The authors' approach to implantation of DBS leads into the STN was associated with consistent lead placement in the dorsolateral STN, a low rate of morbidity, efficient use of operating room time, and robust improvement in motor function. The mean coordinates of the middle of the electrode array, measured on postoperative MR images, were 11.6 mm lateral, 2.9 mm posterior, and 4.7 mm inferior to the midcommissural point, and 6.5 mm lateral and 3.5 mm anterior to the center of the red nucleus. Voltage thresholds for several types of stimulation-induced adverse effects were predictive of lead location. Technical nuances of the surgery are described in detail.

Background:In Parkinson disease (PD), the benefit of levodopa therapy becomes less marked over

Distinct subtypes of glutamate receptors often are colocalized at individual excitatory synapses in the mammalian brain yet appear to subserve distinct functions. To address whether neuronal activity may differentially regulate the surface expression at synapses of two specific subtypes of ionotropic glutamate receptors we epitope-tagged an AMPA (␣-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor subunit (GluR1) and an NMDA (N-methyl-Daspartate) receptor subunit (NR1) on their extracellular termini and expressed these proteins in cultured hippocampal neurons using recombinant adenoviruses. Both receptor subtypes were appropriately targeted to the synaptic plasma membrane as defined by colocalization with the synaptic vesicle protein synaptophysin. Increasing activity in the network of cultured cells by prolonged blockade of inhibitory synapses with the ␥-aminobutyric acid type A receptor antagonist picrotoxin caused an activity-dependent and NMDA receptor-dependent decrease in surface expression of GluR1, but not NR1, at synapses. Consistent with this observation identical treatment of noninfected cultures decreased the contribution of endogenous AMPA receptors to synaptic currents relative to endogenous NMDA receptors. These results indicate that neuronal activity can differentially regulate the surface expression of AMPA and NMDA receptors at individual synapses.Information about the mechanisms of synaptic transmission and synaptic plasticity in the mammalian brain derives primarily from electrophysiological studies of excitatory synapses in the hippocampus. These synapses use the neurotransmitter glutamate, which can act on distinct subtypes of ionotropic and metabotropic receptors that frequently colocalize at individual synapses but appear to subserve distinct functions (1-3). Two major subtypes of ionotropic receptors, AMPA (␣-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) and NMDA (Nmethyl-D-aspartate) receptors, have been found at virtually all excitatory synaptic connections in the mammalian brain. AMPA receptors (AMPARs) are heteromers of the homologous subunits GluR1-4 and mediate the bulk of synaptic transmission during basal neural activity (1-3). NMDA receptors (NMDARs) also exist as heteromers formed from the NR1 subunit and one or more NR2A-D subunits (1-3). Because of their voltage dependence and high calcium permeability, NMDARs are particularly important for triggering several different forms of synaptic plasticity, including longterm potentiation and long-term depression. When inappropriately activated during a variety of pathological conditions, NMDARs also contribute to neuronal injury and death.It has commonly been assumed that AMPARs and NMDARs are colocalized at individual synapses (1-4), although it is now clear that these receptor subtypes interact with different proteins at the synapse (5). The distinct molecular interactions and functions of these receptor subtypes raise the possibility that their surface expression at synapses may be independently regulated....

Thus far, this gene therapy approach has been well tolerated and shows PET evidence of sustained gene expression. These initial findings demonstrate the safety of the therapy; higher doses of adeno-associated viral vector containing the human aromatic l-amino acid decarboxylase gene in the next cohort of patients may further increase dopamine production in the putamen and provide more profound clinical benefit.

This study provides Class I evidence that paroxetine and venlafaxine XR are effective in treating depression in patients with PD.