Inhibitory synaptic transmission from the substantia nigra pars reticulata to the ventral medial thalamus in mice.

The cortico-basal ganglia-thalamic loop circuit is involved in variety of motor, association and limbic functions. The basal ganglia receive neural information from various areas of the cerebral cortex and transfer them back to the frontal and motor cortex via the ventral medial (VM), and the anterior-ventral lateral thalamic complex. The projection from the basal ganglia to the thalamus is GABAergic, and, therefore, the output from the basal ganglia cannot directly evoke excitation in the thalamic nuclei. The mechanism underlying the information transfer via the inhibitory projection remains unclear. To address this issue, we recorded electrophysiological properties of nigro-thalamic synapses from the VM neuron. We developed a nigro-thalamic slice preparation, in which the projection from the substantia nigra pars reticulata (SNr) to VM nucleus is stored, to enable the selective activation of the projection from the SNr. We characterized synaptic properties and membrane properties of the VM neuron, and developed a VM neuron model to simulate the impacts of SNr inputs on VM neuron activity. Neural simulation suggested that the inhibitory projection from SNr can control neural activity in two ways: a disinhibition from the spontaneous nigral inhibition and a ß-band synchronization evoked by combination of excitation and inhibition of SNr activity.

Regulation of ERK1/2 mitogen-activated protein kinase by NMDA-receptor-induced seizure activity in cortical slices.

Extracellular signal-regulated kinase 1/2 (ERK1/2) that belongs to a subfamily of mitogen-activated protein kinases (MAPKs) plays diverse roles in the central nervous system. Activation of ERK1/2 has been observed in various types of neuronal excitation, including seizure activity in vivo and in vitro, as well as in NMDA-receptor (NMDA-R)-dependent long-term potentiation in the hippocampus. On the other hand, recent studies in cultured neurons have shown that NMDA-R stimulation could result in either ERK1/2 activation or non-activation, depending on the pharmacological manipulations. To assess NMDA-R-dependent regulation of ERK1/2 activity in vivo, here we examined the effect of NMDA-R-induced seizure activity on ERK1/2 activation by using rat cortical slice preparations. NMDA-R-dependent seizure activity introduced by Mg2+ -free condition did not cause ERK1/2 activation. On the other hand, when picrotoxin was added to concurrently suppress GABAA-receptor-mediated inhibition, profound ERK1/2 activation occurred, which was accompanied by strong phospho-ERK1/2-staining in the superficial and deep cortical layer neurons. In this case, prolonged membrane depolarization and enhanced burst action potential firings, both of which were much greater than those in Mg2+ -free condition alone, were observed. Differential ERK1/2 activation was supported by the concurrent selective increase in phosphorylation of a substrate protein, phospho-site 4/5 of synapsin I. These results indicate that NMDA-R activation through a release from Mg2+ -blockade, which accompanies enhancement of both excitatory and inhibitory synaptic transmission, was not enough, but concurrent suppression of GABAergic inhibition, which leads to a selective increase in excitatory synaptic transmission, was necessary for robust ERK1/2 activation to occur within the cortical network.