Spatial learning-induced accumulation of agmatine and glutamate at hippocampal CA1 synaptic terminals

Agmatine, the decarboxylated metabolite of l-arginine, is considered to be a novel putative neurotransmitter. Recent studies have demonstrated that endogenous agmatine may directly participate in the processes of spatial learning and memory. Agmatine-immunoreactivity has been observed within synaptic terminals of asymmetric excitatory synapses in the hippocampal CA1 stratum radiatum (SR), suggesting that agmatine may be colocalized with glutamate. In the present study we demonstrate, using immunofluorescence confocal microscopy, that agmatine is colocalized with glutamate within CA1-CA3 hippocampal pyramidal cell bodies, in young Sprague-Dawley rats. Subcellular investigation, using postembedding electron microscopy-immunogold cytochemistry, has also revealed that agmatine is colocalized with glutamate in most synaptic terminals in the SR region of CA1. Ninety-seven percent of all agmatinergic profiles were found to contain glutamate, and 92% of all glutamatergic profiles contained agmatine (n=6; 300 terminals). Alterations in colocalized agmatine and glutamate levels in the SR synaptic terminals, following 4 days Morris water maze training, were also investigated. Compared with swim only control rats, water maze-trained rats had statistically significant increases in both agmatine (78%; P<0.01) and glutamate (41%; P<0.05) levels within SR terminals synapsing onto CA1 dendrites. These findings provide the first evidence that agmatine and glutamate are colocalized in synaptic terminals in the hippocampal CA1 region, and may co-participate in spatial learning and memory processing.