Global slowing of network oscillations in mouse neocortex by diazepam.
Benzodiazepines have a broad spectrum of clinical applications including sedation, anti-anxiety, and anticonvulsive therapy. At the cellular level, benzodiazepines are allosteric modulators of GABA(A) receptors; they increase the efficacy of inhibition in neuronal networks by prolonging the duration of inhibitory postsynaptic potentials. This mechanism of action predicts that benzodiazepines reduce the frequency of inhibition-driven network oscillations, consistent with observations from human and animal EEG. However, most of existing data are restricted to frequency bands below ∼30 Hz. Recent data suggest that faster cortical network rhythms are critically involved in several behavioral and cognitive tasks. We therefore analyzed diazepam effects on a large range of cortical network oscillations in freely moving mice, including theta (4-12 Hz), gamma (40-100 Hz) and fast gamma (120-160 Hz) oscillations. We also investigated diazepam effects over the coupling between theta phase and the amplitude fast oscillations. We report that diazepam causes a global slowing of oscillatory activity in all frequency domains. Oscillation power was changed differently for each frequency domain, with characteristic differences between active wakefulness, slow-wave sleep and REM sleep. Cross-frequency coupling strength, in contrast, was mostly unaffected by diazepam. Such state- and frequency-dependent actions of benzodiazepines on cortical network oscillations may be relevant for their specific cognitive effects. They also underline the strong interaction between local network oscillations and global brain states.
Institute for Physiology and Pathophysiology, University Heidelberg, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany.
Claudia
C
Scheffzük
Valeriy I
VI
Kukushka
Alexei L
AL
Vyssotski
Andreas
A
Draguhn
Adriano B L
AB
Tort
Jurij
J
Brankačk
D000818:Animals; D003975:Diazepam / Q000494:pharmacology*; D004569:Electroencephalography / Q000187:drug effects* / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019579:Neocortex / Q000187:drug effects* / Q000502:physiology*; D009415:Nerve Net / Q000187:drug effects* / Q000502:physiology*; D013997:Time Factors
D003975:Diazepam