log unit and Log EC50 by 0.5 Log unit while not affecting EC90. (C) Responses of the dorsal OB (4× magnification) surface to 0.1% methyl valerate in control and HDBS conditions. HDBS increases the odor responses of the glomeruli activated in control condition and induced odor responses in additional glomeruli (dashed circles) that did not respond in the control condition. (D) Average mean response of the glomeruli that showed below threshold relative ΔF/F. HDBS increases the mean ΔF/F of these glomeruli from 5.2 ± 0.5% in control condition to 39.7 ± 4.9% after HDBS. (E) Log concentration–response curves in control and HDBS conditions for the same glomerulus as in A. Odor responses are normalized to control maximum response. Normalized responses to the Log concentrations EC10 and 90 were compared in both control and HDBS conditions, determined by the projection of the y axis of the crossing point of the curves with the lines x = control EC10 and x = control EC90 respectively. The distance between the Log EC10 and Log EC90 responses is smaller in HDBS condition [0.29–0.79] than in control condition [10–90]. (F) Graphic representation of the projections of minimum (circles) and maximum (squares) concentration on the principal component analysis on PC1 for the six selected animals. The distance from minimum to maximum is bigger in control condition (black) than with HDBS (red). (G) Mean PC1 minimum to maximum distances decreased by HDBS (n = 6), *p < 0.01.

Mentions: To investigate the first parameter, i.e. the effect of HDBS on the concentration range that elicits measurable glomerular responses, for each glomerulus, we fixed the response intensity parameter by normalizing the experimentally obtained odor responses to the maximum response for each condition. We obtained a full response range from 0 to 100% for each condition, which allowed us to assess the effects of HDBS on the concentration range in every condition regardless of its effect on induced response intensity. We fit the normalized responses to sigmoid curves as function of Log odor concentration as previously described in control and HDBS conditions (Fig. 6A). Then, we compared the Log concentrations that elicited 10%, 50% and 90% of the maximum response for each condition (respectively Log EC10, Log EC50 and Log EC90) (Fig. 6B). As expected, HDBS significantly shifted the Log EC10 by 0.93 Log units towards lower concentrations (control Log EC10: −1.53 ± 0.05; HDBS Log EC10: −2.46 ± 0.05, df = 103, t = 16.46, p < 0.001). A smaller shift of the Log EC50 (by 0.5 Log units) was induced by HDBS (control LogEC50: −1.13 ± 0.05; HDBS LogEC50: −1.63 ± 0.04, t = 14.67, df = 103, n = 104, p < 0.001). However, the Log EC90 was not affected by HDBS (control Log EC90: −0.52 ± 0.07; HDBS Log EC90: −0.51 ± 0.07, df = 103, t = 0.14, p = 0.88). By shifting the EC10 towards a lower concentration and keeping the EC90 fixed, HDBS flattens the slope of the linear part of the curve (control: 2.38 ± 0.34, HDB: 1.15 ± 0.11, t = 3.51, df = 103, p < 0.001). Consequently, the concentration range that elicits responses between the lower and higher plateaus of the curve broadens34. These data indicate that HDBS decreases the theoretical odor concentration needed to elicit threshold responses but does not change the concentration that evokes the maximum responses, regardless of their absolute value. To experimentally verify this finding based on theoretical sigmoid fit, we identified a subset of glomeruli that displayed sub-threshold responses at weak odor concentrations under control conditions. We then compared their relative to maximum control ΔF/F at that concentration in control and HDBS conditions. In these glomeruli, HDBS significantly increased responses above threshold (control = 5.2 ± 0.5%, HDBS = 39.7 ± 4.9%, paired t-test, t = 6.83, df = 27, p < 0.001) (Fig. 6C,D). Overall, HDBS broadens the range of concentrations that elicit odor responses by increasing glomerular sensitivity to relatively weak odor input and decreasing glomerular activation threshold.


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

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

Functional implications of HDBS on unitary and population glomerular odor coding.(A) Log concentration–response curves in control and HDBS conditions. Odor responses are normalized to every condition’s maximum response. Log EC10, 50 and 90 are determined by the projection on the x axis of the crossing point of the curves with the blue (y = 0.1) grey (y = 0.5) and the green (y = 0.9) lines respectively. Log EC10 and 50 are shifted to the left by HDBS (red) compared to control (black), while Log EC90 is similar for both conditions. (B) Average Log EC10, 50 and 90 in control and HDBS conditions. HDBS significantly decreases Log EC10 by 0.93 Log unit and Log EC50 by 0.5 Log unit while not affecting EC90. (C) Responses of the dorsal OB (4× magnification) surface to 0.1% methyl valerate in control and HDBS conditions. HDBS increases the odor responses of the glomeruli activated in control condition and induced odor responses in additional glomeruli (dashed circles) that did not respond in the control condition. (D) Average mean response of the glomeruli that showed below threshold relative ΔF/F. HDBS increases the mean ΔF/F of these glomeruli from 5.2 ± 0.5% in control condition to 39.7 ± 4.9% after HDBS. (E) Log concentration–response curves in control and HDBS conditions for the same glomerulus as in A. Odor responses are normalized to control maximum response. Normalized responses to the Log concentrations EC10 and 90 were compared in both control and HDBS conditions, determined by the projection of the y axis of the crossing point of the curves with the lines x = control EC10 and x = control EC90 respectively. The distance between the Log EC10 and Log EC90 responses is smaller in HDBS condition [0.29–0.79] than in control condition [10–90]. (F) Graphic representation of the projections of minimum (circles) and maximum (squares) concentration on the principal component analysis on PC1 for the six selected animals. The distance from minimum to maximum is bigger in control condition (black) than with HDBS (red). (G) Mean PC1 minimum to maximum distances decreased by HDBS (n = 6), *p < 0.01.
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f6: Functional implications of HDBS on unitary and population glomerular odor coding.(A) Log concentration–response curves in control and HDBS conditions. Odor responses are normalized to every condition’s maximum response. Log EC10, 50 and 90 are determined by the projection on the x axis of the crossing point of the curves with the blue (y = 0.1) grey (y = 0.5) and the green (y = 0.9) lines respectively. Log EC10 and 50 are shifted to the left by HDBS (red) compared to control (black), while Log EC90 is similar for both conditions. (B) Average Log EC10, 50 and 90 in control and HDBS conditions. HDBS significantly decreases Log EC10 by 0.93 Log unit and Log EC50 by 0.5 Log unit while not affecting EC90. (C) Responses of the dorsal OB (4× magnification) surface to 0.1% methyl valerate in control and HDBS conditions. HDBS increases the odor responses of the glomeruli activated in control condition and induced odor responses in additional glomeruli (dashed circles) that did not respond in the control condition. (D) Average mean response of the glomeruli that showed below threshold relative ΔF/F. HDBS increases the mean ΔF/F of these glomeruli from 5.2 ± 0.5% in control condition to 39.7 ± 4.9% after HDBS. (E) Log concentration–response curves in control and HDBS conditions for the same glomerulus as in A. Odor responses are normalized to control maximum response. Normalized responses to the Log concentrations EC10 and 90 were compared in both control and HDBS conditions, determined by the projection of the y axis of the crossing point of the curves with the lines x = control EC10 and x = control EC90 respectively. The distance between the Log EC10 and Log EC90 responses is smaller in HDBS condition [0.29–0.79] than in control condition [10–90]. (F) Graphic representation of the projections of minimum (circles) and maximum (squares) concentration on the principal component analysis on PC1 for the six selected animals. The distance from minimum to maximum is bigger in control condition (black) than with HDBS (red). (G) Mean PC1 minimum to maximum distances decreased by HDBS (n = 6), *p < 0.01.
Mentions: To investigate the first parameter, i.e. the effect of HDBS on the concentration range that elicits measurable glomerular responses, for each glomerulus, we fixed the response intensity parameter by normalizing the experimentally obtained odor responses to the maximum response for each condition. We obtained a full response range from 0 to 100% for each condition, which allowed us to assess the effects of HDBS on the concentration range in every condition regardless of its effect on induced response intensity. We fit the normalized responses to sigmoid curves as function of Log odor concentration as previously described in control and HDBS conditions (Fig. 6A). Then, we compared the Log concentrations that elicited 10%, 50% and 90% of the maximum response for each condition (respectively Log EC10, Log EC50 and Log EC90) (Fig. 6B). As expected, HDBS significantly shifted the Log EC10 by 0.93 Log units towards lower concentrations (control Log EC10: −1.53 ± 0.05; HDBS Log EC10: −2.46 ± 0.05, df = 103, t = 16.46, p < 0.001). A smaller shift of the Log EC50 (by 0.5 Log units) was induced by HDBS (control LogEC50: −1.13 ± 0.05; HDBS LogEC50: −1.63 ± 0.04, t = 14.67, df = 103, n = 104, p < 0.001). However, the Log EC90 was not affected by HDBS (control Log EC90: −0.52 ± 0.07; HDBS Log EC90: −0.51 ± 0.07, df = 103, t = 0.14, p = 0.88). By shifting the EC10 towards a lower concentration and keeping the EC90 fixed, HDBS flattens the slope of the linear part of the curve (control: 2.38 ± 0.34, HDB: 1.15 ± 0.11, t = 3.51, df = 103, p < 0.001). Consequently, the concentration range that elicits responses between the lower and higher plateaus of the curve broadens34. These data indicate that HDBS decreases the theoretical odor concentration needed to elicit threshold responses but does not change the concentration that evokes the maximum responses, regardless of their absolute value. To experimentally verify this finding based on theoretical sigmoid fit, we identified a subset of glomeruli that displayed sub-threshold responses at weak odor concentrations under control conditions. We then compared their relative to maximum control ΔF/F at that concentration in control and HDBS conditions. In these glomeruli, HDBS significantly increased responses above threshold (control = 5.2 ± 0.5%, HDBS = 39.7 ± 4.9%, paired t-test, t = 6.83, df = 27, p < 0.001) (Fig. 6C,D). Overall, HDBS broadens the range of concentrations that elicit odor responses by increasing glomerular sensitivity to relatively weak odor input and decreasing glomerular activation threshold.

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