A known selective agonist of the A 3 adenosine receptors (AR), MRS1898 [(1′R,2′R,3′S,4′R,5′S)-4-{2-chloro-6-[(3-iodophenylmethyl)amino]purin-9-yl}-1-(methylaminocarbonyl)bicyclo[3.1.0]hexane-2,3-diol], was synthesized in radioactive form and characterized pharmacologically. This agonist ligand series, based on nucleoside analogues containing a rigid, bicyclic ring system in place of the ribose moiety, was selected for radiolabeling due to its high A 3 AR affinity across species, with nanomolar binding at both rat and human A 3 ARs. The radioiodination of MRS1898 on its N 6 -3-iodobenzyl substituent was accomplished in 76% radiochemical yield by iododestannylation of a 3-(trimethylstannyl)benzyl precursor. ]MRS1898 compared with previously used radioligands are primarily its high selectivity and affinity for the rat A 3 AR and also its facile synthesis and radiochemical stability; however, a relatively high level of nonspecific binding presents a limitation. Thus, we have introduced the first selective radioligand for the rat A 3 AR.
The primate brain is equipped to learn and remember newly encountered visual stimuli such as faces and objects. In the macaque inferior temporal (IT) cortex, neurons mark the familiarity of a visual stimulus through response modification, often involving a decrease in spiking rate. Here, we investigate the emergence of this neural plasticity by longitudinally tracking IT neurons during several weeks of familiarization with face images. We found that most neurons in the anterior medial (AM) face patch exhibited a gradual decline in their late-phase visual responses to multiple stimuli. Individual neurons varied from days to weeks in their rates of plasticity, with time constants determined by the number of days of exposure rather than the cumulative number of presentations. We postulate that the sequential recruitment of neurons with experience-modified responses may provide an internal and graded measure of familiarity strength, which is a key mnemonic component of visual recognition.
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