Integrating Neurotransmission in Striatal Medium Spiny Neurons
The striatum is a major entry structure of the basal ganglia. Its role in information processing in close interaction with the cerebral cortex and thalamus has various behavioral consequences depending on the regions concerned, including control of body m
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Integrating Neurotransmission in Striatal Medium Spiny Neurons Jean-Antoine Girault
Abstract The striatum is a major entry structure of the basal ganglia. Its role in information processing in close interaction with the cerebral cortex and thalamus has various behavioral consequences depending on the regions concerned, including control of body movements and motivation. A general feature of striatal information processing is the control by reward-related dopamine signals of glutamatergic striatal inputs and of their plasticity. This relies on specific sets of receptors and signaling proteins in medium-sized spiny neurons which belong to two groups, striatonigral and striatopallidal neurons. Some signaling pathways are activated only by dopamine or glutamate, but many provide multiple levels of interactions. For example, the cAMP pathway is mostly regulated by dopamine D1 receptors in striatonigral neurons, whereas the ERK pathway detects a combination of glutamate and dopamine signals and is essential for long-lasting modifications. These adaptations require changes in gene expression, and the signaling pathways linking synaptic activity to nuclear function and epigenetic changes are beginning to be deciphered. Their alteration underlies many aspects of striatal dysfunction in pathological conditions which include a decrease or an increase in dopamine transmission, as encountered in Parkinson’s disease or exposure to addictive drugs, respectively. Keywords Cytonuclear signaling • DARPP-32 • Epigenetics • Extracellular signal-regulated kinase • Striatal medium sized spiny neurons
J.-A. Girault (*) Institut du Fer a` Moulin, UMR-S 839, Inserm and Universite´ Pierre et Marie Curie (UPMC), 17 rue du Fer a` Moulin, 75005 Paris, France e-mail: [email protected] M.R. Kreutz and C.Sala (eds.), Synaptic Plasticity, Advances in Experimental Medicine and Biology 970, DOI 10.1007/978-3-7091-0932-8_18, # Springer-Verlag/Wien 2012
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Introduction: An Overview of Striatal Functions and Dysfunctions
The striatum is the largest component of the basal ganglia, a set of interconnected gray matter nuclei located deep in the forebrain, to which it provides a major site of entry. Its name comes from the striate aspect provided by radial crossing of white matter bundles. Although the whole striatum has some common principles of anatomical organization, it is in reality a heterogeneous structure with several types of divisions. A first major division corresponds to its dorsal and ventral parts. In many mammalian species, including carnivores and primates, the dorsal striatum is further separated by the internal capsule into two components, the putamen and the caudate nucleus. In mice or rats, this separation does not exist, and the dorsal striatum is often referred to as the caudate-putamen (CP). The ventral part of the striatum is known as the nucleus accumbens septi (the “nucleus of the septum which is lying down,” although it is not directly connected to the septum) or nucleus accumbens (NA
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