Joshua L. Plotkin

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The loss of striatal dopamine (DA) in Parkinson's disease (PD) models triggers a cell-type-specific reduction in the density of dendritic spines in D(2) receptor-expressing striatopallidal medium spiny neurons (D(2) MSNs). How the intrinsic properties of MSN dendrites, where the vast majority of DA receptors are found, contribute to this adaptation is not(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 control of motor behavior in animals and humans requires constant adaptation of neuronal networks to signals of various types and strengths. We found that microRNA-128 (miR-128), which is expressed in adult neurons, regulates motor behavior by modulating neuronal signaling networks and excitability. miR-128 governs motor activity by suppressing the(More)
Striatal spiny neurons (SPNs) associate a diverse array of cortically processed information to regulate action selection. But how this is done by SPNs is poorly understood. A key step in this process is the transition of SPNs from a hyperpolarized 'down state' to a sustained, depolarized 'up state'. These transitions are thought to reflect a sustained(More)
The striatum is thought to play a central role in learning how to choose acts that lead to reward and avoid punishment. Dopamine-dependent modification of striatal synapses in the action selection circuitry has long been thought to be a key step toward this type of learning. The development of new genetic and optical tools has pushed this field forward in(More)
Despite their small number, fast-spiking (FS) GABAergic interneurons play a critical role in controlling striatal output by mediating cortical feed-forward inhibition of striatal medium-sized spiny (MS) projection neurons. We have examined the functional development of FS interneurons and their cortical inputs, and the expression of three of their molecular(More)
Mice carrying bacterial artificial chromosome (BAC) transgenes have become important tools for neuroscientists, providing a powerful means of dissecting complex neural circuits in the brain. Recently, it was reported that one popular line of these mice--mice possessing a BAC transgene with a D(2) dopamine receptor (Drd2) promoter construct coupled to an(More)
A balanced interaction between dopaminergic and cholinergic signaling in the striatum is critical to goal-directed behavior. But how this interaction modulates corticostriatal synaptic plasticity underlying learned actions remains unclear--particularly in direct-pathway spiny projection neurons (dSPNs). Our studies show that in dSPNs, endogenous cholinergic(More)
The induction of corticostriatal long-term depression (LTD) in striatal spiny projection neurons (SPNs) requires coactivation of group I metabotropic glutamate receptors (mGluRs) and L-type Ca(2+) channels. This combination leads to the postsynaptic production of endocannabinoids that act presynaptically to reduce glutamate release. Although the necessity(More)
Dopamine (DA) is a key regulator of action selection and associative learning. The striatum has long been thought to be a major locus of DA action in this process. Although all striatal cell types express G protein-coupled receptors for DA, the effects of DA on principal medium spiny neurons (MSNs) understandably have received the most attention. In the two(More)