Inhibitory glutamate receptor channels: Characterization and modulation in cultured lobster stomatogastric neurons, or, It's amazing it works at all.

摘要

The spiny lobster stomatogastric ganglion (STG) is a central pattern generator; the intrinsic properties of its 27-32 identified neurons and the inhibitory synapses which connect them into a functional network generate rhythmic bursts of action potentials atop characteristic slow membrane potential oscillations in each participating neuron. As most of the neurons in the STG are motoneurons, innervating striated muscles in the foregut, this rhythmicity is directly linked to behavior. The strength and phasing of bursting in each of these motoneurons depend on the influences of extrinsic chemical modulators on the membrane and synaptic properties of each neuron, and on the recurrent effects of the modulated neurons upon one another.; Inhibitory glutamate receptor channels (IGluRs), which are present throughout the protostome clade and subsume a variety of roles in different species and tissues, mediate the majority of the intraganglionic synapses which underlie rhythmicity and burst phasing within the STG. In order to study IGluR-mediated currents directly, individual STG neurons were extracted and plated into primary culture. Glutamate-gated currents were studied under voltage clamp at the whole-cell level and in excised outside-out membrane patches at the single-channel level. The evoked currents were mediated primarily by chloride, along with a small potassium dependence; their pharmacology fell comfortably within the range of variation of the IGluR receptor family (some of which variation appears to be phylogenetically correlated). The lobster IGluRs were GABA-insensitive; an important concern given known GABA crossactivation of other IGluRs and the presence of GABAergic descending inputs to the STG.; The neuromodulators dopamine and serotonin are each capable of inducing characteristic rhythmicity in the STG and reproducibly altering the strengths of many identified glutamatergic synapses. Of these two, dopamine reliably reduced the IGluR-mediated current in cultured neurons, while serotonin had no effect on any IGluR within the sample tested. These studies and their results join a growing effort to understand systemic regulation at a more reduced level, in which individual effectors and intracellular pathways, and their interrelationships, constitute the fundamental building blocks of pattern generation, or, more generally, of systemic neural control.