Morphine disrupts long-range synchrony of gamma oscillations in hippocampal slices

Oscillations in neuronal population activity within the gamma frequency band (>25 Hz) have been correlated with cognition: Gamma oscillations could bind together features of a sensory stimulus by generating synchrony between discrete cortical areas [Eckhorn, R., Bauer, R., Jordan, W., Brosch, M., Kruse, W., Munk, M. & Reitboeck, H. J. (1989) Biol. Cybern. 60, 121-130; Singer, W. & Gray, C. M. (1995) Annu. Rev. Neurosci. 18, 555-556]. Herein we demonstrate that morphine and beta-endorphin disrupt this long-range synchrony of gamma oscillations while leaving the synchrony of local oscillations relatively intact. The effect is caused by a decrease in type A gamma-aminobutyric acid receptor-mediated inhibition of both excitatory pyramidal cells and inhibitory interneurons. The effects of morphine on gamma oscillations were blocked by mu-opioid receptor antagonists but not by antagonists of delta or kappa receptors. Morphine also produced burst firing in interneurons, because synaptic excitation from pyramidal cells was no longer balanced by synchronous inhibitory postsynaptic potentials. The loss of synchrony of gamma oscillations induced by morphine may constitute one mechanism involved in producing the cognitive deficits that this drug causes clinically.