Effects of excitatory amino acids and their antagonists on membrane and action potentials of cat caudate neurones.

Abstract

SUMMARY1. The electrical activity of caudate neurones was recorded with intracellular electrodes in halothane anaesthetized cats. Agonists and antagonists of excitatory amino acid receptors were applied by micro-ionophoresis and their effects on membrane-and action potentials and on cortically evoked synaptic potentials evaluated.2. The agonists, L-aspartate (asp), L-glutamate (glu), N-methyl-DL-aspartate (NMA), quinolinate and quisqualate all depolarized the membrane, caused repetitive firing, reduced the apparent amplitude of the cortically evoked excitatory postsynaptic potentials (e.p.s.p.s) and increased the amplitude of the associated inhibitory post-synaptic potential. Two of the agonists, NMA and quinolinate, additionally caused the appearance of up to 500 ms long depolarizations (plateaus) on the falling phase of action potentials. These plateaus were seen in about two-thirds of the cells in this sample while in the other third the excitatory effects of NMA and quinolinate were indistinguishable from those of glu and quisqualate.3. The N-methyl-D-aspartate (NMDA) receptor antagonist D-a-aminoadipate (DAA) reversibly inhibited the effects of NMA and quinolinate but only on those cells where these two agents evoked action potential plateaus while on the same cells the effects of asp, glu and quisqualate were either only weakly antagonized or not affected. On cells not displaying plateaus to NMA or quinolinate none of the effects of the agonists could be antagonized by DAA. DAA applications that completely antagonized the effects of NMA never reduced the amplitudes of cortically evoked e.p.s.p.s.4. Cis-2,3-piperidine dicarboxylate also blocked the effects of NMA and asp at low application currents while at higher currents it enhanced the effects of glu or asp although still retaining its NMA antagonistic activity.5. High-frequency stimulation of the cortico-caudate pathway resulted in longlasting depolarizations and repetitive firing, but plateaus of the type caused by NMA or quinolinate were not seen.

Encoding Network States by Striatal Cell Assemblies

“…Furthermore, application of NMDA to neostriatal circuits in vitro (Vergara et al 2003) and in vivo (Herrling et al 1983) induces bursting activity and generates turning behavior in freely moving animals (Ossowska and Wolfarth 1995), suggesting a general mechanism preserved in a broad range of ages. Structured network dynamics with the same characteristics have been shown in the cortex of young mice in vitro (PD13-22) and adult cats in vivo, demonstrating that network activity, intrinsic to specific nuclei, is preserved in slices (Ikegaya et al 2004).…”

“…Striatal circuits process corticothalamic inputs to produce specific outputs consisting of bursts of action potentials during the execution of motor tasks, probably following voltage transitions to depolarized "up-states" (Hikosaka et al 2000;Kasanetz et al 2006;Mahon et al 2006;Romo et al 1992;Schultz et al 1993;Wilson 1993). As in other isolated nervous tissue preparations known to contain CPGs (e.g., Guertin and Hounsgaard 1998), addition of NMDA to neostriatal circuits in vitro (Vergara et al 2003) and in vivo (Herrling et al 1983) induces recurrent bursting and pattern generation in single neurons. Moreover, intrastriatal application of NMDA in vivo generates turning behavior when administered unilaterally in freely moving animals (Ossowska and Wolfarth 1995); demonstrating that motor behaviors arise from the striatal processing of enhanced excitatory drives.…”

A Ca2+Threshold for Induction of Spike-Timing-Dependent Depression in the Mouse Striatum

“…These synapses are glutamatergic and produce EPSPs mediated by activation of AMPA and NMDA receptors (Herrling et al, 1983;Calabresi et al, 1996;Kita, 1996). Because the striatum is involved in certain types of learning (Packard and Knowlton, 2002;Yin and Knowlton, 2006), activity-dependent plasticity in the corticostriatal synapses has been extensively studied (Calabresi et al, 2007;Surmeier et al, 2007;Wickens, 2009).…”

Comparison of Normal and Parkinsonian Microcircuit Dynamics in the Rodent Striatum

“…In the case of fictive locomotion and swimming, a physiological excitatory drive can be generated pharmacologically: by the addition of micromolar NMDA into the bath saline, a maneuver that induces conditional bistability, plateau potentials and recurrent regular bursting (Grillner et al, 1981;Guertin and Hounsgaard, 1998). In the striatal microcircuit robust recurrent bursting is induced by the same pharmacological manipulation in vivo (Herrling et al, 1983) and in vitro (Vergara et al, 2003) obtaining an electrophysiological patterned output from spiny neurons; similar to that previously recorded in both CPGs or suspected CAs. Furthermore, unilateral NMDA administration induces contralateral turning behavior directly relating recurrent burst firing in medium www.intechopen.com spiny neurons with a rhythmic and regular motor behavior (Ossowska, 1995).…”