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Editor’s note iNature is China’s largest academic official account.
It is jointly created by the doctoral team of Tsinghua University, Harvard University, Chinese Academy of Sciences and other units.
The iNature Talent Official Account is now launched, focusing on talent recruitment, academic progress, scientific research information, and interested parties.
Long press or scan the QR code below to follow us
.
iNature, as a function of the basal ganglia circuit, is essential for all aspects of life and movement disorders, such as Parkinson's disease (PD)
.
In PD, the gradual denervation of dopamine in the dorsal striatum leads to the inhibition of direct pathways and the promotion of indirect pathways, and leads to the activation of the subthalamic nucleus (STN) and globus pallidus (GPi)
.
In fact, manipulation of STN or GPi through deep brain stimulation (DBS) can correct motor symptoms in PD patients and animal models
.
STN-DBS greatly suppresses resting tremor and reduces dopaminergic drugs, while GPi-DBS is mainly beneficial for movement disorders and gait
.
These observations indicate that in addition to the STN-GPi loop, other loops also play a role in controlling movement
.
On June 9, 2021, Wang Yizheng’s team from the Cognitive and Brain Science Research Center of the Beijing Institute of Basic Medical Sciences published an online publication titled “STN–ANT plasticity is crucial for the motor control in Signal Transduction and Targeted Therapy (IF=13.
49).
Parkinson's disease model" research paper, which shows that the synaptic plasticity of the STN-ANT loop controls the locomotion behavior of PD model rodents
.
The newly discovered and characterized STN-ANT loop specifically transmits motor signals from the basal ganglia (STN) to the cingulate cortex for sensorimotor integration, and the synaptic plasticity in this loop participates in the regulation of motor deficits in the PD model
.
Analyzing the role of the STN-ANT loop will provide new precise targets for neuronal modulation
.
In summary, the results of this study provide synaptic plasticity to regulate movement control at a comprehensive level (circuits, synapses, and molecules)
.
Movement control as a function of the basal ganglia circuit is essential for all aspects of life and movement disorders, such as Parkinson's disease (PD)
.
In PD, the gradual denervation of dopamine in the dorsal striatum leads to the inhibition of direct pathways and the promotion of indirect pathways, and leads to the activation of the subthalamic nucleus (STN) and the internal globus pallidus (GPi).
These two nuclei are The important nuclear basal ganglion ring during exercise
.
In fact, manipulation of STN or GPi through deep brain stimulation (DBS) can correct motor symptoms in PD patients and animal models
.
STN-DBS greatly suppresses resting tremor and reduces dopaminergic drugs, but increases the risk of falls, while GPi-DBS is mainly beneficial for dyskinesia and gait
.
These observations indicate that in addition to the STN-GPi loop, other loops also play a role in controlling movement
.
The researchers initially mapped the STN projection nucleus through a series of virus tracking studies
.
First, the adeno-associated virus (AAV) expressing enhanced yellow fluorescent protein (EYFP) was injected into the unilateral mouse STN
.
In addition to the well-known brain regions that receive STN projections, such as the outer globus pallidus (GPe) and GPi, EYFP-positive fibers are also evident in the anterior thalamic nucleus (ANT)
.
To further examine this previously unidentified STN-ANT circuit, it was found that most EYFP-positive neurons are excitatory
.
In addition, retrograde virus tracking experiments also confirmed the STN-ANT connection
.
Next, test whether the STN-ANT loop is functionally single-synaptic through optogenetics and whole-cell recording
.
Light stimulation of STN projection fibers on ANT slices induces excitatory postsynaptic currents (EPSC) on ANT neurons, with an average latency of 4.
81 ± 0.
34 ms and an amplitude of 50.
27 ± 13.
69 pA
.
Taken together, these results indicate an undiscovered, single-synaptic and excitatory projection from STN to ANT
.
Since the activity of excitatory STN neurons increases in PD, STN-projecting ANT neurons are mainly excitatory.
Does the activity of ipsilateral ANT increase in PD model rodents
?
In this study, 6-OHDA was injected into the unilateral dorsal striatum (mice) or the medial forebrain tract (MFB) (rats) to induce the obviousness of dopamine neurons in the unilateral substantia nigra compact body (SNc).
Lost to establish a rodent model of partial Parkinson's disease
.
In the partial Parkinson's disease model mice, c-fos expression was significantly enhanced in the ipsilateral ANT, but not in the contralateral ANT
.
The firing rate of neurons in the ipsilateral ANT of PD model rats is much higher than that of the neurons in the contralateral ANT
.
In order to study the role of the enhanced neural activity in STN-ANT in the motor control of PD model mice, the study applied a balance beam test and apomorphine (APO)-induced rotation
.
IBO's ANT injury to PD model mice significantly improved exercise performance, while reducing the time to pass through the beam and the number of contralateral rotations
.
Consistently, inhibition of ANT or STN-ANT loops through optogenetics ameliorated motor deficits
.
Next, we studied how the enhanced STN-ANT neural activity can cause chronic movement abnormalities in PD model mice
.
Since ANT neurons receive glutamatergic input from STN and glutamate receptors are important for the establishment and maintenance of synaptic activity, the study initially examined AMPAR and NMDAR (two important glutamate receptors) Activity in ANT and STN-ANT circuits
.
The AMPAR/NMDAR current ratio is greatly increased in both ANT and STN-ANT circuits, indicating that excitatory synaptic transmission is greatly enhanced in the STN-ANT circuit of PD model mice
.
It is well known that the increased expression of AMPARs (GluR1 is the main component) lacking GluR2 on the postsynaptic membrane is essential for long-term synaptic enhancement
.
Previous reports indicate that GluR1 membrane expression is regulated by phosphorylation of its intracellular carboxy-terminal motif
.
Using phosphorylation site-specific antibodies, the study found that GluR1-S845, but not GluR1-S831, was greatly increased in the ipsilateral ANT, while the expression of total AMPAR-GluR1 did not change
.
Application of H-89 (a specific PKA inhibitor) to ipsilateral ANT or ANT slices prevented increased GluR1-S845 phosphorylation
.
In addition, delivery of H-89 to the ipsilateral ANT alleviated motor deficits in 6-OHDA-treated mice and MPTP-treated mice
.
In order to specifically prevent the phosphorylation of GluR1-S845, the study designed TAT-S845, a cell-permeable peptide containing a sequence that spans the phosphorylation site of PKA in GluR1
.
The application of TAT-S845 alleviated the motor deficit of PD model mice
.
In summary, this study shows that the synaptic plasticity of the STN-ANT loop controls the locomotion behavior of PD model rodents
.
The newly discovered and characterized STN-ANT loop specifically transmits motor signals from the basal ganglia (STN) to the cingulate cortex for sensorimotor integration, and the synaptic plasticity in this loop participates in the regulation of motor deficits in the PD model
.
Analyzing the role of the STN-ANT loop will provide new precise targets for neuronal modulation
.
In summary, the results of this study provide synaptic plasticity to regulate movement control at a comprehensive level (circuits, synapses, and molecules)
.
Reference message: https://
It is jointly created by the doctoral team of Tsinghua University, Harvard University, Chinese Academy of Sciences and other units.
The iNature Talent Official Account is now launched, focusing on talent recruitment, academic progress, scientific research information, and interested parties.
Long press or scan the QR code below to follow us
.
iNature, as a function of the basal ganglia circuit, is essential for all aspects of life and movement disorders, such as Parkinson's disease (PD)
.
In PD, the gradual denervation of dopamine in the dorsal striatum leads to the inhibition of direct pathways and the promotion of indirect pathways, and leads to the activation of the subthalamic nucleus (STN) and globus pallidus (GPi)
.
In fact, manipulation of STN or GPi through deep brain stimulation (DBS) can correct motor symptoms in PD patients and animal models
.
STN-DBS greatly suppresses resting tremor and reduces dopaminergic drugs, while GPi-DBS is mainly beneficial for movement disorders and gait
.
These observations indicate that in addition to the STN-GPi loop, other loops also play a role in controlling movement
.
On June 9, 2021, Wang Yizheng’s team from the Cognitive and Brain Science Research Center of the Beijing Institute of Basic Medical Sciences published an online publication titled “STN–ANT plasticity is crucial for the motor control in Signal Transduction and Targeted Therapy (IF=13.
49).
Parkinson's disease model" research paper, which shows that the synaptic plasticity of the STN-ANT loop controls the locomotion behavior of PD model rodents
.
The newly discovered and characterized STN-ANT loop specifically transmits motor signals from the basal ganglia (STN) to the cingulate cortex for sensorimotor integration, and the synaptic plasticity in this loop participates in the regulation of motor deficits in the PD model
.
Analyzing the role of the STN-ANT loop will provide new precise targets for neuronal modulation
.
In summary, the results of this study provide synaptic plasticity to regulate movement control at a comprehensive level (circuits, synapses, and molecules)
.
Movement control as a function of the basal ganglia circuit is essential for all aspects of life and movement disorders, such as Parkinson's disease (PD)
.
In PD, the gradual denervation of dopamine in the dorsal striatum leads to the inhibition of direct pathways and the promotion of indirect pathways, and leads to the activation of the subthalamic nucleus (STN) and the internal globus pallidus (GPi).
These two nuclei are The important nuclear basal ganglion ring during exercise
.
In fact, manipulation of STN or GPi through deep brain stimulation (DBS) can correct motor symptoms in PD patients and animal models
.
STN-DBS greatly suppresses resting tremor and reduces dopaminergic drugs, but increases the risk of falls, while GPi-DBS is mainly beneficial for dyskinesia and gait
.
These observations indicate that in addition to the STN-GPi loop, other loops also play a role in controlling movement
.
The researchers initially mapped the STN projection nucleus through a series of virus tracking studies
.
First, the adeno-associated virus (AAV) expressing enhanced yellow fluorescent protein (EYFP) was injected into the unilateral mouse STN
.
In addition to the well-known brain regions that receive STN projections, such as the outer globus pallidus (GPe) and GPi, EYFP-positive fibers are also evident in the anterior thalamic nucleus (ANT)
.
To further examine this previously unidentified STN-ANT circuit, it was found that most EYFP-positive neurons are excitatory
.
In addition, retrograde virus tracking experiments also confirmed the STN-ANT connection
.
Next, test whether the STN-ANT loop is functionally single-synaptic through optogenetics and whole-cell recording
.
Light stimulation of STN projection fibers on ANT slices induces excitatory postsynaptic currents (EPSC) on ANT neurons, with an average latency of 4.
81 ± 0.
34 ms and an amplitude of 50.
27 ± 13.
69 pA
.
Taken together, these results indicate an undiscovered, single-synaptic and excitatory projection from STN to ANT
.
Since the activity of excitatory STN neurons increases in PD, STN-projecting ANT neurons are mainly excitatory.
Does the activity of ipsilateral ANT increase in PD model rodents
?
In this study, 6-OHDA was injected into the unilateral dorsal striatum (mice) or the medial forebrain tract (MFB) (rats) to induce the obviousness of dopamine neurons in the unilateral substantia nigra compact body (SNc).
Lost to establish a rodent model of partial Parkinson's disease
.
In the partial Parkinson's disease model mice, c-fos expression was significantly enhanced in the ipsilateral ANT, but not in the contralateral ANT
.
The firing rate of neurons in the ipsilateral ANT of PD model rats is much higher than that of the neurons in the contralateral ANT
.
In order to study the role of the enhanced neural activity in STN-ANT in the motor control of PD model mice, the study applied a balance beam test and apomorphine (APO)-induced rotation
.
IBO's ANT injury to PD model mice significantly improved exercise performance, while reducing the time to pass through the beam and the number of contralateral rotations
.
Consistently, inhibition of ANT or STN-ANT loops through optogenetics ameliorated motor deficits
.
Next, we studied how the enhanced STN-ANT neural activity can cause chronic movement abnormalities in PD model mice
.
Since ANT neurons receive glutamatergic input from STN and glutamate receptors are important for the establishment and maintenance of synaptic activity, the study initially examined AMPAR and NMDAR (two important glutamate receptors) Activity in ANT and STN-ANT circuits
.
The AMPAR/NMDAR current ratio is greatly increased in both ANT and STN-ANT circuits, indicating that excitatory synaptic transmission is greatly enhanced in the STN-ANT circuit of PD model mice
.
It is well known that the increased expression of AMPARs (GluR1 is the main component) lacking GluR2 on the postsynaptic membrane is essential for long-term synaptic enhancement
.
Previous reports indicate that GluR1 membrane expression is regulated by phosphorylation of its intracellular carboxy-terminal motif
.
Using phosphorylation site-specific antibodies, the study found that GluR1-S845, but not GluR1-S831, was greatly increased in the ipsilateral ANT, while the expression of total AMPAR-GluR1 did not change
.
Application of H-89 (a specific PKA inhibitor) to ipsilateral ANT or ANT slices prevented increased GluR1-S845 phosphorylation
.
In addition, delivery of H-89 to the ipsilateral ANT alleviated motor deficits in 6-OHDA-treated mice and MPTP-treated mice
.
In order to specifically prevent the phosphorylation of GluR1-S845, the study designed TAT-S845, a cell-permeable peptide containing a sequence that spans the phosphorylation site of PKA in GluR1
.
The application of TAT-S845 alleviated the motor deficit of PD model mice
.
In summary, this study shows that the synaptic plasticity of the STN-ANT loop controls the locomotion behavior of PD model rodents
.
The newly discovered and characterized STN-ANT loop specifically transmits motor signals from the basal ganglia (STN) to the cingulate cortex for sensorimotor integration, and the synaptic plasticity in this loop participates in the regulation of motor deficits in the PD model
.
Analyzing the role of the STN-ANT loop will provide new precise targets for neuronal modulation
.
In summary, the results of this study provide synaptic plasticity to regulate movement control at a comprehensive level (circuits, synapses, and molecules)
.
Reference message: https://
