Modeling shifts in the rate and pattern of subthalamopallidal network activity during deep brain stimulation.

Deep brain stimulation (DBS) of the subthlamic nucleus (STN) represents an effective treatment for medically refractory Parkinson's disease; however, understanding of its effects on basal ganglia network activity remains limited. We constructed a computational model of the subthalamopallidal network, trained it to fit in vivo recordings from parkinsonian monkeys, and evaluated its response to STN DBS. The network model was created with synaptically connected single compartment biophysical models of STN and pallidal neurons, and stochastically defined inputs driven by cortical beta rhythms.

Network perspectives on the mechanisms of deep brain stimulation.

Deep brain stimulation (DBS) is an established medical therapy for the treatment of movement disorders and shows great promise for several other neurological disorders. However, after decades of clinical utility the underlying therapeutic mechanisms remain undefined. Early attempts to explain the mechanisms of DBS focused on hypotheses that mimicked an ablative lesion to the stimulated brain region.

Pallidal burst activity during therapeutic deep brain stimulation.

Theoretical and experimental analyses of deep brain stimulation (DBS) in the subthalamic nucleus (STN) show both excitatory and inhibitory effects on the neural elements surrounding the electrode. Given these observations, the mechanism underlying the therapeutic effect of STN DBS on parkinsonian motor signs remains under debate. One hypothesis suggests that abnormal levels of bursting activity in the pallidum play a key role in the development of parkinsonian motor signs and that STN DBS may exert its beneficial effect by modifying this type of activity.

Computational analysis of subthalamic nucleus and lenticular fasciculus activation during therapeutic deep brain stimulation.

The subthalamic nucleus (STN) is the most common target for the treatment of Parkinson's disease (PD) with deep brain stimulation (DBS). DBS of the globus pallidus internus (GPi) is also effective in the treatment of PD. The output fibers of the GPi that form the lenticular fasciculus pass in close proximity to STN DBS electrodes.

Depolarization block of neurons during maintenance of electrographic seizures.

Epileptic seizures are associated with neuronal hyperactivity. Here, however, we investigated whether continuous neuronal firing is necessary to maintain electrographic seizures. We studied a class of "low-Ca2+" ictal epileptiform bursts, induced in rat hippocampal slices, that are characterized by prolonged (2-15 s) interruptions in population spike generation.

Ionic mechanisms underlying spontaneous CA1 neuronal firing in Ca2+-free solution.

Hippocampal CA1 neurons exposed to zero-[Ca(2+)] solutions can generate periodic spontaneous synchronized activity in the absence of synaptic function. Experiments using hippocampal slices showed that, after exposure to zero-[Ca(2+)](0) solution, CA1 pyramidal cells depolarized 5-10 mV and started firing spontaneous action potentials. Spontaneous single neuron activity appeared in singlets or was grouped into bursts of two or three action potentials.