Activation of postsynaptic metabotropic glutamate receptors by trans- ACPD hyperpolarizes neurons of the basolateral amygdala

Abstract

Glutamate has traditionally been regarded as an excitatory neurotransmitter. Synaptic activation of ionotropic glutamate receptors mediates fast EPSPs in the CNS. Moreover, activation of metabotropic glutamate receptors (mGluRs), which are coupled to second messenger effector systems via GTP-binding proteins (G-proteins), results in the expression of slow EPSPs. We have now examined the response of basolateral amygdala (BLA) neurons to activation of postsynaptic mGluRs. In approximately 78% of BLA neurons examined, activation of postsynaptic mGluRs results in membrane hyperpolarization and an associated decrease in membrane input resistance or a hyperpolarization followed by a depolarization associated with an increase in input resistance. The purpose of this study was to address the mechanisms underlying the membrane hyperpolarization. Here, we report that the ACPD-induced hyperpolarization is insensitive to TTX, is dependent on extracellular K+ concentrations, and has a reversal potential (-84 mV) close to that estimated from the Nernst equation for an increase in a K+ conductance. In addition, the ACPD response is resistant to (1) intracellular chloride loading, (2) the GABAB receptor antagonist CGP55845A, (3) the ACh receptor antagonist atropine, and (4) the ionotropic glutamate receptor antagonists CNQX and APV. These data suggest that the hyperpolarization results from a direct activation of postsynaptic mGluRs on neurons of the BLA. Furthermore, we performed studies that suggest that the hyperpolarization is G-protein mediated and results from activation of a TEA-sensitive, calcium-dependent potassium conductance. The sensitivity of this conductance to thapsigargin further suggests that this response requires the release of calcium from intracellular stores. In summary, these data suggest a role for glutamate as an inhibitory transmitter in the BLA during periods of metabotropic glutamate receptor activation. In nuclei such as the BLA that are exquisitely sensitive to seizure induction, an inhibitory response to glutamate may act to delay the onset of epileptogenesis.

Identification of cell-type-specific promoters within the brain using lentiviral vectors

“…11,12,28 A block of tissue containing the hippocampus was then mounted on the chuck of a Leica VTS-1000 vibrating microtome (Leica Microsystems Inc., Bannockburn, IL, USA), and 350 mm coronal slices were cut. Slices were then hemisected and transferred to a holding chamber containing ACSF KA at room temperature and gassed with a 95-5% oxygen/carbon dioxide mixture for 1 h before being placed in oxygenated control ACSF containing (in mM): NaCl (130), KCl (3.5), KH 2 PO 4 (1.1), MgCl 2 (1.3), CaCl 2 (2.5), NaHCO 3 (30) and glucose (10).…”

“…Whole-cell patch clamp recordings were obtained with standard techniques, as described previously. 11,12,28 Briefly, recordings were made with an Axopatch-1D amplifier (Molecular Devices, Sunnyvale, CA, USA) using a Digidata 1320A A-D interface and pClamp 8.2 software (Molecular Devices). In cell-attached mode, patch electrode seal resistance was considered acceptable if it was 41.5 GO.…”

Competition between Calcium-Activated K+Channels Determines Cholinergic Action on Firing Properties of Basolateral Amygdala Projection Neurons

“…It has been proposed that activation of calcium-activated potassium channels may be neuroprotective, delaying the onset of epileptogenesis during periods of enhanced neuronal activity (Rainnie et al, 1994). SK channel activation may also act to uncouple large postsynaptic calcium rises from neuronal output, ensuring that calciumdependent changes necessary for synaptic plasticity are not passed on to downstream targets of BLA projection neurons.…”

Group I mGluRs Evoke K-ATP Current by Intracellular Ca2+Mobilization in Rat Subthalamus Neurons

“…Although this late inhibitory postsynaptic current was dependent upon Ca 21 release from InsP 3 -and ryanodine-sensitive calcium stores, the outward current was mediated by apamin-sensitive Ca 21 -activated K1 channels rather than K-ATP channels (Fiorillo and Williams, 1998). A gKCa-mediated inhibitory postsynaptic current has also been described in basolateral amygdala neurons that is dependent upon a thapsigargin-sensitive release of intracellular Ca 21 by group I mGluR stimulation (Rainnie et al, 1994). Sharifullina et al (2005) reported that DHPG-induced membrane oscillations and burst firing were blocked by a sulfonylurea agent in hypoglossal neurons, but they ascribed the K-ATP current to reduced levels of intracellular ATP.…”