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Network oscillations at γ frequency band (30–80 Hz), generated by the interaction between inhibitory interneurons and excitatory neurons, have been proposed to be associated with higher brain functions such as learning and memory. Dopamine (DA), one of the major CNS transmitters, modulates hippocampal γ oscillations but the intracellular mechanisms involved remain elusive. In this study, we recorded kainate-induced γ oscillations in the CA3 area of rat hippocampal slices, and found that DA strongly enhanced γ power, which was largely blocked by dopamine receptor 1 (DR1) antagonist SCH23390, receptor tyrosine kinase (RTK) inhibitor UNC569 and ERK inhibitor U0126, partially blocked by D2/3R antagonist raclopride, PKA inhibitor H89 and PI3K inhibitor wortmannin, but not affected by AKT inhibitor TCBN or NMDAR antagonist D-AP5. Our results indicate that DA-mediated γ enhancement is involved in the activation of signaling pathway of DR1/2-RTK-ERK. Our data demonstrate a strong, rapid modulation of DA on hippocampal γ oscillations and provide a new insight into cellular mechanisms of DA-mediated γ oscillations.

Hippocampal network oscillations at gamma frequency band (γ-oscillation, 20–80 Hz) are synchronized synaptic activities generated by the interactions between the excitatory and inhibitory interneurons and are associated with higher brain function such as learning and memory. Despite extensive studies about the modulation of intracellular kinases on synaptic transmission and plasticity, little is known about the effects of these kinases on γ-oscillations. In this study, we examined the effects of several critical intracellular kinases such as cyclic AMP-dependent protein kinase (PKA), protein kinase B (PKB)/Akt, protein kinase C (PKC), extracellular-regulated protein kinases (ERK) and AMP-activated protein kinase (AMPK), known to regulate synaptic transmission, on hippocampal γ-oscillations in vitro. We found that AMPK inhibitor but not PKA, PKC, or ERK inhibitor, strongly enhanced the power of γ-oscillation (γ-power) and that Akt inhibitor weakly increased γ-power. Western blot analysis confirmed that AMPK inhibitor reduced the expression of p-AMPK but not total AMPK. By using the slice whole cell voltage-clamp technique, we found that AMPK inhibitor increased the frequency but not amplitude of spontaneous inhibitory postsynaptic currents (sIPSC) and had no effect on either frequency or amplitude of spontaneous excitatory postsynaptic currents (sEPSC). Therefore, AMPK activation negatively modulates hippocampal γ-oscillation via modulation of the inhibitory neurons.

Background Levetiracetam (LEV), an antiepileptic drug, has been recently demonstrated to improve the cognitive function. Hippocampal theta rhythm (4–12 Hz) is associated with a variety of cognitively related behaviors, such as exploration, locomotion and spatial memory in both humans and animal models. We investigated the effects of LEV on the theta rhythm in the rat hippocampal CA3 area. Results We found that LEV increased the power of theta oscillation in a dose-dependent manner. The increase in theta power can be blocked by GABAA receptor or NMDA receptor antagonists but not by AMPA receptor antagonist, indicating the involvement of GABAA receptor and NMDA receptor in the induction of theta activity. Interestingly, LEV enhancement of theta power can be also blocked by taurine, indicating that LEV induction of theta may be related to the indirect boosting of GABA action via reduction of extrasynaptic GABAA receptor activation. Furthermore, the increased theta power can be partially reduced by mACh receptor antagonist atropine but not by nACh receptor antagonists, suggesting that mACh receptor activation provides excitatory input into local network responsible for LEV induction of theta. Conclusions Our study demonstrated that induction of a synchronized network oscillation, a novel role of LEV may especially benefit for the treatment of the neuronal disorders with impaired theta oscillation and cognitive function.

Gamma frequency oscillations (γ, 30–100 Hz) have been suggested to underlie various cognitive and motor functions. The psychotomimetic drug methamphetamine (MA) enhances brain γ oscillations associated with changes in psychomotor state. Little is known about the cellular mechanisms of MA modulation on γ oscillations. We explored the effects of multiple intracellular kinases on MA modulation of γ induced by kainate in area CA3 of rat ventral hippocampal slices. We found that dopamine receptor type 1 and 2 (DR1 and DR2) antagonists, the serine/threonine kinase PKB/Akt inhibitor and N-methyl-D-aspartate receptor (NMDAR) antagonists prevented the enhancing effect of MA on γ oscillations, whereas none of them affected baseline γ strength. Protein kinase A, phosphoinositide 3-kinase and extracellular signal-related kinases inhibitors had no effect on MA. We propose that the DR1/DR2-Akt-NMDAR pathway plays a critical role for the MA enhancement of γ oscillations. Our study provides an new insight into the mechanisms of acute MA on MA-induced psychosis.