Glutamate transporters, found on both neurons and glia, differ in their regional and cellular distribution, as well as their pharmacological and biophysical properties. EAAT2, found on glia, is responsible for over 90% of glutamate uptake from the extracellular space. Glutamate taken up by glial cells is converted to glutamine and transported back into the presynaptic terminal. Inside the presynaptic terminal, glutamate is packaged into synaptic vesicles by vGLUTs, which are present in the membrane of glutamatergic vesicles. The transport of glutamate into synaptic vesicles by vGLUT is driven by the countertransport of H+ ions. Nerve cells in the CNS that use biogenic amines as neurotransmitters are primarily found in brainstem nuclei. Noradrenergic neurons are mainly found in the locus coeruleus and nucleus subcoeruleus. Serotoninergic fibers arise from raphe nuclei. Dopaminergic fibers arise from the substantia nigra pars compacta and the ventral tegmental area. Histaminergic neurons are located in the tuberomammillary nucleus. Adrenergic neurons are localized to small cell groups in the rostral medulla. These aminergic systems are involved in setting global brain states and have important homeostatic functions. Dopamine plays a role in balancing the flow of activity through the basal ganglia pathways and its loss is associated with the motor symptoms of Parkinson's disease.
Fig.6.11B ).Inaddition,thetransporterhasCl− conductance,althoughpassageofCl− ionsisnotstoichiometricallylinkedtoglutamatetransport.Glutamatetransportersarefoundonbothneuronsandglia.However,thetransportersdifferintheirregionalandcellulardistributionandintheirpharmacologicalandbiophysicalproperties.Forexample,EAAT2isfoundongliaandisgenerallyresponsibleformorethan90%ofglutamateuptakefromtheextracellularspace.TheglutamatetakenupintoglialcellsbyEAAT2iseventuallyreturnedtothepresynapticterminalbytheglutamateglutaminecycle(see
Fig.6.11 ).Insideglialcells,glutamateisconvertedtoglutamine.Glutamineisthentransportedoutoftheglialcellandbackintothepresynapticterminal,whereitissubsequentlyconvertedbacktoglutamate.GlutamateinsidethepresynapticterminalispackagedintosynapticvesiclesbyasecondsetofglutamatetransportersknownasvGLUTs (vesicular glutamate transporters),whicharepresentinthemembraneofglutamatergicvesicles.TransportofglutamateintosynapticvesiclesbyvGLUTisdrivenbythecountertransportofH+ ions,theelectrochemicalgradientforwhichhavingbeenestablishedbyanH+-ATPaseinthevesiclemembrane.
Within the CNS, nerve cells that use biogenic amines as neurotransmitters are primarily found within one of a few brainstem nuclei, most of which project rather diffusely throughout large areas of the brain. Noradrenergic neurons are primarily found in the locus coeruleus and nucleus subcoeruleus, which are located near each other in the dorsal part of the rostral pons. The neurons of the locus coeruleus project throughout the entire brain. Targets of the nucleus subcoeruleus are more limited but still widespread and include the pons, medulla, and spinal cord. (Norepinephrine is also important in the peripheral nervous system because it is used by postganglionic sympathetic cells.) Serotoninergic fibers arise from a series of nuclei located at the midline of the brainstem, known as the raphe nuclei. Similar to the noradrenergic fibers, serotoninergic fibers are distributed throughout most of the brain and spinal cord. Dopaminergic fibers arise from two main brainstem regions: the substantia nigra pars compacta, which projects to the striatum, and the ventral tegmental area, which projects more widely to the neocortex and subcortical areas, including the nucleus accumbens. Histaminergic neurons are located within the tuberomammillary nucleus of the hypothalamus and project diffusely throughout the CNS. Finally, adrenergic neurons are relatively few in number when compared with the other biogenic amine transmitters. They have cell bodies localized to small cell groups in the rostral medulla. The largest group, termed C1, has projections to the locus coeruleus and down to the thoracic and lumbar levels of the spinal cord, where they terminate in the autonomic nuclei of the intermediolateral and intermediomedial cell columns. Thus, these neurons are important for autonomic functions, particularly vasomotor ones, such as control of arterial pressure.
The diffuse nature of the projection pattern of most of the amine systems is mirrored in their proposed functions. Activity in the different aminergic systems is believed to be important in setting global brain states. For example, these systems are involved in setting the level of arousal (sleep, waking), attention, and mood. Their involvement in pathways connected with the hypothalamus and other autonomic centers also indicates that they have important homeostatic functions. The role of dopamine in balancing the flow of activity through the basal ganglia pathways and how its loss leads to the motor symptoms observed in Parkinson’s disease are described in