Excitatory Amino Acid Neurotransmitters in the Corticostriate Pathway: Studies Using Intracerebral Microdialysis In Vivo

Abstract

The concentration of extracellular excitatory amino acids in the striatum of conscious, unrestrained rats was measured using intracerebral microdialysis, during chemical stimulation of the striatum in intact and hemidecorticate animals. Chemical stimulation of the striatum with tityustoxin (0.1 microM) evoked a rise in dialysate concentration of glutamate (to 383% of basal) and aspartate (to 156% of basal), accompanied by a drop in glutamine (to 55% of basal). These changes showed significant attenuation after treatment with L-proline (1 mM) or 2-chloroadenosine (15 microM). Unilateral degeneration of the corticostriate pathway, produced by frontal hemidecortication, caused a reduction in both basal and stimulated levels of glutamate in the lesioned side, whereas no effect was observed in the intact side. Similarly, basal and stimulated levels of glutamine were unchanged in the intact side, but were increased in the lesioned side. These results provide in vivo evidence for glutamate and possibly aspartate being neurotransmitters in the corticostriate pathway. In addition they lend support to previous studies in vitro, which implicated glutamine as the principal precursor for neurotransmitter glutamate.

Brain microdialysis of GABA and glutamate: What does it signify?

“…Another method that has been used to elucidate the neuronal contribution to extracellular amino-acid levels is the lesioning of specific glutamatergic or GABAergic pathways and measurement of basal extracellular glutamate or GABA levels, respectively, in the brain structures where the axons of these neurons terminate (Young and Bradford, 1986;Herrera-Marschitz et al, 1992;Campbell et al, 1993a). Indeed, significant decreases in extracellular glutamate and GABA levels in the denervated structures compared to the levels in intact structures have been found.…”

Coincident Activation of NMDA and Dopamine D1Receptors within the Nucleus Accumbens Core Is Required for Appetitive Instrumental Learning

“…The nucleus accumbens, a forebrain structure known to subserve behaviors governed by natural reinforcers, receives excitatory glutamatergic input from prefrontal cortex, hippocampus, thalamus, and amygdala (McGeer et al, 1977;Walaas and Fonnum, 1979;Young and Bradford, 1986;Fuller et al, 1987;Robinson and Beart, 1988), as well as a major dopaminergic innervation from the ventral tegmental area (Lindvall and Bjorklund, 1978). These innervations converge on the dendritic spines of the medium spiny neurons that populate the nucleus accumbens (Totterdell and Smith, 1989;Sesack and Pickel, 1990;Smith and Bolam, 1990).…”

N‐Methyl‐d‐Aspartate Releases γ‐Aminobutyric Acid from Rat Striatum In Vivo: A Microdialysis Study Using a Novel Preloading Method

“…Glutamate and possibly aspartate are important excitatory transmitters in the cortical fibres innervating this region (McGeer et al, 1977;Fonnum et al, 198 1;Young and Bradford, 1986;Butcher and Hamberger, 1987), whereas the inhibitory amino acid y-aminobutyric acid (GABA) appears to be the major transmitter in the striatonigral and stnatopallidal pathways, as well as in certain intrinsic neurones (Schwarcz and Coyle, 1977;Fonnum et al, 1978;Ribak et al, 1979;Butcher and Hamberger, 1987). There are at least three different subtypes of excitatory amino acid receptor in the brain, characterised by their preferential activation by the agonists N-methyl-D-aspartate (NMDA), kainate, and quisqualate (Watkins and Evans, 198 1;McLennan, 1983), and autoradiographic studies have shown that all three subtypes are present in the stnatum (Cotman et al, 1987).…”