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In the early morning of February 16, 2022, Beijing time, An'an Li's research group from Xuzhou Medical University published a research paper entitled "VIP interneurons regulate olfactory bulb output and contribute to odor detection and discrimination" in the journal Cell Reports, clarifying that VIP interneurons It plays an important role in the regulation of odor representation and olfactory function in the olfactory bulb
.
Associate Professor Wang Dejuan of Xuzhou Medical University, graduate students Wu Jing and Liu Penglai are the co-first authors of the paper, Professor Li An'an is the corresponding author of the paper, and Professor He Miao of Fudan University participated in the research guidance of this project.
Undergraduate students Li Xiaowen and Li Jiaxin made important contributions to this research
.
This study elucidates the basic properties of vasoactive intestinal peptide-expressing (VIP) neurons, a class of interneurons widely distributed in the outer reticular and glomerular layers of the olfactory bulb, and their relationship with olfactory bulb output neurons - Synaptic connections between mitral and tufted cells (M/Ts) and their important role in olfactory-related behaviors
.
Studies have found that activation of VIP neurons can inhibit spontaneous and odor-evoked M/Ts responses, inhibit odor-evoked beta and high gamma responses, and regulate olfactory information representation
.
Patch-clamp experiments found that VIP neurons formed inhibitory synaptic connections with the output neurons of the olfactory bulb by releasing GABA transmitters
.
Inhibition of VIP neurons increases the firing frequency of mitral cells and decreases the ability of mice to detect and discriminate odors (Figure 1)
.
Figure 1.
Schematic diagram of the regulation of VIP neurons on local olfactory neural circuits and olfactory function
.
The olfactory system is an important part of the sensory nervous system, and it is also the earliest sense in animal evolution
.
The sense of smell plays a very important role in both animal survival and human life
.
Olfactory function is closely related to many diseases.
For example, patients with epilepsy sometimes have olfactory hallucinations before seizures; people with a keen sense of smell later have a reduced sense of smell, which may be related to Parkinson's disease or Alzheimer's disease
.
The study of olfactory perception process and olfactory function can not only reveal the operating principle of the olfactory system itself, but also provide important information for the pathogenesis and early diagnosis of some related diseases
.
The olfactory bulb is the first center of olfactory information transmission, and its internal complex neural circuits can extract and integrate olfactory information from olfactory neurons, and perform complex information processing and corresponding coding
.
M/Ts are two types of projection neurons in the olfactory bulb.
Different types of interneurons in the olfactory bulb play an important role in regulating the output of M/Ts.
Among them, there are a large number of VIP interneurons in the outer reticular layer
.
VIP interneurons play an important role in the processing of cortical sensory information, the formation of key circuits during development, and the maintenance of memory during related behaviors, but their roles in the regulation of olfactory bulb neural circuits and the representation of olfactory information have not yet been established.
There are studies
.
The researchers first clarified the distribution and electrophysiological properties of VIP neurons in the olfactory bulb, and proved that VIP neurons are mainly distributed in the outer reticular layer and the globular layer (Fig.
2A); like other outer reticular layer neurons, VIP neurons receive excitatory neural input to mitral cells (Fig.
2BC)
.
Fiber optic calcium recordings revealed that VIP neurons exhibited inhibitory responses to odors (Fig.
2D)
.
Figure 2.
Electrophysiological properties and odor response characteristics of VIP neurons in the olfactory bulb
.
In order to study the role of VIP neurons in the representation of olfactory information, the researchers used a combination of awake head-fixed in-body electrophysiological recording technology and optogenetic technology to study the effect of activated VIP neurons on the M/Ts electrical activity of olfactory bulb output neurons and the local field of the olfactory bulb.
The effect of Local field potential (LFP)
.
The results showed that light-activated VIP neurons inhibited spontaneous M/Ts electrical activity (Fig.
3A); odors could induce excitatory and inhibitory responses in M/Ts, while light-activated VIP neurons inhibited odor-induced excitability and inhibition sexual response (Figure 3B)
.
Electrical activity provides important information for the representation and encoding of olfactory information from the single-cell level, and LFP can reflect the local neural circuits of the olfactory bulb and the processing and integration of information between the olfactory bulb and other brain regions
.
LFP oscillations in the olfactory bulb, especially beta oscillations and high gamma oscillations, exhibit strong and stable responses to odors and play an important role in odor detection
.
Field potential data indicated that activation of VIP neurons inhibited odor-evoked beta and high gamma oscillations
.
These results suggest that VIP neurons play an important role in the representation of olfactory information
.
Figure 3.
Activation of VIP neurons inhibits spontaneous and odor-evoked M/Ts responses
.
The results of in vivo electrophysiological studies suggest that VIP neurons form inhibitory synaptic connections with olfactory bulb output neurons M/Ts
.
In order to verify this experimental conclusion, the researchers further explored the regulation of VIP neurons on the mitral cells of the olfactory bulb by using the isolated patch clamp technique
.
It was found that, unlike the disinhibition of VIP neurons in the cortex, VIP neurons in the olfactory bulb directly inhibit mitral cells by releasing GABA transmitters (Fig.
4)
.
Figure 4.
VIP neurons form inhibitory synaptic connections with mitral cells
.
Since VIP neurons can inhibit the electrical activity of output neurons in the olfactory bulb and affect the representation of olfactory information, do VIP neurons affect olfactory behavior? The researchers used chemical genetic methods to inactivate VIP neurons in the olfactory bulb and examined olfactory-related behaviors at the behavioral level
.
The study found that inactivating VIP neurons reduced olfactory detection and discrimination in mice (Figure 5), but did not affect innate odor preference and aversive behavior
.
Figure 5.
Inactivation of VIP neurons results in reduced odor detection and discrimination in mice
.
In brief, this work elucidates the important role of VIP neurons in the olfactory bulb in regulating olfactory information representation and olfactory function
.
On the one hand, the results of the study will help to understand the regulation and mechanism of the internal neural circuits of the olfactory bulb on the output of the olfactory bulb and the encoding process of olfactory information in the olfactory bulb
.
On the other hand, it can also provide new clues for the function of VIP interneurons in the brain
.
Related paper information: https://doi.
org/10.
1016/j.
celrep.
2022.
110383
.
Associate Professor Wang Dejuan of Xuzhou Medical University, graduate students Wu Jing and Liu Penglai are the co-first authors of the paper, Professor Li An'an is the corresponding author of the paper, and Professor He Miao of Fudan University participated in the research guidance of this project.
Undergraduate students Li Xiaowen and Li Jiaxin made important contributions to this research
.
This study elucidates the basic properties of vasoactive intestinal peptide-expressing (VIP) neurons, a class of interneurons widely distributed in the outer reticular and glomerular layers of the olfactory bulb, and their relationship with olfactory bulb output neurons - Synaptic connections between mitral and tufted cells (M/Ts) and their important role in olfactory-related behaviors
.
Studies have found that activation of VIP neurons can inhibit spontaneous and odor-evoked M/Ts responses, inhibit odor-evoked beta and high gamma responses, and regulate olfactory information representation
.
Patch-clamp experiments found that VIP neurons formed inhibitory synaptic connections with the output neurons of the olfactory bulb by releasing GABA transmitters
.
Inhibition of VIP neurons increases the firing frequency of mitral cells and decreases the ability of mice to detect and discriminate odors (Figure 1)
.
Figure 1.
Schematic diagram of the regulation of VIP neurons on local olfactory neural circuits and olfactory function
.
The olfactory system is an important part of the sensory nervous system, and it is also the earliest sense in animal evolution
.
The sense of smell plays a very important role in both animal survival and human life
.
Olfactory function is closely related to many diseases.
For example, patients with epilepsy sometimes have olfactory hallucinations before seizures; people with a keen sense of smell later have a reduced sense of smell, which may be related to Parkinson's disease or Alzheimer's disease
.
The study of olfactory perception process and olfactory function can not only reveal the operating principle of the olfactory system itself, but also provide important information for the pathogenesis and early diagnosis of some related diseases
.
The olfactory bulb is the first center of olfactory information transmission, and its internal complex neural circuits can extract and integrate olfactory information from olfactory neurons, and perform complex information processing and corresponding coding
.
M/Ts are two types of projection neurons in the olfactory bulb.
Different types of interneurons in the olfactory bulb play an important role in regulating the output of M/Ts.
Among them, there are a large number of VIP interneurons in the outer reticular layer
.
VIP interneurons play an important role in the processing of cortical sensory information, the formation of key circuits during development, and the maintenance of memory during related behaviors, but their roles in the regulation of olfactory bulb neural circuits and the representation of olfactory information have not yet been established.
There are studies
.
The researchers first clarified the distribution and electrophysiological properties of VIP neurons in the olfactory bulb, and proved that VIP neurons are mainly distributed in the outer reticular layer and the globular layer (Fig.
2A); like other outer reticular layer neurons, VIP neurons receive excitatory neural input to mitral cells (Fig.
2BC)
.
Fiber optic calcium recordings revealed that VIP neurons exhibited inhibitory responses to odors (Fig.
2D)
.
Figure 2.
Electrophysiological properties and odor response characteristics of VIP neurons in the olfactory bulb
.
In order to study the role of VIP neurons in the representation of olfactory information, the researchers used a combination of awake head-fixed in-body electrophysiological recording technology and optogenetic technology to study the effect of activated VIP neurons on the M/Ts electrical activity of olfactory bulb output neurons and the local field of the olfactory bulb.
The effect of Local field potential (LFP)
.
The results showed that light-activated VIP neurons inhibited spontaneous M/Ts electrical activity (Fig.
3A); odors could induce excitatory and inhibitory responses in M/Ts, while light-activated VIP neurons inhibited odor-induced excitability and inhibition sexual response (Figure 3B)
.
Electrical activity provides important information for the representation and encoding of olfactory information from the single-cell level, and LFP can reflect the local neural circuits of the olfactory bulb and the processing and integration of information between the olfactory bulb and other brain regions
.
LFP oscillations in the olfactory bulb, especially beta oscillations and high gamma oscillations, exhibit strong and stable responses to odors and play an important role in odor detection
.
Field potential data indicated that activation of VIP neurons inhibited odor-evoked beta and high gamma oscillations
.
These results suggest that VIP neurons play an important role in the representation of olfactory information
.
Figure 3.
Activation of VIP neurons inhibits spontaneous and odor-evoked M/Ts responses
.
The results of in vivo electrophysiological studies suggest that VIP neurons form inhibitory synaptic connections with olfactory bulb output neurons M/Ts
.
In order to verify this experimental conclusion, the researchers further explored the regulation of VIP neurons on the mitral cells of the olfactory bulb by using the isolated patch clamp technique
.
It was found that, unlike the disinhibition of VIP neurons in the cortex, VIP neurons in the olfactory bulb directly inhibit mitral cells by releasing GABA transmitters (Fig.
4)
.
Figure 4.
VIP neurons form inhibitory synaptic connections with mitral cells
.
Since VIP neurons can inhibit the electrical activity of output neurons in the olfactory bulb and affect the representation of olfactory information, do VIP neurons affect olfactory behavior? The researchers used chemical genetic methods to inactivate VIP neurons in the olfactory bulb and examined olfactory-related behaviors at the behavioral level
.
The study found that inactivating VIP neurons reduced olfactory detection and discrimination in mice (Figure 5), but did not affect innate odor preference and aversive behavior
.
Figure 5.
Inactivation of VIP neurons results in reduced odor detection and discrimination in mice
.
In brief, this work elucidates the important role of VIP neurons in the olfactory bulb in regulating olfactory information representation and olfactory function
.
On the one hand, the results of the study will help to understand the regulation and mechanism of the internal neural circuits of the olfactory bulb on the output of the olfactory bulb and the encoding process of olfactory information in the olfactory bulb
.
On the other hand, it can also provide new clues for the function of VIP interneurons in the brain
.
Related paper information: https://doi.
org/10.
1016/j.
celrep.
2022.
110383
