Postsynaptic integration of glutamatergic and dopaminergic signals in the striatum. 1994

R Kötter
Department of Anatomy and Structural Biology, University of Otago, Medical School, Dunedin, New Zealand.

The aim of this study was to achieve a better understanding of the integration in striatal medium-sized spiny neurons (MSNs) of converging signals from glutamatergic and dopaminergic afferents. The review of the literature in the first section shows that these two types of afferents not only contact the same striatal cell type, but that individual MSNs receive both a corticostriatal and a dopaminergic terminal. The most common sites of convergence are dendritic shafts and spines of MSNs with a distance between the terminals of less than 1-2 microns. The second section focuses on synaptic transmission and second messenger activation. Glutamate, the candidate transmitter of corticostriatal terminals, via different types of glutamate receptors can evoke an increase in intracellular free calcium concentrations. The net effect of dopamine in the striatum is a stimulation of adenylate cyclase activity leading to an increase in cAMP. The subsequent sections present information on calcium- and cAMP-sensitive biochemical pathways and review the regional and subcellular distribution of the components in the striatum. The specific biochemical reaction steps were formalized as simplified equilibrium equations. Parameter values of the model were chosen from published experimental data. Major results of this analysis are: at intracellular free calcium concentrations below 1 microM the stimulation of adenylate cyclase by calcium and dopamine is at least additive in the steady state. Free calcium concentrations exceeding 1 microM inhibit adenylate cyclase, which is not overcome by dopaminergic stimulation. The kinases and phosphatases studied can be divided in those that are almost exclusively calcium-sensitive (PP2B and CaMPK), and others that are modulated by both calcium and dopamine (PKA and PP1). Maximal threonine-phosphorylation of the phosphoprotein DARPP requires optimal concentrations of calcium (about 0.3 microM) and dopamine (above 5 microM). It seems favourable if the glutamate signal precedes phasic dopamine release by approximately 100 msec. The phosphorylation of MAP2 is under essentially calcium-dependent control of at least five kinases and phosphatases, which differentially affect its heterogeneous phosphorylation sites. Therefore, MAP2 could respond specifically to the spatio-temporal characteristics of different intracellular calcium fluxes. The quantitative description of the calcium- and dopamine-dependent regulation of DARPP and MAP2 provides insights into the crosstalk between glutamatergic and dopaminergic signals in striatal MSNs. Such insights constitute an important step towards a better understanding of the links between biochemical pathways, physiological processes, and behavioural consequences connected with striatal function. The relevance to long-term potentiation, reinforcement learning, and Parkinson's disease is discussed.

UI MeSH Term Description Entries
D008959 Models, Neurological Theoretical representations that simulate the behavior or activity of the neurological system, processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment. Neurologic Models,Model, Neurological,Neurologic Model,Neurological Model,Neurological Models,Model, Neurologic,Models, Neurologic
D009435 Synaptic Transmission The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES. Neural Transmission,Neurotransmission,Transmission, Neural,Transmission, Synaptic
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D010749 Phosphoprotein Phosphatases A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992) Phosphoprotein Phosphatase,Phosphoprotein Phosphohydrolase,Protein Phosphatase,Protein Phosphatases,Casein Phosphatase,Ecto-Phosphoprotein Phosphatase,Nuclear Protein Phosphatase,Phosphohistone Phosphatase,Phosphoprotein Phosphatase-2C,Phosphoseryl-Protein Phosphatase,Protein Phosphatase C,Protein Phosphatase C-I,Protein Phosphatase C-II,Protein Phosphatase H-II,Protein-Serine-Threonine Phosphatase,Protein-Threonine Phosphatase,Serine-Threonine Phosphatase,Threonine Phosphatase,Ecto Phosphoprotein Phosphatase,Phosphatase C, Protein,Phosphatase C-I, Protein,Phosphatase C-II, Protein,Phosphatase H-II, Protein,Phosphatase, Casein,Phosphatase, Ecto-Phosphoprotein,Phosphatase, Nuclear Protein,Phosphatase, Phosphohistone,Phosphatase, Phosphoprotein,Phosphatase, Phosphoseryl-Protein,Phosphatase, Protein,Phosphatase, Protein-Serine-Threonine,Phosphatase, Protein-Threonine,Phosphatase, Serine-Threonine,Phosphatase, Threonine,Phosphatase-2C, Phosphoprotein,Phosphatases, Phosphoprotein,Phosphatases, Protein,Phosphohydrolase, Phosphoprotein,Phosphoprotein Phosphatase 2C,Phosphoseryl Protein Phosphatase,Protein Phosphatase C I,Protein Phosphatase C II,Protein Phosphatase H II,Protein Phosphatase, Nuclear,Protein Serine Threonine Phosphatase,Protein Threonine Phosphatase,Serine Threonine Phosphatase
D010750 Phosphoproteins Phosphoprotein
D011494 Protein Kinases A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. Protein Kinase,Kinase, Protein,Kinases, Protein
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002147 Calmodulin A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. Calcium-Dependent Activator Protein,Calcium-Dependent Regulator,Bovine Activator Protein,Cyclic AMP-Phosphodiesterase Activator,Phosphodiesterase Activating Factor,Phosphodiesterase Activator Protein,Phosphodiesterase Protein Activator,Regulator, Calcium-Dependent,AMP-Phosphodiesterase Activator, Cyclic,Activating Factor, Phosphodiesterase,Activator Protein, Bovine,Activator Protein, Calcium-Dependent,Activator Protein, Phosphodiesterase,Activator, Cyclic AMP-Phosphodiesterase,Activator, Phosphodiesterase Protein,Calcium Dependent Activator Protein,Calcium Dependent Regulator,Cyclic AMP Phosphodiesterase Activator,Factor, Phosphodiesterase Activating,Protein Activator, Phosphodiesterase,Protein, Bovine Activator,Protein, Calcium-Dependent Activator,Protein, Phosphodiesterase Activator,Regulator, Calcium Dependent
D003342 Corpus Striatum Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE. Lenticular Nucleus,Lentiform Nucleus,Lentiform Nuclei,Nucleus Lentiformis,Lentiformis, Nucleus,Nuclei, Lentiform,Nucleus, Lenticular,Nucleus, Lentiform,Striatum, Corpus
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine

Related Publications

R Kötter
February 2004, Proceedings of the National Academy of Sciences of the United States of America,
R Kötter
January 1997, Rossiiskii fiziologicheskii zhurnal imeni I.M. Sechenova,
Copied contents to your clipboard!