title: Activation of type-1 cannabinoid receptor shifts the balance between excitation and inhibition towards excitation in layer II/III pyramidal neurons of the rat prelimbic cortex.
abstract: Activation of the endocannabinoid (eCB) system by exogenous cannabinoids (drug abuse) can alter the physiology of the brain circuits involved in higher-order cognitive functions such as the medial prefrontal cortex (mPFC). A proper balance between excitation and inhibition (E/I balance) is critical for neuronal network oscillations underlying cognitive functions. Since type-1 cannabinoid receptors (CB1Rs), expressed in many brain areas including the mPFC, can modulate excitatory and inhibitory neurotransmission, we aimed to determine whether CB1R activation results in modifications of the E/I balance. We first confirm the presence of functional presynaptic CB1Rs that can modulate both excitatory and inhibitory inputs to layer II/III pyramidal neurons of the prelimbic (PL) area of the mPFC. By decomposing the synaptic response evoked by layer I stimulation into its excitatory and inhibitory components, we show that in vitro CB1R activation with the cannabinoid receptor agonists WIN55,212-2 (WIN) and CP-55940 (CP) modulates the balance between excitation and inhibition (E/I balance) of layer II/III pyramidal neurons. This treatment caused a significant shift of the E/I balance towards excitation, from 18/82 % to 25/75 % (WIN) and from 17/83 to 30/70 % (CP). Finally, when animals were injected with a cannabinoid receptor agonist, we observed a shift of the E/I balance (measured in vitro) towards excitation 1 h after WIN (24/76 %) or after CP injection (30/70 %) when compared to vehicle-injected animals (18/82 %). This modulation of the E/I balance by CB1Rs may thus be fundamental in the regulation of local PL cortical network excitability and could be the mechanism through which excessive CB1R activation (cannabis abuse) affects cognitive functions.
authors: Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, Netherlands.
authors: Femke S
authors: FS
authors: den Boon
authors: Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, Netherlands. T.R.Werkman@uva.nl.
authors: Taco R
authors: TR
authors: Werkman
authors: Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, Netherlands.
authors: Qiluan
authors: Q
authors: Schaafsma-Zhao
authors: Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, Netherlands.
authors: Kas
authors: K
authors: Houthuijs
authors: CNRS-UMR 7637, Brain Plasticity Unit, ESPCI ParisTech, 10 rue Vauquelin, 75005, Paris, France.
authors: Tania
authors: T
authors: Vitalis
authors: Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, Netherlands.
authors: Chris G
authors: CG
authors: Kruse
authors: Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, Netherlands.
authors: Wytse J
authors: WJ
authors: Wadman
authors: Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, Netherlands.
authors: Pascal
authors: P
authors: Chameau
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials; D053444:Inhibitory Postsynaptic Potentials; D017397:Prefrontal Cortex / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D017966:Pyramidal Cells / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000378:metabolism*
chemical_list: D043884:Receptor, Cannabinoid, CB1