The vulnerability of SNc DA neurones to cell death is not correlated with NMDA current density or receptor subtypes, but could in part be related to inadequate NMDA receptor desensitization. “
“Neurons sum their input

by spatial and temporal integration. Temporally, presynaptic firing rates are converted to dendritic membrane depolarizations by postsynaptic receptors and ion channels. In several regions of the brain, including higher association areas, the majority of firing rates are low. For rates below 20 Hz, the ionotropic receptors α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and N-methyl-d-aspartate (NMDA) receptor will not produce effective temporal summation. We hypothesized that depolarization

mediated by transient receptor potential (TRP) channels activated by metabotropic glutamate receptors would be Pembrolizumab more effective, owing to their slow kinetics. On the basis of voltage-clamp and current-clamp recordings from a rat slice preparation, we constructed a computational model of the TRP channel and its intracellular activation pathway, including the metabotropic glutamate receptor. We show that synaptic input frequencies down to 3–4 Hz and inputs consisting of as few as three to five pulses can be effectively ERK inhibitor in vivo summed. We further show that the time constant of integration increases with increasing stimulation frequency and duration. We suggest that the temporal summation characteristics of TRP channels may be important at distal dendritic arbors, where spatial summation is limited by the number of concurrently active synapses. It may be particularly important in regions characterized by low and irregular rates. “
“Implantation of electrodes in the subthalamic nucleus (STN) for deep brain stimulation is a well-established method to ameliorate motor symptoms in patients suffering from Parkinson’s disease (PD).

This study investigated the pathophysiology of rest and postural tremor in PD. In 14 patients with PD, we recorded intraoperatively local field potentials (LFPs) in the STN (at different recording depths) and electromyographic signals (EMGs) of the contralateral forearm. Using coherence analysis we analysed tremor epochs both at rest and Anacetrapib hold conditions in patients of the akinetic-rigid or of the tremor-dominant PD subtype. Data analysis revealed significant LFP–EMG coherence during periods of rest and postural tremor. However, strong differences between both tremor types were observed: local maxima (cluster) of rest and postural tremor did not match. Additionally, during rest tremor coherence occurred significantly more frequently at single tremor frequency than at double tremor frequency in tremor-dominant as well as in akinetic-rigid patients. In contrast, during postural tremor in patients with akinetic-rigid PD coherence was predominantly at double tremor frequency.