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Altering cannabinoid signaling during development disrupts neuronal activity
C. Bernard *,
M. Milh *,
Y. M. Morozov *,,
Y. Ben-Ari *,
T. F. Freund, and
H. Gozlan * ,
*Institut de Neurobiologie de la MéditerranéeInstitut National de la Santé et de la Recherche Médicale U29, 163 Route de Luminy BP13, 13273 Marseille Cédex 09, France; and Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest 8., Szigony u. 43, H-1083, Hungary
Edited by Ricardo Miledi, University of California, Irvine, CA
Accepted for publication April 26, 2005.
Received for publication December 22, 2004.
In adult cortical tissue, recruitment of GABAergic inhibitionprevents the progression of synchronous population dischargesto epileptic activity. However, at early developmental stages,GABA is excitatory and thus unable to fulfill this role. Here,we report that retrograde signaling involving endocannabinoidsis responsible for the homeostatic control of synaptic transmissionand the resulting network patterns in the immature hippocampus.Blockade of cannabinoid type 1 (CB1) receptor led to epilepticdischarges, whereas overactivation of CB1 reduced network activityin vivo. Endocannabinoid signaling thus is able to keep populationdischarge patterns within a narrow physiological time window,balancing between epilepsy on one side and sparse activity onthe other, which may result in impaired developmental plasticity.Disturbing this delicate balance during pregnancy in eitherdirection, e.g., with marijuana as a CB1 agonist or with anantagonist marketed as an antiobesity drug, can have profoundconsequences for brain maturation even in human embryos.