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Why dopamine-containing neurons of the brain's substantia nigra pars compacta die in Parkinson's disease has been an enduring mystery. Our studies suggest that the unusual reliance of these neurons on L-type Ca(v)1.3 Ca2+ channels to drive their maintained, rhythmic pacemaking renders them vulnerable to stressors thought to contribute to disease(More)
Dopaminergic neurons of the substantia nigra pars compacta are autonomous pacemakers. This activity is responsible for the sustained release of dopamine necessary for the proper functioning of target structures, such as the striatum. Somatodendritic L-type Ca2+ channels have long been viewed as important, if not necessary, for this activity. The studies(More)
Neurons in the external segment of the globus pallidus (GPe) are autonomous pacemakers that are capable of sustained fast spiking. The cellular and molecular determinants of pacemaking and fast spiking in GPe neurons are not fully understood, but voltage-dependent Na+ channels must play an important role. Electrophysiological studies of these neurons(More)
Principal medium spiny projection neurons (MSNs) of the striatum have long been thought to be homogeneous in their somatodendritic morphology and physiology. Recent work using transgenic mice, in which the two major classes of MSN are labeled, has challenged this assumption. To explore the basis for this difference, D(1) and D(2) receptor-expressing MSNs(More)
The globus pallidus (GP) is a critical component of the basal ganglia circuitry controlling motor behavior. Dysregulation of GP activity has been implicated in a number of psychomotor disorders, including Parkinson's disease (PD), in which a cardinal feature of the pathophysiology is an alteration in the pattern and synchrony of discharge in GP neurons. Yet(More)
Parkinson's disease is a common neurodegenerative disorder characterized by a profound motor disability that is traceable to the emergence of synchronous, rhythmic spiking in neurons of the external segment of the globus pallidus (GPe). The origins of this pathophysiology are poorly defined for the generation of pacemaking. After the induction of a(More)
The striatum is widely viewed as the fulcrum of pathophysiology in Parkinson's disease (PD) and L-DOPA-induced dyskinesia (LID). In these disease states, the balance in activity of striatal direct pathway spiny projection neurons (dSPNs) and indirect pathway spiny projection neurons (iSPNs) is disrupted, leading to aberrant action selection. However, it is(More)
The symptoms of Parkinson's disease (PD) are related to changes in the frequency and pattern of activity in the reciprocally connected GABAergic external globus pallidus (GPe) and glutamatergic subthalamic nucleus (STN). In idiopathic and experimental PD, the GPe and STN exhibit hypoactivity and hyperactivity, respectively, and abnormal synchronous rhythmic(More)
CA1 pyramidal neurons from animals that have acquired a hippocampus-dependent task show a reduced slow postburst afterhyperpolarization (sAHP). To understand the functional significance of this change, we examined and characterized the sAHP activated by different patterns of synaptic stimuli and its impact on postsynaptic signal integration. Whole cell(More)
Parkinson's disease (PD) is a common neurodegenerative disorder of which the core motor symptoms are attributable to the degeneration of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). Recent work has revealed that the engagement of L-type Ca(2+) channels during autonomous pacemaking renders SNc DA neurons susceptible to mitochondrial(More)