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

• Published in: Pflügers Archiv Vol. 467; no. 7; pp. 1551 - 1564
• Main Authors: den Boon, Femke S., Werkman, Taco R., Schaafsma-Zhao, Qiluan, Houthuijs, Kas, Vitalis, Tania, Kruse, Chris G., Wadman, Wytse J., Chameau, Pascal
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.07.2015; Springer Nature B.V
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cells, Cultured; Excitatory Postsynaptic Potentials; Human Physiology; Inhibitory Postsynaptic Potentials; Molecular Medicine; Neuroscience; Neurosciences; Prefrontal Cortex - cytology; Prefrontal Cortex - metabolism; Prefrontal Cortex - physiology; Pyramidal Cells - metabolism; Pyramidal Cells - physiology; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1 - agonists; Receptor, Cannabinoid, CB1 - metabolism; Receptors; Cannabinoids; Whole-cell recording; Prefrontal cortex; Pyramidal cells; Evoked postsynaptic current
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s00424-014-1586-z

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 (CB 1 Rs), expressed in many brain areas including the mPFC, can modulate excitatory and inhibitory neurotransmission , we aimed to determine whether CB 1 R activation results in modifications of the E/I balance. We first confirm the presence of functional presynaptic CB 1 Rs 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 CB 1 R 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 CB 1 Rs may thus be fundamental in the regulation of local PL cortical network excitability and could be the mechanism through which excessive CB 1 R activation (cannabis abuse) affects cognitive functions.