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Pentobarbitone modulates calcium transients in axons and synaptic boutons of hippocampal CA1 neurons.

ABSTRACT: Although barbiturates, like other general anaesthetics, depress excitatory synaptic transmission in the central nervous system (CNS), the underlying cellular mechanisms remain unresolved. They may increase the likelihood that an action potential will fail to invade every branch of the axonal arbour, thereby decreasing the synaptic drive to the postsynaptic neurons. Alternatively, they may inhibit calcium entry into the presynaptic terminals, thus reducing transmitter release. To resolve these issues, we have used two-photon microscopy to monitor calcium transients evoked by action potentials in axons, axonal varicosities (synaptic boutons) and fine axon collaterals of hippocampal CA1 neurons. Pentobarbitone (75-300 microM) did not block the invasion of the axonal arbour or the synaptic boutons, but it did reduce the amplitude of the calcium transients recorded from the axons in a concentration-dependent manner. At 150 microM, pentobarbitone reduced the transients to 78+/-4% of the control. Pentobarbitone depressed the calcium transients recorded from the synaptic boutons in a concentration-dependent manner. When 150 microM pentobarbitone was applied, the calcium transients recorded from the boutons were 53+/-3% of the control. This concentration of pentobarbitone also reduced the amplitude and frequency of the spontaneous excitatory postsynaptic potentials to 54+/-4 and 42+/-17% of the control, respectively. The local anaesthetic procaine (500 microM) had no significant effect on action potential invasion of axon collaterals, even though it reduced the action potential amplitude by 25%. This data are consistent with the notion that the pentobarbitone-induced depression of presynaptic calcium transients contributes to its depressant effect on excitatory synaptic transmission in the CNS.

SUBMITTER: Baudoux S

PROVIDER: S-EPMC1574109 | biostudies-other | 2003 Nov

REPOSITORIES: biostudies-other

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Project description:BackgroundHippocampal CA1 pyramidal neurons receive two excitatory glutamatergic synaptic inputs: their most distal dendritic regions in the stratum lacunosum-moleculare (SLM) are innervated by the perforant path (PP), originating from layer III of the entorhinal cortex, while their more proximal regions of the apical dendrites in the stratum radiatum (SR) are innervated by the Schaffer-collaterals (SC), originating from hippocampal CA3 neurons. Endocannabinoids (eCBs) are naturally occurring mediators capable of modulating both GABAergic and glutamatergic synaptic transmission and plasticity via the CB1 receptor. Previous work on eCB modulation of excitatory synapses in the CA1 region largely focuses on the SC pathway. However, little information is available on whether and how eCBs modulate glutamatergic synaptic transmission and plasticity at PP synapses.Methodology/principal findingsBy employing somatic and dendritic patch-clamp recordings, Ca(2+) uncaging, and immunostaining, we demonstrate that there are significant differences in low-frequency stimulation (LFS)- or DHPG-, an agonist of group I metabotropic glutamate receptors (mGluRs), induced long-term depression (LTD) of excitatory synaptic transmission between SC and PP synapses in the same pyramidal neurons. These differences are eliminated by pharmacological inhibition with selective CB1 receptor antagonists or genetic deletion of the CB1 receptor, indicating that these differences likely result from differential modulation via a CB1 receptor-dependent mechanism. We also revealed that depolarization-induced suppression of excitation (DSE), a form of short-term synaptic plasticity, and photolysis of caged Ca(2+)-induced suppression of Excitatory postsynaptic currents (EPSCs) were less at the PP than that at the SC. In addition, application of WIN55212 (WIN) induced a more pronounced inhibition of EPSCs at the SC when compared to that at the PP.Conclusions/significanceOur results suggest that CB1 dependent LTD and DSE are differentially expressed at the PP versus SC synapses in the same neurons, which may have an impact on synaptic scaling, integration and plasticity of hippocampal CA1 pyramidal neurons.

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Pentobarbitone modulates calcium transients in axons and synaptic boutons of hippocampal CA1 neurons.

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