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Written | Edited by Qi | How the undifferentiated cells in the early embryos of Zyme can transform into intricate neuronal networks is still an unsolved mystery.
"The father of modern neuroscience"-Santiago Ramóny Cajal once inferred the principles of axon guidance and neural circuit formation through morphological studies of single neurons.
In the process of searching for answers, he was not limited to a region of the nervous system or a specific model organism.
On the contrary, through extensive investigations, he understood the common characteristics of neuronal development across systems and species, and assembled modern neural circuits.
The understanding of the mechanism lays the foundation.
Each neural circuit is assembled with relatively limited molecules and developmental steps, from the determination of cell fate to the perfection of synapses that depend on activity, thereby helping us perceive and interact with the world.
Although the assembled "toolbox" is shared, how can individual neural circuits obtain their unique properties from it? Recently, the LV Goodric team from Harvard Medical School in the United States published a review titled Making sense of neural development by comparing wiring strategies for seeing and hearing in Science.
In this article, the author chose two significant The phylogeny of different tissue models, namely the visual and auditory systems of vertebrates, presents the subtleties of neurodevelopment and emphasizes the flexibility and complexity of the mechanisms used to construct a functional nervous system.
The similarities and differences in the construction of visual and auditory circuits are in the visual system.
The dynamic three-dimensional scene is captured by the photoreceptors in the retina and transmitted to the brain through the afferent nerves of the retinal ganglion cell (RGC).The local microcircuits in the vertebrate retina perform parallel calculations to analyze changes in contrast, color, movement and direction, and intensity, and the output of these calculations is completed by various RGCs subtypes.
Many RGC axons pass through the optic chiasm and project to different targets, including the dorsolateral geniculate nucleus of the thalamus, the superior colliculus, and many accessory nuclei and non-imaging retinal receptor nuclei.
Retinotopy is the main organizing principle that runs through this approach, followed by binocularity and RGC subtype recognition.
In the auditory system, auditory stimuli are detected by hair cells, which are arranged in frequency, that is, spiraling from the high frequency at the bottom of the cochlea to the low frequency at the top of the cochlea.
The frequency and intensity of the stimulation are encoded by the activity of spiral ganglion neurons (SGNs), which are arranged in parallel with the hair cells.
SGNs directly receive input from hair cells and transmit the central axon from the cochlea to the brain stem through the auditory nerve.
After entering the brainstem, the axons bifurcate and dominate the ventral and dorsal branches of the cochlear nucleus complex, which is the only cochlear receptor target.
In the auditory brainstem nucleus, multiple calculations are performed in parallel to locate sounds in space, coordinate binaural processing, and distinguish between prominent sounds and background noise.
It should be noted that many visual calculations are locally initiated in the retina, while similar auditory calculations mainly occur in the brainstem.
Therefore, the load of afferent neurons in the two systems is different, and this difference may be reflected in the degree of heterogeneity of sensory organs.
In the mouse retina, there are more than 40 RGC subtypes that receive and transmit highly resolved sensory information.
In contrast, in the cochlea, only 4 SGN subtypes can quickly transmit sensory information from hair cells directly to the brain stem.
. In addition, the central projections of afferent nerves are also significantly different.
RGC axons innervate nearly 50 central nuclei in rodents, and project to the same side or the opposite side of the midline to produce binocular vision, while mammalian SGN axons only Projection to the cochlear nucleus complex is completely ipsilateral.
In summary, the auditory and visual systems are in terms of the number and role of afferent neuron subtypes, the balance between peripheral and central calculations in the circuit, and wiring patterns (such as where the information from both sides of the head is integrated).
All are different.
Both the retina and the cochlea contain two different types of sensory receptor cells: the rods and cone photoreceptors on the outside of the retina detect weak and bright light, respectively, and the cones provide additional information about color; while in the cochlea, there are two types The hair cells are present in the auditory sensory epithelium, and one row of inner hair cells is separated from the three rows of outer hair cells (see Figure 1 below).
However, only the inner hair cells can directly capture sound information, while the outer hair cells amplify the signal.
The fate of these basic sensory receptor cells is determined by the transcription level of the early action.
For example, Otx2 and Prdm1 drive the development of retinal precursor cells toward the photoreceptor.
The fate of the photoreceptor is further subdivided by the master regulator NRL, which is inhibiting vision.
The fate of cones simultaneously coordinates the rod gene regulatory network.
Similarly, Atoh1 and Gfi1 induced the fate of cochlear progenitor cells to differentiate into hair cells, while Insm1 and Helios promoted the fate of differentiation into outer hair cells.
Therefore, although different transcription factors are involved, the general principle is the same, that is, to define the fate of a sensory receptor, and then perform additional fate decisions to gradually limit cell characteristics.
Figure 1.
Schematic diagram of the local circuit of the cochlea.
By comparing how neurons find their synaptic partners in the retina and cochlea, we can deepen our understanding of neurodevelopment.
In the rodent retina, there are 15 bipolar cell subtypes, 63 amacrine cell subtypes, and 45 RGC subtypes.
Through "first projecting dendrites to a specific layer, and then interacting with specific postsynaptic cells in the layer) The strategy of "partner pairing" realizes the specific connection of many neuronal subtypes with multiple synaptic partners (see Figure 2 below). Similarly, although there are fewer neuronal subtypes in the cochlea, synaptic pairing also has its rules to follow, that is, restricting type I SGN to project to one row of inner hair cells, while type II SGN to project beyond the inner hair cells to three rows of outer hair cells .
Combining examples of visual and auditory systems, linking many mechanisms found in the entire nervous system to establish synaptic specificity, and together emphasizes the study of how the interaction between fate determination, activity, and synapse formation produces circuits with different structures value.
Figure 2.
Schematic diagram of the local circuit of the retina.
Normally, the "birthday" of a neuron roughly corresponds to its position in the sensory organs, and this distribution is maintained during development.
Research evidence from the visual system supports the hypothesis that the order of neuron production affects the molecular and cellular mechanisms of axon guidance and target domination.
However, when establishing a central connection, RGCs and SGNs axons face different local guidance decisions.
The information about the characteristics of visual stimuli transmitted by RGCs has been partially processed by microcircuit calculations.
Their axons traverse a long distance and dominate multiple central targets through highly organized midline intersections and abundant branches.
The SGNs in the auditory system directly connect sensory receptor cells with central central target cells.
Most of the stimulus processing occurs in the auditory brainstem.
Their axons extend a relatively short distance and reach the only cochlear receiving target only on the same side.
The zone is the cochlear nucleus, and it branches there to dominate the three sub-zones.
So far, we know very little about the mechanism of the key differences in central axon navigation between SGN and RGC.
As with other characteristics of development, the simple presence or absence of a molecule can have profound effects.
The stereotyped bifurcation of SGN axons in the cochlear nucleus complex depends on Npr2, while RGC axons may require a wider range of molecular types and regulatory mechanisms.
With limited cues available for brain wiring, it is not surprising that many molecules are shared in the developing sensory system.
The study of how the same molecule functions in different environments highlights the importance of molecular diversity in creating circuit specialization, such as the receptor tyrosine kinase Ephs and its ligand ephrin.
The Eph/ephrin gradient guides retinal axons to the appropriate area, while the role of Ephs and ephrins in the auditory system is more local than that in the visual system.
The Eph/ephrin signal restricts the axons to the appropriate area of the auditory brainstem.
In the target area, separate the ipsilateral and contralateral input to the targeted neuron, which can cause the SGN peripheral protrusions in the cochlea to be bundled into bundles.
The similarity of the functions of Ephs and ephrins in the auditory and visual systems seems to be more obvious in the separation of midline axons.
For example, EphB1 and ephrin-B2 mediate the divergence of ipsilateral RGC axons in radial glial cells of the optic chiasm of mammals.
Although the auditory projection from the cochlea lacks an optic chiasm-like structure, the Eph signal still guides the development of contralateral projections in the auditory brainstem.
When Ephs or ephrins are disturbed, the contralateral projection axons from neurons in the ventral nucleus of the cochlea will Form an abnormal ipsilateral branch.
Therefore, the formation of circuits in the visual and auditory systems seems to rely on overlapping but different mechanisms.
Summary and Prospects In the past 100 years, developmental neurobiologists have successfully defined the basic principles of neural circuit construction, from cell fate determination to axon guidance and neural network drawing, usually by modeling systems and circuits Look for commonalities in.
The next challenge is how to coordinate these individual events to create a circuit with special functions.
The enlightenment from Ramóny cajal is that if we look for significant differences across systems, we may be able to better describe the flexibility and dynamic range of developmental processes, and it will also help us understand how molecular networks coordinate circuit assembly, not just It is only the content obtained from the study of discrete events on a gene-by-gene basis.
For example, the analysis of the entire nervous system of Caenorhabditis elegans inspired a new idea that circuits can be defined by shared transcription factor motifs.
Similarly, studying the generation of heterogeneity in SGN and RGC may provide clues as to whether cell populations with greater subtype diversity are essentially different from the strategies used by populations with relatively less subtype diversity, which is important for our understanding of cells.
The plasticity of characteristics is of great significance, both in the developing brain and in the mature brain.
By studying multiple types of circuits with different patterns, we can begin to understand the various strategies used to connect to the nervous system and reveal the rules governing how and when a particular strategy is used.
In addition, if we want to try to understand the neural basis of individual differences in humans, we must learn how the subtleties in the circuit structure are generated.
Of course, with the advent of advanced visualization and manipulation of developing circuits, we can now Higher resolution and depth to characterize the development of neural circuits, thereby expanding our knowledge of the construction of diverse circuits required for complex behavior.
Original link: https://doi.
org/10.
1126/science.
aaz6317 Platemaker: Instructions for reprinting on the 11th [Original article] BioArt original article, personal reposting and sharing are welcome, reprinting is prohibited without permission, the copyright of all published works is Owned by BioArt.
BioArt reserves all statutory rights and offenders must be investigated.
"The father of modern neuroscience"-Santiago Ramóny Cajal once inferred the principles of axon guidance and neural circuit formation through morphological studies of single neurons.
In the process of searching for answers, he was not limited to a region of the nervous system or a specific model organism.
On the contrary, through extensive investigations, he understood the common characteristics of neuronal development across systems and species, and assembled modern neural circuits.
The understanding of the mechanism lays the foundation.
Each neural circuit is assembled with relatively limited molecules and developmental steps, from the determination of cell fate to the perfection of synapses that depend on activity, thereby helping us perceive and interact with the world.
Although the assembled "toolbox" is shared, how can individual neural circuits obtain their unique properties from it? Recently, the LV Goodric team from Harvard Medical School in the United States published a review titled Making sense of neural development by comparing wiring strategies for seeing and hearing in Science.
In this article, the author chose two significant The phylogeny of different tissue models, namely the visual and auditory systems of vertebrates, presents the subtleties of neurodevelopment and emphasizes the flexibility and complexity of the mechanisms used to construct a functional nervous system.
The similarities and differences in the construction of visual and auditory circuits are in the visual system.
The dynamic three-dimensional scene is captured by the photoreceptors in the retina and transmitted to the brain through the afferent nerves of the retinal ganglion cell (RGC).The local microcircuits in the vertebrate retina perform parallel calculations to analyze changes in contrast, color, movement and direction, and intensity, and the output of these calculations is completed by various RGCs subtypes.
Many RGC axons pass through the optic chiasm and project to different targets, including the dorsolateral geniculate nucleus of the thalamus, the superior colliculus, and many accessory nuclei and non-imaging retinal receptor nuclei.
Retinotopy is the main organizing principle that runs through this approach, followed by binocularity and RGC subtype recognition.
In the auditory system, auditory stimuli are detected by hair cells, which are arranged in frequency, that is, spiraling from the high frequency at the bottom of the cochlea to the low frequency at the top of the cochlea.
The frequency and intensity of the stimulation are encoded by the activity of spiral ganglion neurons (SGNs), which are arranged in parallel with the hair cells.
SGNs directly receive input from hair cells and transmit the central axon from the cochlea to the brain stem through the auditory nerve.
After entering the brainstem, the axons bifurcate and dominate the ventral and dorsal branches of the cochlear nucleus complex, which is the only cochlear receptor target.
In the auditory brainstem nucleus, multiple calculations are performed in parallel to locate sounds in space, coordinate binaural processing, and distinguish between prominent sounds and background noise.
It should be noted that many visual calculations are locally initiated in the retina, while similar auditory calculations mainly occur in the brainstem.
Therefore, the load of afferent neurons in the two systems is different, and this difference may be reflected in the degree of heterogeneity of sensory organs.
In the mouse retina, there are more than 40 RGC subtypes that receive and transmit highly resolved sensory information.
In contrast, in the cochlea, only 4 SGN subtypes can quickly transmit sensory information from hair cells directly to the brain stem.
. In addition, the central projections of afferent nerves are also significantly different.
RGC axons innervate nearly 50 central nuclei in rodents, and project to the same side or the opposite side of the midline to produce binocular vision, while mammalian SGN axons only Projection to the cochlear nucleus complex is completely ipsilateral.
In summary, the auditory and visual systems are in terms of the number and role of afferent neuron subtypes, the balance between peripheral and central calculations in the circuit, and wiring patterns (such as where the information from both sides of the head is integrated).
All are different.
Both the retina and the cochlea contain two different types of sensory receptor cells: the rods and cone photoreceptors on the outside of the retina detect weak and bright light, respectively, and the cones provide additional information about color; while in the cochlea, there are two types The hair cells are present in the auditory sensory epithelium, and one row of inner hair cells is separated from the three rows of outer hair cells (see Figure 1 below).
However, only the inner hair cells can directly capture sound information, while the outer hair cells amplify the signal.
The fate of these basic sensory receptor cells is determined by the transcription level of the early action.
For example, Otx2 and Prdm1 drive the development of retinal precursor cells toward the photoreceptor.
The fate of the photoreceptor is further subdivided by the master regulator NRL, which is inhibiting vision.
The fate of cones simultaneously coordinates the rod gene regulatory network.
Similarly, Atoh1 and Gfi1 induced the fate of cochlear progenitor cells to differentiate into hair cells, while Insm1 and Helios promoted the fate of differentiation into outer hair cells.
Therefore, although different transcription factors are involved, the general principle is the same, that is, to define the fate of a sensory receptor, and then perform additional fate decisions to gradually limit cell characteristics.
Figure 1.
Schematic diagram of the local circuit of the cochlea.
By comparing how neurons find their synaptic partners in the retina and cochlea, we can deepen our understanding of neurodevelopment.
In the rodent retina, there are 15 bipolar cell subtypes, 63 amacrine cell subtypes, and 45 RGC subtypes.
Through "first projecting dendrites to a specific layer, and then interacting with specific postsynaptic cells in the layer) The strategy of "partner pairing" realizes the specific connection of many neuronal subtypes with multiple synaptic partners (see Figure 2 below). Similarly, although there are fewer neuronal subtypes in the cochlea, synaptic pairing also has its rules to follow, that is, restricting type I SGN to project to one row of inner hair cells, while type II SGN to project beyond the inner hair cells to three rows of outer hair cells .
Combining examples of visual and auditory systems, linking many mechanisms found in the entire nervous system to establish synaptic specificity, and together emphasizes the study of how the interaction between fate determination, activity, and synapse formation produces circuits with different structures value.
Figure 2.
Schematic diagram of the local circuit of the retina.
Normally, the "birthday" of a neuron roughly corresponds to its position in the sensory organs, and this distribution is maintained during development.
Research evidence from the visual system supports the hypothesis that the order of neuron production affects the molecular and cellular mechanisms of axon guidance and target domination.
However, when establishing a central connection, RGCs and SGNs axons face different local guidance decisions.
The information about the characteristics of visual stimuli transmitted by RGCs has been partially processed by microcircuit calculations.
Their axons traverse a long distance and dominate multiple central targets through highly organized midline intersections and abundant branches.
The SGNs in the auditory system directly connect sensory receptor cells with central central target cells.
Most of the stimulus processing occurs in the auditory brainstem.
Their axons extend a relatively short distance and reach the only cochlear receiving target only on the same side.
The zone is the cochlear nucleus, and it branches there to dominate the three sub-zones.
So far, we know very little about the mechanism of the key differences in central axon navigation between SGN and RGC.
As with other characteristics of development, the simple presence or absence of a molecule can have profound effects.
The stereotyped bifurcation of SGN axons in the cochlear nucleus complex depends on Npr2, while RGC axons may require a wider range of molecular types and regulatory mechanisms.
With limited cues available for brain wiring, it is not surprising that many molecules are shared in the developing sensory system.
The study of how the same molecule functions in different environments highlights the importance of molecular diversity in creating circuit specialization, such as the receptor tyrosine kinase Ephs and its ligand ephrin.
The Eph/ephrin gradient guides retinal axons to the appropriate area, while the role of Ephs and ephrins in the auditory system is more local than that in the visual system.
The Eph/ephrin signal restricts the axons to the appropriate area of the auditory brainstem.
In the target area, separate the ipsilateral and contralateral input to the targeted neuron, which can cause the SGN peripheral protrusions in the cochlea to be bundled into bundles.
The similarity of the functions of Ephs and ephrins in the auditory and visual systems seems to be more obvious in the separation of midline axons.
For example, EphB1 and ephrin-B2 mediate the divergence of ipsilateral RGC axons in radial glial cells of the optic chiasm of mammals.
Although the auditory projection from the cochlea lacks an optic chiasm-like structure, the Eph signal still guides the development of contralateral projections in the auditory brainstem.
When Ephs or ephrins are disturbed, the contralateral projection axons from neurons in the ventral nucleus of the cochlea will Form an abnormal ipsilateral branch.
Therefore, the formation of circuits in the visual and auditory systems seems to rely on overlapping but different mechanisms.
Summary and Prospects In the past 100 years, developmental neurobiologists have successfully defined the basic principles of neural circuit construction, from cell fate determination to axon guidance and neural network drawing, usually by modeling systems and circuits Look for commonalities in.
The next challenge is how to coordinate these individual events to create a circuit with special functions.
The enlightenment from Ramóny cajal is that if we look for significant differences across systems, we may be able to better describe the flexibility and dynamic range of developmental processes, and it will also help us understand how molecular networks coordinate circuit assembly, not just It is only the content obtained from the study of discrete events on a gene-by-gene basis.
For example, the analysis of the entire nervous system of Caenorhabditis elegans inspired a new idea that circuits can be defined by shared transcription factor motifs.
Similarly, studying the generation of heterogeneity in SGN and RGC may provide clues as to whether cell populations with greater subtype diversity are essentially different from the strategies used by populations with relatively less subtype diversity, which is important for our understanding of cells.
The plasticity of characteristics is of great significance, both in the developing brain and in the mature brain.
By studying multiple types of circuits with different patterns, we can begin to understand the various strategies used to connect to the nervous system and reveal the rules governing how and when a particular strategy is used.
In addition, if we want to try to understand the neural basis of individual differences in humans, we must learn how the subtleties in the circuit structure are generated.
Of course, with the advent of advanced visualization and manipulation of developing circuits, we can now Higher resolution and depth to characterize the development of neural circuits, thereby expanding our knowledge of the construction of diverse circuits required for complex behavior.
Original link: https://doi.
org/10.
1126/science.
aaz6317 Platemaker: Instructions for reprinting on the 11th [Original article] BioArt original article, personal reposting and sharing are welcome, reprinting is prohibited without permission, the copyright of all published works is Owned by BioArt.
BioArt reserves all statutory rights and offenders must be investigated.
