Abstract
The metabotropic glutamate receptor subtype 1 (mGluR1) is a major subtype of group I mGluRs, which contributes to the development and plasticity of synapses in the brain. In the sensory thalamus, the thalamocortical neuron receives sensory afferents and massive feedback input from corticothalamic (CT) fibers. Notably, mGluR1 is more concentrated in CT synapses in the sensory thalamus. In the visual thalamus, mGluR1 maintains mature afferent synaptic connectivity. However, it is unknown whether mGluR1 contributes to strengthening of immature synapses or weakening of excess synapses during development and whether mGluR1 at CT synapses heterosynaptically regulates the development or refinement of afferent synapses. Here we investigated the effects of knocking out the gene encoding mGluR1 or pharmacologically blocking cortical activity on the development and maintenance of lemniscal synapses, i.e., the somatosensory afferent synapses, in the ventral posteromedial somatosensory thalamus. mGluR1-knockout (KO) mice exhibited delayed developmental strengthening as well as incomplete elimination and remodeling after maturation of lemniscal synapses. Similar to the phenotypes exhibited by mGluR1-KO mice, pharmacological blockade of somatosensory cortical activity from P12 or P21 for 1 week in wild-type mice perturbed elimination or maintenance of lemniscal synapses, respectively. The same manipulation in mGluR1-KO mice failed to induce additional abnormalities in lemniscal synaptic connectivity. These results suggest that activation of mGluR1, driven by CT input, regulates multiple stages of the development of lemniscal synapses, including strengthening, refinement, and maintenance in the somatosensory thalamus.
Highlights
The development of synaptic connectivity involves initial formation, strengthening, and maintenance of synapses or weakening, pruning, and repression of the formation of excess synapses
Unlike dLGN, in which the expression of mGluR1α significantly increased from P21, the expression in ventral posteromedial nucleus (VPm) was stable among the sampled ages compared with that in VPm at P0
We showed that the activation of metabotropic glutamate receptors (mGluRs) subtype 1 (mGluR1) plays multiple roles in development and maintenance of afferent synapses in the somatosensory thalamus. mGluR1-KO mice exhibit delayed strengthening, incomplete elimination, and failure to maintain lemniscal synapses
Summary
The development of synaptic connectivity involves initial formation, strengthening, and maintenance of synapses or weakening, pruning, and repression of the formation of excess synapses. In the sensory areas of the brain in particular, spontaneous and sensory experiencedependent activities control the development and refinement of precise synaptic connectivity [1,2,3,4,5]. Such mechanisms are defined in the afferent synapses of the sensory thalamus, which are the relay center for sensory information [6,7,8]. CT input activates mGluR1, and this activation may regulate developmental strengthening of synapses and neural connectivity
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