[Show abstract][Hide abstract] ABSTRACT: Stressful experiences do not only cause peripheral changes in stress hormone levels, but also affect central structures such as the hippocampus, implicated in spatial orientation, stress evaluation, and learning and memory. It has been suggested that formation of memory traces is dependent on hippocampal gamma oscillations observed during alert behaviour and rapid eye movement sleep. Furthermore, during quiescent behaviour, sharp wave-ripple (SW-R) activity emerges. These events provide a temporal window during which reactivation of memory ensembles occur. We hypothesized that stress-responsive modulators, such as corticosterone (CORT), corticotropin-releasing factor (CRF) and the neurosteroid 3α, 21-dihydroxy-5α-pregnan-20-one (THDOC) are able to modulate gamma oscillations and SW-Rs. Using in vitro hippocampal slices, we studied acute and subacute (2 h) impact of these agents on gamma oscillations in area cornu ammonis 3 of the ventral hippocampus induced by acetylcholine (10 μm) combined with physostigmine (2 μm). CORT increased the gamma oscillations in a dose-dependent fashion. This effect was mediated by glucocorticoid receptors. Likewise, CRF augmented gamma oscillations via CRF type 1 receptor. Lastly, THDOC was found to diminish cholinergic gamma oscillations in a dose-dependent manner. Neither CORT, CRF nor THDOC modulated gamma power when pre-applied for 1 h, 2 h before the induction of gamma oscillations. Interestingly, stress-related neuromodulators had rather mild effects on spontaneous SW-R compared with their effects on gamma oscillations. These data suggest that the alteration of hippocampal gamma oscillation strength in vitro by stress-related agents is an acute process, permitting fast adaptation to new attention-requiring situations in vivo.
European Journal of Neuroscience 10/2014; · 3.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose: Adenosine is considered an endogenous anticonvulsant. However, much less is known about the putative effects of its precursor, ATP, on epilepsy. Therefore, we tested whether ATP and its receptors are able to modulate epileptiform activity in the medial entorhinal cortex of the rat. Methods: Recurrent epileptiform discharges (REDs) were induced by elevating extracellular potassium concentration combined with application of bicuculline in brain slices from naive and pilocarpine-treated chronic epileptic rats. Field potentials were recorded from layer V/VI of the medial entorhinal cortex. Key Findings: REDs in slices from naive animals had a higher incidence and a shorter duration than in slices from chronic epileptic animals. Exogenous application of ATP reversibly reduced the incidence of REDs in naive and chronic epileptic slices via activation of adenosine A(1) receptors without discernible P2 receptor effects. This effect was stronger in slices from chronic epileptic rats. In slices from naive rats, the P2X7 receptor antagonist A 740003 slightly but significantly reduced the amplitude of slow field potentials of REDs. In slices from chronic epileptic rats, none of the P2 receptor antagonists affected the parameters of REDs. Significance: Our results suggest that endogenously released ATP differentially modulates REDs by activation of A(1) and P2X7 receptors. Although it has a minor proepileptic effect by direct activation of P2X7 receptors, its metabolite adenosine reduces the epileptiform activity via activation of A(1) receptors. The exact effect of ATP on neural activity depends on the actual activity of ectonucleotidases and the expression level of the purinergic receptors, which both alter during epileptogenesis. In addition, our data suggest that P2X7 receptor antagonists have a minor antiepileptic effect.
[Show abstract][Hide abstract] ABSTRACT: The present study was designed to investigate the role of extracellular ATP and its receptors on neuronal network activity. Gamma oscillations (30-50 Hz) were induced in the CA3 region of acute rat hippocampal slices by either acetylcholine (ACh) or kainic acid (KA). ATP reduced the power of KA-induced gamma oscillations exclusively by activation of adenosine receptors after its degradation to adenosine. In contrast, ATP suppressed ACh-induced oscillations through both adenosine and ATP receptors. Activation of adenosine receptors accounts for about 55%, activation of P2 receptors for ∼45% of suppression. Monitoring the ATP degradation by ATP biosensors revealed that bath-applied ATP reaches ∼300 times lower concentrations within the slice. P2 receptors were also activated by endogenous ATP since inhibition of ATP-hydrolyzing enzymes had an inhibitory effect on ACh-induced gamma oscillations. More specific antagonists revealed that ionotropic P2X2 and/or P2X4 receptors reduced the power of ACh-induced gamma oscillations whereas metabotropic P2Y(1) receptor increased it. Intracellular recordings from CA3 pyramidal cells suggest that adenosine receptors reduce the spiking rate and the synchrony of action potentials during gamma oscillations whereas P2 receptors only modulate the firing rate of the cells. In conclusion, our results suggest that endogenously released ATP differentially modulates the power of ACh- or KA-induced gamma oscillations in the CA3 region of the hippocampus by interacting with P2X, P2Y and adenosine receptors. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.