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Requirement of cannabinoid CB 1 receptors in cortical pyramidal neurons for appropriate development of corticothalamic and thalamocortical projections
Author(s) -
Wu ChiaShan,
Zhu Jie,
WagerMiller Jim,
Wang Shan,
O’Leary Dennis,
Monory Krisztina,
Lutz Beat,
Mackie Ken,
Lu HuiChen
Publication year - 2010
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2010.07337.x
Subject(s) - neuroscience , thalamus , endocannabinoid system , biology , somatosensory system , parvalbumin , axon guidance , cannabinoid , axon , receptor , biochemistry
A role for endocannabinoid signaling in neuronal morphogenesis as the brain develops has recently been suggested. Here we used the developing somatosensory circuit as a model system to examine the role of endocannabinoid signaling in neural circuit formation. We first show that a deficiency in cannabinoid receptor type 1 (CB 1 R), but not G‐protein‐coupled receptor 55 (GPR55), leads to aberrant fasciculation and pathfinding in both corticothalamic and thalamocortical axons despite normal target recognition. Next, we localized CB 1 R expression to developing corticothalamic projections and found little if any expression in thalamocortical axons, using a newly established reporter mouse expressing GFP in thalamocortical projections. A similar thalamocortical projection phenotype was observed following removal of CB 1 R from cortical principal neurons, clearly demonstrating that CB 1 R in corticothalamic axons was required to instruct their complimentary connections, thalamocortical axons. When reciprocal thalamic and cortical connections meet, CB 1 R‐containing corticothalamic axons are intimately associated with elongating thalamocortical projections containing DGLβ, a 2‐arachidonoyl glycerol (2‐AG) synthesizing enzyme. Thus, 2‐AG produced in thalamocortical axons and acting at CB 1 Rs on corticothalamic axons is likely to modulate axonal patterning. The presence of monoglyceride lipase, a 2‐AG degrading enzyme, in both thalamocortical and corticothalamic tracts probably serves to restrict 2‐AG availability. In summary, our study provides strong evidence that endocannabinoids are a modulator for the proposed ‘handshake’ interactions between corticothalamic and thalamocortical axons, especially for fasciculation. These findings are important in understanding the long‐term consequences of alterations in CB 1 R activity during development, a potential etiology for the mental health disorders linked to prenatal cannabis use.