Presence of NMDA-type glutamate receptors in cingulate corticostriatal terminals and their postsynaptic targets

Abstract

The glutamatergic projection from the anterior cingulate cortex to the medial caudate-putamen nucleus (CPN) has been implicated in motor and cognitive functions, many of which are potently modulated by activation of N-methyl-D-aspartate subtype of glutamate receptors (NMDARs). To determine the functional sites for NMDAR activation within this circuitry, we combined anterograde transport of biotinylated dextran amine (BDA) from deep layers of the rat anterior cingulate cortex with immunogold labeling of NMDAR subunit, NMDAR1, in the dorsomedial CPN. BDA-containing axons were seen in patch-like clusters in a neuropil that showed more uniform immunogold-silver labeling for NMDAR1. Electron microscopy of these regions showed that BDA-labeling was present exclusively in axons and terminals, 23% (98 of 421) of which also contained NMDAR1-immunoreactivity (IR). BDA-labeled terminals often apposed NMDAR1-immunoreactive neuronal and glial profiles. These terminals also formed asymmetric excitatory-type synapses with dendritic spines. Of 155 anterogradely labeled axon terminals forming asymmetric synapses, 34% were with NMDAR1-labeled, and 66% with unlabeled dendritic spines. These results provide ultrastructural evidence for the involvement of NMDARs in presynaptic regulation of glutamate transmission, and in postsynaptic modulation of the excitability of spiny neurons in patch-like compartments of the dorsomedial CPN. These dual NMDAR-mediated actions are likely to play a major role in the acquisition of new behaviors and reward-related processes that have been associated with cortical input to the striatal patch compartments.

The Metabotropic Glutamate 5 Receptor Antagonist 3-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]-pyridine Reduces Ethanol Self-Administration in Multiple Strains of Alcohol-Preferring Rats and Regulates Olfactory Glutamatergic Systems

“…5, C and F). It is noteworthy that these changes in glutamate receptor expression occurred predominantly in olfactory-associated nuclei and also within the cingulate cortex, which provides excitatory input to the basal ganglia (Wang and Pickel, 2000). Therefore, we next analyzed markers of the dopaminergic system and found that 12 days of treatment with MTEP led to a significant increase in DAT binding (ϩ9%, t 74 ϭ 2.691, p ϭ 0.0088; Fig.…”

Prenatal Stress Enhances Responsiveness to Cocaine

“…Decreased basal NAC glutamate levels and enhanced cocaine-stimulated glutamate release are neuroadaptations observed following repeated contingent or noncontingent cocaine administration (for reviews see Anderson and Pierce, 2005;Cornish and Kalivas, 2001;Vandershuren and Kalivas, 2000). PNS has been associated with increased NAC N-methyl-D-aspartate (NMDA) receptor expression Berger et al, 2002), which are found presynaptically on corticostriatal terminals (Gracy and Pickel, 1996;Wang and Pickel, 2000). Given that the majority of cortical inputs to the striatum are glutamatergic, increased numbers of presynaptically localized NMDA receptors could result in glutamate enhancing its own release and contribute to the phenotype of PNS.…”

Glutamate and GABA receptors and transporters in the basal ganglia: What does their subsynaptic localization reveal about their function?

“…Only scarce presynaptic NR1 or NR2A immunoreactivity is observed in the striatum (Bernard and Bolam, 1998;Fujiyama et al, 2004) (but see Wang and Pickel, 2000). Nevertheless, physiological studies indicate that striatal NMDA receptors are involved in the regulation of dopamine and glutamate release (e. g. Krebs et al, 1991;Micheletti et al, 1993;Morari et al, 1993;Cheramy et al, 1996;Sesack et al, 2003).…”