title: mGluR5 in cortical excitatory neurons exerts both cell-autonomous and -nonautonomous influences on cortical somatosensory circuit formation.
abstract: Glutamatergic neurotransmission plays important roles in sensory map formation. The absence of the group I metabotropic glutamate receptor 5 (mGluR5) leads to abnormal sensory map formation throughout the mouse somatosensory pathway. To examine the role of cortical mGluR5 expression on barrel map formation, we generated cortex-specific mGluR5 knock-out (KO) mice. Eliminating mGluR5 function solely in cortical excitatory neurons affects, not only the whisker-related organization of cortical neurons (barrels), but also the patterning of their presynaptic partners, the thalamocortical axons (TCAs). In contrast, subcortical whisker maps develop normally in cortical-mGluR5 KO mice. In the S1 cortex of cortical-mGluR5 KO, layer IV neurons are homogenously distributed and have no clear relationship to the location of TCA clusters. The altered dendritic morphology of cortical layer IV spiny stellate neurons in cortical-mGluR5 KO mice argues for a cell-autonomous role of mGluR5 in dendritic patterning. Furthermore, morphometric analysis of single TCAs in both cortical- and global-mGluR5 KO mice demonstrated that in these mice, the complexity of axonal arbors is reduced, while the area covered by TCA arbors is enlarged. Using voltage-clamp whole-cell recordings in acute thalamocortical brain slices, we found that KO of mGluR5 from cortical excitatory neurons reduced inhibitory but not excitatory inputs onto layer IV neurons. This suggests that mGluR5 signaling in cortical excitatory neurons nonautonomously modulates the functional development of GABAergic circuits. Together, our data provide strong evidence that mGluR5 signaling in cortical principal neurons exerts both cell-autonomous and -nonautonomous influences to modulate the formation of cortical sensory circuits.
authors.affiliation: The Cain Foundation Laboratories, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Ballester-Rosado
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Albright
authors.forename: Chia-Shan
authors.initials: CS
authors.lastname: Wu
authors.forename: Chun-Chieh
authors.initials: CC
authors.lastname: Liao
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Lee
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Lu
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D003712:Dendrites / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009434:Neural Pathways / Q000033:anatomy & histology / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000502:physiology*; D013003:Somatosensory Cortex / Q000033:anatomy & histology / Q000166:cytology / Q000502:physiology*; D013788:Thalamus / Q000502:physiology; D014738:Vibrissae / Q000502:physiology
chemical_list: C578936:Grm5 protein, mouse; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate