Activation of adrenoreceptors modulates synaptic transmission in the basolateral amygdala. Here, we investigated the effects of alpha2-adrenoreceptor activation on long-term depression and long-term potentiation in an in vitro slice preparation of the mouse basolateral amygdala. Field potentials and excitatory postsynaptic currents were evoked in the basolateral amygdala by stimulating the lateral amygdala. Norepinephrine (20 micro m) reduced synaptic transmission and completely blocked the induction of long-term potentiation and long-term depression. The alpha2-adrenoreceptor antagonist yohimbine (2 micro m) reversed this effect. The alpha2-adrenoreceptor agonist clonidine (10 micro m) mimicked the effects of norepinephrine. The Gi/o-protein inhibitor pertussis toxin (5 micro g/mL) reversed the effect of clonidine. Long-term depression was blocked in the presence of omega-conotoxin GVIA, but not omega-agatoxin IVA. Clonidine inhibited voltage-activated Ca2+ currents mediated via N- or P/Q-type Ca2+-channels. The inhibitory action of clonidine on long-term depression was reversed when inwardly rectifying K+-channels were blocked by Ba2+ (300 micro m). The present data suggest that alpha2-adrenoreceptor activation impairs the induction of long-term depression in the basolateral amygdala by a Gi/o-protein-mediated inhibition of presynaptic N-type Ca2+-channels and activation of inwardly-rectifying K+-channels.

This study clearly demonstrates that TXA enhances neuronal excitation by antagonizing inhibitory GABAergic neurotransmission. The results provide evidence that this effect is mediated via postsynaptic mechanisms. Because GABAA receptor antagonists are known to promote epileptiform activity, this effect might explain the proconvulsant action of TXA.

Previously, we found that in the lateral amygdala (LA) of the mouse, WIN55,212-2 decreases both glutamatergic and GABAergic synaptic transmission via activation of the cannabinoid receptor type 1 (CB1), yet produces an overall reduction of neuronal excitability. This suggests that the effects on excitatory transmission override those on inhibitory transmission. Here we show that CB1 activation by WIN55,212-2 and ⌬ 9-THC inhibits long-term depression (LTD) of basal synaptic transmission in the LA, induced by low-frequency stimulation (LFS; 900 pulses/1 Hz). The CB1 agonist WIN55,212-2 blocked LTD via G i/o proteins, activation of inwardly rectifying K + channels (K ir s), inhibition of the adenylate cyclase-protein kinase A (PKA) pathway, and PKA-dependent inhibition of voltage-gated N-type Ca 2+ channels (N-type VGCCs). Interestingly, WIN55,212-2 effects on LTD were abolished in CB1 knock-out mice (CB1-KO), and in conditional mutants lacking CB1 expression only in GABAergic interneurons, but were still present in mutants lacking CB1 in principal forebrain neurons. LTD induction per se was unaffected by the CB1 antagonist SR141716A and was normally expressed in CB1-KO as well as in both conditional CB1 mutants. Our data demonstrate that activation of CB1 specifically located on GABAergic interneurons inhibits LTD in the LA. These findings suggest that CB1 expressed on either glutamatergic or GABAergic neurons play a differential role in the control of synaptic transmission and plasticity.The amygdala integrates inputs from various brain regions such as the hippocampus, the prefrontal cortex, and the thalamus, providing a common output and playing an important role in fear memory, triggered reminders of past aversive experiences, and also pain processing (Le Doux 2000;Davis and Whalen 2001;Neugebauer et al. 2004). We previously showed that endocannabinoids released in the amygdala are important for the extinction of aversive memory (Marsicano et al. 2002). Most behavioral effects of exogenously applied cannabinoids (Manning et al. 2001;Pertwee 2001) . In the amygdala, electrophysiological findings also speak in favor of both glutamatergic and GABAergic localization of CB1 receptors. In the lateral amygdala (LA), the agonist WIN55,212-2 reduced isolated glutamatergic and GABAergic currents ) via activation of CB1 receptors. Although it may be assumed that these effects may compensate each other, the application of WIN55,212-2 induced an overall decrease of basal synaptic transmission. This indicates that in the LA, cannabinoid-induced modulation of neuronal activity is mainly determined by CB1 receptors located on excitatory pyramidal neurons.Earlier studies showed that CB1 receptor activation also modulates synaptic plasticity, since cannabinoids influence long-term potentiation and long-term depression (LTD) of synaptic transmission in different brain regions (Misner and Sullivan 1999;Auclair et al. 2000). However, little is known about the mechanisms and the neuronal sites where these CB1-mediated effects are e...

Attempts have been made to attribute the particular features of general anaesthesia such as hypnosis, analgesia, amnesia and autonomic stability to certain brain regions. In the present study, we examined the effects of the commonplace volatile anaesthetic isoflurane on synaptic transmission in an in vitro slice preparation of the murine amygdala. Despite the established role of this limbic structure in the formation of aversive memories, conditioned fear and anxiety, as well as pain processing and regulation of sympathetic tone, the influence of volatile anaesthetics on synaptic signalling has not yet been investigated in this region of the brain. Evoked postsynaptic currents were monitored from principal neurons in the basolateral nucleus of the amygdala by means of patch-clamp recording. The mixed postsynaptic currents were mediated by non-NMDA, NMDA, GABA A and GABA B receptors. Isoflurane added to the perfusion medium reduced the strength of synaptic signalling following the activation of non-NMDA, NMDA, and GABA B receptors, whereas the GABA A receptor-mediated responses were enhanced. The overall reduction of neuronal excitability was also reflected in a reduction of field potential amplitudes. Isoflurane neither changed the membrane resting potential nor the input resistance of principal neurons in the amygdala. The present results may contribute to the understanding of how stress reactions and long-lasting neuroplastic processes are suppressed under general anaesthesia.

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Patients with acute respiratory distress syndrome and acute kidney injury (AKI) treated by kidney replacement therapy may also require treatment with extracorporeal carbon dioxide removal (ECCO2R) devices to permit protective or ultraprotective mechanical ventilation. We developed a mathematical model of acid‐base balance during extracorporeal therapy using ECCO2R and continuous venovenous hemofiltration (CVVH) devices applied in series for the treatment of mechanically ventilated AKI patients. Published data from clinical studies of mechanically ventilated AKI patients treated by CVVH at known infusion rates of substitution fluid without ECCO2R were used to adjust the model parameters to fit plasma levels of arterial partial pressure of carbon dioxide (PaCO2), arterial plasma bicarbonate concentration ([HCO3]), and plasma pH (as well as certain other unmeasured physiological variables). The effects of applying ECCO2R at an unchanged and a reduced tidal volume on PaCO2, [HCO3] and plasma pH were then simulated assuming carbon dioxide removal rates from the ECCO2R device measured in the clinical studies. Agreement of such model predictions with clinical data was good whether the ECCO2R device was positioned proximal or distal to the CVVH device in the extracorporeal circuit. Although carbon dioxide removal rates from the ECCO2R device measured in one previous clinical study were higher when it was placed proximal to the CVVH device, suggesting that such in‐series positioning was optimal, the current mathematical model demonstrates that proximal positioning of the ECCO2R device also results in lower bicarbonate (and, therefore, total carbon dioxide) removal from the distal CVVH device. Thus, the removal of total carbon dioxide by such extracorporeal circuits is relatively independent of the position of the in‐series devices. It is concluded that the described mathematical model has quantitative accuracy; these results suggest that the overall acid‐base balance when using ECCO2R and CVVH devices in a single extracorporeal circuit will be similar, independent of their in‐series position.

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