Effect of Motor and Premotor Cortex Ablation on Concentrations of Amino Acids, Monoamines, and Acetylcholine and on the Ultrastructure in Rat Striatum. A Confirmation of Glutamate as the Specific Cortico‐Striatal Transmitter

Abstract

At 1, 2, and 4 weeks after unilateral premotor and motor cortex ablation in rats, a significant and lasting decrease in glutamate levels in the ipsilateral versus contralateral striatum was observed. A significant corresponding fall in aspartate was seen only after 1 week. In contrast, there was a large increase in the striatal concentrations of lysine, threonine, alanine, and glutamine 1 week after the cortical ablation. This correlates with the extensive glial proliferation in the deafferented ipsilateral striatum. Four weeks after cortical ablation the GABA concentration was significantly increased. There was no decrease in other putative transmitters (dopamine, serotonin, acetylcholine, glycine and taurine), nor was a glutamate decrease observed in the hippocampus or in the hypothalamus, which do not receive direct premotor and motor cortical inputs. Both biochemical and morphological evidence for a minor contralateral cortico-striatal projection was obtained. Correlating with the fall in glutamate, ultrastructural observations indicated the degeneration of two types of striatal synapses, i.e., those of the axo-spinous type III and of the axo-dendritic type VII. Frontal cortex ablation clearly affects, in opposite directions, the metabolism of various striatal amino acids but not that of acetylcholine and the monoamine transmitters. The results strongly support the view that glutamate is the transmitter of the cortico-striatal fibers.

Distinct changes in neuronal and astrocytic amino acid neurotransmitter metabolism in mice with reduced numbers of synaptic vesicles

“…The apparent unaffected glutamate levels and metabolism in cerebrum extracts of synapsin DKO mice may, however, be explained by the many roles and widespread distribution of glutamate in the brain, compared to GABA. Lesion-induced destruction of pre-synaptic glutamatergic structures previously demonstrated a 15-30% reduction in glutamate levels in several target areas, and these reductions were suggested to represent the size of the neurotransmitter pool in glutamatergic neurons (Karlsen and Fonnum 1978;Walaas and Fonnum 1980;Hassler et al 1982). Moreover, since a considerable amount of presynaptic glutamate is localized in mitochondria (Shupliakov et al 1992), it appears likely that the transmitter pool of glutamate measured by lesions could represent an overestimate.…”

NMDA receptors in the basal ganglia

“…Recent studies suggest that the intralaminar nuclei exert a prominent synaptic control over the cholinergic interneurons of the rat dorsal striatum (Lapper & Bolam, 1992), via NMDA receptors (Baldi et al 1995). These pathways utilise glutamate as their transmitter (Hassler et al 1982 ;Errami & Nieoullon, 1986 ;Spencer, 1986 ;Bevan et al 1995 ;Consolo et al 1996 a, b).…”

Increase of Extracellular Glutamate and Expression of Fos‐Like Immunoreactivity in the Ventral Tegmental Area in Response to Electrical Stimulation of the Prefrontal Cortex

“…The PFC fibers make asymmetric, presumably excitatory, monosynaptic contacts on dopaminergic and nondopaminergic VTA neurons (Sesack and Pickel, 1992). Excitatory amino acids are the primary neurotransmitters of cortical efferents (Spencer, 1976;McGeer et al, 1977;Fonnum et al, 1981;Hassler et al, 1982;Christie, 1985;Girault et al, 1986;Young and Bradford, 1986), and the local application of exogenous excitatory amino acids to the VTA, either in vivo or in vitro, activates dopamine neurons (Grenhoff et al, 1988a;French and Ceci, 1990;Johnson et al, 1992;Suaud-Chagny et aI., 1992;Chergui et al, 1993;Mercuri et al, 1993;Wang and French, 1993a) and increases dopamine release in the nucleus accumbens septi (NAS) (Kalivas et al, 1989;Wang et al, 1994;Westerink et al, 1996). Electrical stimulation of the PFC increases the activity of dopaminergic VTA cells , induces burst firing (Gariano and Groves, 1988;Murase et al, 1993;Chergui et al, 1994;Tong et al, 1996a,b), and increases dopamine release in terminal fields including the NAS (Nieoullon et al, 1978;Murase et al, 1993;Fibiger, 1993, 1995;.…”