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The ventral tegmental area (VTA) is the origin of the marginal dopamine system of the midbrain cortex, which can project to the medial prefrontal cortex, nucleus accumbens, amygdala and other brain regions
.
D2 receptors are mainly expressed on the somital, axons and dendritic of DA neurons in the VTA region, regulating anxiety and depressive behavior
.
D1 receptors, on the other hand, are primarily associated with
cognitive function.
On October 4, 2022, researcher Xiao Lei of the Institute of Brain Sciences of Fudan University published an article in the journal Molecular Psychiatry to reveal the circuit mechanism
of D1 receptors in the VTA region to regulate anxiety behavior.
1
D1 receptors regulate anxious behavior in both directions
Unlike the dense distribution of D2 receptors, D1 receptors are sparsely distributed in the VTA region and are expressed on several types of neurons in this region: 48.8% of dopaminergic neurons, 24.
4% of inhibitory neurons and 43.
1% of excitatory neurons express this receptor
.
The researchers found that female and male mouse VTA brain regions injected D1 receptor agonists to promote the mice to stay in the open field experimental center area and increase the time that the mice were open arms, indicating an anxiolytic effect, while the injection of D1 receptor inhibitors in this region caused anxiety-like behavior disorder
after injection of D1 receptor inhibitors or by reducing D1 receptor expression through viruses.
Figure 1: Anxiolytic and anxiolytic effects of D1 receptors
2
Different types of neurons expressing D1 receptors regulate anxiety behavior
in mice.
Further specific reduction of dopaminergic neurons by virus did not affect the residence time of mice in the open field experimental center area, but reduced the time of mice in the open arm, and reduced the residence time of mice in the open experimental center area and open arm after reducing the excitatory neuron D1 receptor, which played a pro-anxiety effect.
After reducing the inhibitory neuronal D1 receptor, the residence time of mice in the open field experimental center area and open arm was increased, which exerted anxiolytic effects
.
Figure 2: Different neuronal types expressing D1 receptors differently regulate anxiety behavior
3
The VTA-nucleus septal loop regulates anxious behavior
.
Virus tracing experiments also found that D1 receptor-positive neurons in the VTA region also project to the above brain regions, and only photoactivation of the axons of LS projected by D1 receptor-positive neurons in the VTA region promoted the stay time of mice in the central region and open arms, exerting anxiolytic effects
.
After photoactivation of D1 receptor neurons in the VTA region, the activity of neurons in the LS region increases, and electrophysiology records the postsynaptic current in the LS region, which can be blocked by the AMPA receptor antagonist, which indicates that the D1 receptor neurons in the VTA region activate LS region neurons
by releasing glutamate.
Retrograde tracing experiments show that neurons in LS region retrograde project to VTA region mainly to form projections with glutamatergic neurons
.
After pharmacologically blocking the activity of AMPA receptor and NMDA receptor in the LS region, activating the D1 receptor neurons in the VTA region did not cause anxiolytic effects, while after blocking the activity of D1 receptors in the LS region, activating the D1 receptor neurons in the VTA region could still exert an anxiolytic effect
.
These results suggest that D1 receptor neurons in the VTA region form glutamatergic projections with LS regions and regulate anxiety-like behavior
.
Figure 3: VTA-LS loop regulates anxiety
summary
In this paper, it was found that dopamine type 1 receptors are functionally expressed in the VTA region, exert anxiolytic effects after activating the receptor, and cause anxiety-like behaviors
after inhibiting the receptor.
【References】
1.
Tong, Q.
, Cui, X.
, Xu, H.
et al.
D1 receptor-expressing neurons in ventral tegmental area alleviate mouse anxiety-like behaviors via glutamatergic projection to lateral septum.
Mol Psychiatry (2022).
https://doi.
org/10.
1038/s41380-022-01809-y
The images in the article are from references
