The Infona portal uses cookies, i.e. strings of text saved by a browser on the user's device. The portal can access those files and use them to remember the user's data, such as their chosen settings (screen view, interface language, etc.), or their login data. By using the Infona portal the user accepts automatic saving and using this information for portal operation purposes. More information on the subject can be found in the Privacy Policy and Terms of Service. By closing this window the user confirms that they have read the information on cookie usage, and they accept the privacy policy and the way cookies are used by the portal. You can change the cookie settings in your browser.
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 signaling through M4 muscarinic receptors...
The two principal movement-suppressing pathways of the basal ganglia, the so-called hyperdirect and indirect pathways, interact within the subthalamic nucleus (STN). An appropriate level and pattern of hyperdirect pathway cortical excitation and indirect pathway external globus pallidus (GPe) inhibition of the STN are critical for normal movement and are greatly perturbed in Parkinson’s disease. Here...
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder. The debilitating choreic movements that plague HD patients have been attributed to striatal degeneration induced by the loss of cortically supplied brain-derived neurotrophic factor (BDNF). Here, we show that in mouse models of early symptomatic HD, BDNF delivery to the striatum and its activation of tyrosine-related kinase...
In this issue of Neuron, Threlfell et al. (2012) report that synchronous activation of cholinergic interneurons evokes striatal dopamine release by activating presynaptic nicotinic acetylcholine receptors. These findings call for a fundamental reevaluation of the long-standing view that dopamine and acetylcholine “feud” over control of striatal circuitry.
Salient stimuli redirect attention and suppress ongoing motor activity. This attentional shift is thought to rely upon thalamic signals to the striatum to shift cortically driven action selection, but the network mechanisms underlying this interaction are unclear. Using a brain slice preparation that preserved cortico- and thalamostriatal connectivity, it was found that activation of thalamostriatal...
Only doubling or tripling α-synuclein expression significantly increases the risk of developing Parkinson's disease. In this issue of Neuron, Nemani et al. show that this modest overexpression of α-synuclein does not lead to obvious toxicity in the near term, but impairs glutamate and dopamine release, potentially leading to broad network dysfunction and eventual pathology.
The genetic basis of cognition and behavioral adaptation to the environment remains poorly understood. Here we demonstrate that the histone methyltransferase complex GLP/G9a controls cognition and adaptive responses in a region-specific fashion in the adult brain. Using conditional mutagenesis in mice, we show that postnatal, neuron-specific deficiency of GLP/G9a leads to derepression of numerous...
The controversy about whether dopamine contributes to cell loss in Parkinson's disease takes a new turn as Mosharov et al. in this issue of Neuron demonstrate that Ca 2+ influx through L-type channels elevates dopamine synthesis to potentially toxic levels in vulnerable ventral mesencephalon neurons.
Activity-dependent rapid structural and functional modifications of central excitatory synapses contribute to synapse maturation, experience-dependent plasticity, and learning and memory and are associated with neurodevelopmental and psychiatric disorders. However, the signal transduction mechanisms that link glutamate receptor activation to intracellular effectors that accomplish structural and functional...
Long-term depression (LTD) of the synapse formed between cortical pyramidal neurons and striatal medium spiny neurons is central to many theories of motor plasticity and associative learning. The induction of LTD at this synapse is thought to depend upon D 2 dopamine receptors localized in the postsynaptic membrane. If this were true, LTD should be inducible in neurons from only one of the...
Neurotransmitters modulate sodium channel availability through activation of G protein-coupled receptors, cAMP-dependent protein kinase (PKA), and protein kinase C (PKC). Voltage-dependent slow inactivation also controls sodium channel availability, synaptic integration, and neuronal firing. Here we show by analysis of sodium channel mutants that neuromodulation via PKA and PKC enhances intrinsic...
Striatal medium spiny neurons are principal players in the basal ganglia macrocircuits implicated in an astonishing array of psychomotor disorders, including Parkinson's disease, schizophrenia, Huntington's disease, and drug abuse. Using an elegant combination of 2-photon laser scanning microscopy and 2-photon uncaging of glutamate, Carter and Sabatini (this issue of Neuron) provide our first glimpse...
Voltage-gated Na + channels are major targets of G protein-coupled receptor (GPCR)-initiated signaling cascades. These cascades act principally through protein kinase-mediated phosphorylation of the channel α subunit. Phosphorylation reduces Na + channel availability in most instances without producing major alterations of fast channel gating. The nature of this change in availability...
The most effective treatment for late-stage Parkinson's disease is to electrically stimulate the subthalamic nucleus (STN) at high frequencies. Why this strategy works is unclear. The work by Do and Bean shows that the Na channels in STN neurons have distinctive features-like resurgence-that regulate their spiking behavior, providing new insights into the mechanism of DBS.
Set the date range to filter the displayed results. You can set a starting date, ending date or both. You can enter the dates manually or choose them from the calendar.