Anxious and nonanxious mice show similar hippocampal sensory evoked oscillations under urethane anesthesia: difference in the effect of buspirone.

Hippocampal oscillations recorded under urethane anesthesia are proposed to be modulated by anxiolytics. All classes of clinically effective anxiolytics were reported to decrease the frequency of urethane theta; however, recent findings raise concerns about the direct correlation of anxiolysis and the frequency of hippocampal theta. Here, we took advantage of our two inbred mouse strains displaying extremes of anxiety (anxious (AX) and nonanxious (nAX)) to compare the properties of hippocampal activity and to test the effect of an anxiolytic drugs. No difference was observed in the peak frequency or in the peak power between AX and nAX strains. Buspirone (Bus) applied in 2.5 mg/kg decreased anxiety of AX but did not have any effect on nAX as was tested by elevated plus maze and open field. Interestingly, Bus treatment increased hippocampal oscillatory frequency in the AX but left it unaltered in nAX mice. Saline injection did not have any effect on the oscillation. Paired-pulse facilitation was enhanced by Bus in the nAX, but not in the AX strain. Collectively, these results do not support the hypothesis that hippocampal activity under urethane may serve as a marker for potential anxiolytic drugs. Moreover, we could not confirm the decrease of frequency after anxiolytic treatment

GluA1 Phosphorylation Alters Evoked Firing Pattern In Vivo

AMPA and NMDA receptors convey fast synaptic transmission in the CNS. Their relative contribution to synaptic output and phosphorylation state regulate synaptic plasticity. The AMPA receptor subunit GluA1 is central in synaptic plasticity. Phosphorylation of GluA1 regulates channel properties and trafficking. The firing rate averaged over several hundred ms is used to monitor cellular input. However, plasticity requires the timing of spiking within a few ms; therefore, it is important to understand how phosphorylation governs these events. Here, we investigate whether the GluA1 phosphorylation (p-GluA1) alters the spiking patterns of CA1 cells in vivo. The antidepressant Tianeptine was used for inducing p-GluA1, which resulted in enhanced AMPA-evoked spiking. By comparing the spiking patterns of AMPA-evoked activity with matched firing rates, we show that the spike-trains after Tianeptine application show characteristic features, distinguishing from spike-trains triggered by strong AMPA stimulation. The interspike-interval distributions are different between the two groups, suggesting that neuronal output may differ when new inputs are activated compared to increasing the gain of previously activated receptors. Furthermore, we also show that NMDA evokes spiking with different patterns to AMPA spike-trains. These results support the role of the modulation of NMDAR/AMPAR ratio and p-GluA1 in plasticity and temporal coding

GluA1 phosphorylation alters evoked firing pattern in vivo.

AMPA and NMDA receptors convey fast synaptic transmission in the CNS. Their relative contribution to synaptic output and phosphorylation state regulate synaptic plasticity. The AMPA receptor subunit GluA1 is central in synaptic plasticity. Phosphorylation of GluA1 regulates channel properties and trafficking. The firing rate averaged over several hundred ms is used to monitor cellular input. However, plasticity requires the timing of spiking within a few ms; therefore, it is important to understand how phosphorylation governs these events. Here, we investigate whether the GluA1 phosphorylation (p-GluA1) alters the spiking patterns of CA1 cells in vivo. The antidepressant Tianeptine was used for inducing p-GluA1, which resulted in enhanced AMPA-evoked spiking. By comparing the spiking patterns of AMPA-evoked activity with matched firing rates, we show that the spike-trains after Tianeptine application show characteristic features, distinguishing from spike-trains triggered by strong AMPA stimulation. The interspike-interval distributions are different between the two groups, suggesting that neuronal output may differ when new inputs are activated compared to increasing the gain of previously activated receptors. Furthermore, we also show that NMDA evokes spiking with different patterns to AMPA spike-trains. These results support the role of the modulation of NMDAR/AMPAR ratio and p-GluA1 in plasticity and temporal coding.Peer Reviewe

Stimulation-related response of a PAN.

<p>The PSTHs in panels A and B show the activity of the neuron in response to stimulation. A: response to center-out optic flow. B: response to center-in optic flow. The response to random dot patterns (A,B), to center-out optic flow (A) but not to center-in (B) and the beginning of the reward phase are readily observable (A,B). The conventions are the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142526#pone.0142526.g003" target="_blank">Fig 3</a>. In order to decide whether the increased activity at the beginning of the reward phase is purely reward-related or related to stimulus offset, the aborted trials (where the cat had broken the fixation during visual stimulation and therefore got no reward) were also analyzed (C). Panel C is aligned to the time of the breaking of the fixation, which corresponded to the offset of the stimulus because the trial was immediately aborted upon fixation breaking. Note the PSTH peak, which indicates responsiveness to the offset of the stimulus. Furthermore, in order to control for the effects of saccadic activity, the correlation between the interspike intervals and the normalized amplitude of the eye movements recorded during the experiment was computed (D). The linear regression analysis clearly shows the lack of connection (ρ²: 0.02, p>0.05). This means the activity is of no saccadic origin.</p

The number of responsive CN neurons by the different phases of the applied paradigm.

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