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How odor meets emotion: olfactory input recruits a cortical brake

Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024-11-02

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Advanced science (Weinheim, Baden-Wurttemberg, Germany) · Research frontiers

How odor meets emotion: olfactory input recruits a cortical brake

In acutely stressed mice, bergamot essential-oil exposure accompanies improved exploration. Olfactory input to ACC recruits local inhibition to reduce excitatory activity.

AI conceptual illustration: a mouse and bergamot-related olfaction

How can an odor change brain activity? A 2024 Advanced Science study connects behavioral effects of bergamot essential oil with a defined neural route. Exposure increases open-space exploration in acutely restrained mice. Excitatory input from the anterior olfactory nucleus (AON) can recruit inhibitory cells in anterior cingulate cortex (ACC), producing a seemingly paradoxical pattern: stronger activity in an olfactory region accompanies reduced activity in some downstream excitatory cells.

KEY FINDING

AON input to ACC and local GABAergic inhibition contribute to reduced anxiety-like behavior after essential-oil exposure; excitatory input can reduce another population’s activity through interneurons.

Contents · 7 sections

Exposed-space exploration increases

After acute restraint, mice spend less time in the open-field center and elevated-plus-maze open arms. Essential-oil-exposed mice spend more time there and enter more often, while total travel distance shows no clear change. The difference concerns where they explore rather than a general increase in movement.

The outcome depends on tested conditions: the lower concentration and an odorless control oil do not produce comparable behavioral improvement. Stressed mice prefer the oil side in real-time place choice, whereas unstressed mice show no clear preference. Odor-related choices depend on the animal’s state.

Original figure 1Exposed-space exploration and odor-side choice
Exposed-space exploration and odor-side choice
Original Figure 1: essential-oil exposure increases exposed-space exploration with similar total distance; stressed mice prefer the oil-associated side.
Source: Zhu MY et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · CC BY
Original figure and English caption ↗

Odor increases AON activity

AON participates in olfactory processing. Essential-oil exposure increases its c-Fos activity markers, predominantly in glutamatergic cells. Calcium recordings also capture a rapid response in a mainly excitatory AON population, unlike saline controls.

The lower concentration also activates AON without clear exploration improvement. Recruiting local activity and producing the full behavioral effect are distinct. Inhibiting this AON population reduces exposed-space exploration after oil exposure, supporting its contribution under the tested stress conditions.

Original figure 2AON odor responses and cellular inhibition
AON odor responses and cellular inhibition
Original Figure 2: oil exposure increases AON activity markers and calcium responses; AON-cell inhibition reduces subsequent exposed-space exploration.
Source: Zhu MY et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · CC BY
Original figure and English caption ↗

One input reaches two cellular populations

Olfactory information reaches the olfactory bulb, then AON and other areas before entering higher-order processing networks. The question is not simply whether odor is detected, but how signals reach stress-related cortex and alter relationships among its local cells.

AON output reaches ACC and several other regions. Focusing on the stress-related ACC, tracing shows AON excitatory cells directly contacting both glutamatergic and GABAergic inhibitory populations.

Excitatory input describes the incoming signal but does not determine the region’s overall outcome. Recruiting local inhibitory cells can reduce another population’s activity. Synaptic recordings next follow this branch to examine transmission.

Original figure 3AON connections to two ACC populations
AON connections to two ACC populations
Original Figure 3: anterograde and retrograde tracing support AON excitatory connections to both excitatory and inhibitory ACC cells.
Source: Zhu MY et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · CC BY
Original figure and English caption ↗

Exciting interneurons reduces downstream activity

In slices, AON-terminal activation evokes excitatory synaptic responses in ACC cells, with excitatory cells also receiving a later inhibitory response. Activating ACC GABAergic cells directly likewise evokes inhibitory currents in local excitatory neurons, supporting a cortical inhibitory relay.

In vivo calcium recordings show a matching population pattern: AON activation increases ACC GABAergic activity and decreases activity in a mainly excitatory population. Olfactory input can thus reduce activity in the measured excitatory ACC population through interneurons.

Original figure 4Synaptic responses and opposing in vivo activity changes
Synaptic responses and opposing in vivo activity changes
Original Figure 4: synaptic responses involving AON input and local ACC GABA cells, plus opposite calcium changes in two ACC populations after AON activation.
Source: Zhu MY et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · CC BY
Original figure and English caption ↗

Two altered populations shift in opposite directions

At the lower tested concentration, ACC c-Fos labeling shows no clear change, further indicating that an upstream AON response need not coincide with a change in downstream regional state.

In stressed mice, ACC excitatory-population calcium activity rises while GABAergic activity declines. Oil exposure decreases the former and increases the latter. Slice firing responses to current input shift correspondingly, linking behavioral improvement with opposing cellular adjustments.

Inhibiting ACC-projecting AON cells weakens these activity changes; inhibiting ACC GABAergic cells also reduces the oil-associated exploration benefit. The study progressively links upstream olfactory responses, local cortical activity and behavioral choice.

Original figure 5State changes in two ACC populations
State changes in two ACC populations
Original Figure 5: ACC calcium activity and excitability under stress and oil exposure, alongside changes after AON projection-cell inhibition.
Source: Zhu MY et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · CC BY
Original figure and English caption ↗

Activating the input also changes exploration

Activating AON terminals in ACC increases stressed-mouse center and open-arm time while total distance remains similar. The intervention reproduces the behavioral direction, supporting the connection’s capacity to regulate exploration after stress.

Conversely, inhibiting these terminals during oil exposure reduces exposed-space exploration. Activation and inhibition test the connection from both directions: it can drive behavioral changes and contributes to the oil-related benefit in this model, within a wider olfactory network containing other AON outputs.

Original figure 6Behavioral effects of AON-terminal activation and inhibition
Behavioral effects of AON-terminal activation and inhibition
Original Figure 6: AON-terminal activation in ACC increases exposed-space exploration after stress, while terminal inhibition reduces the oil-associated benefit.
Source: Zhu MY et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · CC BY
Original figure and English caption ↗

Odor effects depend on the network they enter

These findings come from an acute-stress model in adult male mice and describe how odor-related input and local inhibition contribute to exploration. They connect olfaction with emotion-related cortex through specific cellular relationships and show how excitatory input can produce different activity outcomes through local circuitry.

Publication details

Zhu MY, Dong WY, Guo JR, Huang JY, Cheng PK, Yang Y, Liu A, Yang XL, Zhu X, Zhang Z, Wang Y, Tao W.
A Neural Circuit For Bergamot Essential Oil-Induced Anxiolytic Effects
Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024-11-02
DOI: 10.1002/advs.202406766