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J Neurophysiol 83: 3287-3293, 2000;
0022-3077/00 $5.00
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The Journal of Neurophysiology Vol. 83 No. 6 June 2000, pp. 3287-3293
Copyright ©2000 by the American Physiological Society

Cannabinoids Modulate Synaptic Strength and Plasticity at Glutamatergic Synapses of Rat Prefrontal Cortex Pyramidal Neurons

Nathalie Auclair,1 Satoru Otani,1 Philippe Soubrie,2 and Francis Crepel1

 1Laboratoire de Neurobiologie et Neuropharmacologie du Developpement, Institut des Neurosciences, Centre National de la Recherche Scientifique-Université Paris VI, 75005 Paris; and  2Sanofi Recherche, 34184 Montpellier, France

Auclair, Nathalie, Satoru Otani, Philippe Soubrie, and Francis Crepel. Cannabinoids Modulate Synaptic Strength and Plasticity at Glutamatergic Synapses of Rat Prefrontal Cortex Pyramidal Neurons. J. Neurophysiol. 83: 3287-3293, 2000. Cannabinoids receptors have been reported to modulate synaptic transmission in many structures of the CNS, but yet little is known about their role in the prefrontal cortex where type I cannabinoid receptor (CB-1) are expressed. In this study, we tested first the acute effects of selective agonists and antagonist of CB-1 on glutamatergic excitatory postsynaptic currents (EPSCs) in slices of rat prefrontal cortex (PFC). EPSCs were evoked in patch-clamped layer V pyramidal cells by stimulation of layer V afferents. Monosynaptic EPSCs were strongly depressed by bath application (1 µM) of the cannabinoid receptors agonists WIN55212-2 (-50.4 ± 8.8%) and CP55940 (-42.4 ± 10.9%). The CB-1 antagonist SR141716A reversed these effects. Unexpectedly, SR141716A alone produced a significant increase of glutamatergic synaptic transmission (+46.9 ± 11.2%), which could be partly reversed by WIN55212-2. In the presence of strontium in the bath, the frequency but not the amplitude of asynchronous synaptic events evoked in layer V pyramidal cells by stimulating layer V afferents, was markedly decreased (-54.2 ± 8%), indicating a presynaptic site of action of cannabinoids at these synapses. Tetanic stimulation (100 pulses at 100 Hz, 4 trains) induced in control condition, no changes (n = 7/18), long-term depression (LTD; n = 6/18), or long-term potentiation (LTP; n = 5/18) of monosynaptic EPSCs evoked by stimulation of layer V afferents. When tetanus was applied in the presence of WIN 55,212-2 or SR141716-A (1 µM) in the bath, the proportion of "nonplastic" cells were not significantly changed (n = 7/15 in both cases). For the plastic ones (n = 8 in both cases), WIN 55,212-2 strongly favored LTD (n = 7/8) at the apparent expense of LTP (n = 1/8), whereas the opposite effect was observed with SR141716-A (7/8 LTP; 1/8 LTD). These results demonstrate that cannabinoids influence glutamatergic synaptic transmission and plasticity in the PFC of rodent.




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