Cell reveals how male nematode mating behavior drives brain activity

Written | Talking and laughing natural behavior is the action and behavior of a person or animal in a natural state based on their own nature, and it is usually closely related to the environment in which the person or animal is located
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Understanding how brain circuits organize natural behavior requires mapping the interaction between animals, the environment, and the nervous system
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Studies have found that when animals are isolated from the natural environment, brain activity will be significantly weakened [1]
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When animals move freely, neural circuit activity becomes more complicated
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When animals engage in different behaviors, the functional correlation between brain regions will change [2]
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Studies on mice have shown that increasing task complexity and sensory richness will gradually relieve the correlation between neurons and brain regions [3]
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Task-dependent functional reorganization of neuronal circuits can also be observed in invertebrates, vertebrates and artificial systems [4]
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So how does a complete natural behavior integrate with brain structure and function? On September 16, 2021, the team of Aravinthan DT Samuel from Harvard University and the team of Vivek Venkatachalam jointly published a research paper entitled Natural sensory context drives diverse brain-wide activity during C.
elegans mating in Cell magazine
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The study recorded the activity of all neurons in the hindbrain area of ​​freely moving male nematodes (C.
elegans) during the complete mating process through whole-brain neuronal imaging, and found that each neuron is functionally unique, but functionally unique The correlation between the neurons is not fixed, and will change with the dynamic interaction between the animal, the nervous system and the environment
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Male nematodes drive mating behavior through dedicated neural circuits on the tail (the back of the brain containing more than 100 sensory neurons, interneurons, and motor neurons) [5]
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The entire mating process is as follows (Figure 1): First, he looks for hermaphrodite by detecting pheromone
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When touching hermaphrodite, the sensory organs of the tail are pressed on her body, and then the vulva is located by scanning
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During the scan, he would often change the direction of movement, make sharp turns around her head or tail, and slow down at the vulva
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After finding the vulva, insert the mating needle to trigger sperm transfer, and finally enter the resting stage [6]
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All behaviors only occur when the freely moving male interacts with the hermaphrodite
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Figure 1.
Schematic diagram of the mating state of nematodes In order to record the activity of the male's entire hindbrain during the mating process, the author used a custom-made rotating disc confocal microscope that can perform multi-color and multi-neuron imaging [7]
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Nematodes expressing nuclear-localized calcium indicator (GCaMP6s) and red fluorescent protein (mNeptune) were selected to perform single-cell resolution imaging at a rate of 10 vol/s (Figure 2)
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Through continuous imaging, the neuron activity during the whole mating process (initial search, contact, scanning, vulva detection, mating and rest) was recorded
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Through data analysis, the author succeeded in extracting a set of continuous behavioral features that occurred simultaneously with the activity of the neural circuit.

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Figure 2.
Microscopically recorded male nematode mating behavior and neuronal activity (GCaMP6s-nuclear localization calcium indicator, mNeptune-red fluorescent protein).
What if the brain activity triggered by behavioral dynamics is the same among individuals? Is it possible to construct a computer model that can predict animal behavior based on the pattern of changes in brain activity
?
In order to confirm this conjecture, the author used sparse linear regression to construct a series of brain-to-behavior models based on the serial activity of 52 neurons recorded in the experiment and a set of continuous behavior characteristics.
, And verified their accuracy, confirming that the behavior of animals can be accurately predicted through the activity patterns of specific neurons
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For example, a model trained with motor neurons can accurately predict speed and tail curvature (features related to motor output); a model trained with sensory neurons can predict behaviors related to male-androgynous interactions (for example, relative sliding speed) Features
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Subsequently, in order to better understand how neurons interact in the course of behavior, the authors calculated the neuron-neuron and neuron-behavior relationships of all pairs of neuron activity and continuous behavior characteristics.
The correlation between neuron-behavior and neuron-behavior found that the correlation between neuron-neuron and neuron-behavior is basically the same between each animal
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Using hierarchical clustering to group neurons with similar activities, the data shows that certain neuron clusters can well reflect recognized behavioral modules, such as searching, scanning, turning, vulva detection, and mating
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Each cluster represents a group of main neurons related to each behavior module, and some neurons are closely related to neurons in multiple clusters, indicating that a single neuron may participate in multiple behavior modules
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Another type of clustering analysis (link clustering, link clustering) is basically consistent with hierarchical clustering, in which a group of neuron clusters is related to excretory hole detection, which is a behavioral module that has not been described in the mating process
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Further analysis found that each neuron in the circuit is unique in function, indicating that most neurons have a unique activity pattern
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Different and partially overlapping neuron combinations not only lead to different behavior patterns; for different behavior patterns, these neurons may show different correlations
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For example, HOA and HOB sensory neurons are thought to have similar contributions to vulva detection and cessation
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The author found that in the process of vulva detection, HOA and HOB are active at the same time; but during the mating process, HOA activity increases while HOB activity decreases, indicating that the correlation of specific behavior modules diversifies the activities within the brain during mating
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In order to compare the functional relevance of different behavior modules, the author divides each data set into four states: search, courtship, mating, and rest after mating
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A separate correlation matrix is ​​calculated for each state of each data set
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The data shows that compared with comparing different states shown by the same animal, comparing the same states shown by different animals, the neuron-neuron correlation and neuron-behavior correlation are more similar, indicating that the correlation between neurons is not fixed.
It depends on the behavioral background
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Finally, the researchers combined functional imaging, behavior analysis, and single neuron manipulation to analyze in detail the neural circuits in different mating behavior modules, and explain the mechanisms that diversify the brain's activity patterns and give each neuron unique functional characteristics
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In general, the study revealed the functional relationship between all neurons at each step of the mating process through whole brain imaging
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When analyzing the whole brain dynamics in the context of the entire natural behavior, almost every neuron shows a unique activity pattern
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Each behavior pattern has a specific and consistent neural circuit
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As the behavior unfolds, the functional correlation between neurons in the brain changes with the dynamic interaction between the animal, the nervous system, and the environment
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Combining functional imaging, behavior analysis, and single neuron manipulation, the authors identified several behavioral-related neural circuits
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This research analyzes how the integration of sensory perception and motor action in the natural environment produces different whole brain dynamics
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The author believes that this study also has certain limitations.
For example, due to technical limitations, the head and tail ganglia of the nematode cannot be imaged and analyzed at the same time
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Original link: https://doi.
org/10.
1016/j.
cell.
2021.
08.
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(2017).
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[2] Markowitz, JE, Gillis, WF, Beron, CC, et al.
(2018).
The striatum organizes 3D behavior via moment-to-moment action selection .
Cell 174, 44–58.
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[3] Pinto, L.
, Rajan, K.
, DePasquale, B.
, et al.
(2019).
Task-dependent changes in the large-scale dynamics and necessity of cortical regions .
Neuron 104, 810–824.
e9.
[4] Briggman, KL, and Kristan, WB, Jr.
(2008).
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[5] Cook , SJ, Jarrell, TA, Brittin, CA, et al.
(2019).
Whole-animal connectomes of both Caenorhabditis elegans sexes.
Nature 571, 63–71.
[6] Jarrell, TA, Wang, Y.
, Bloniarz, AE , et al.
(2012).
The connectome of a decision-making neural network.
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[7] Venkatachalam, V.
, Ji, N.
, Wang, X.
, Clark, C.
, et al.
(2016).
Pan-neuronal Imaging in roaming Caenorhabditis elegans.
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