Behavioral Tagging: Role of Neurotransmitter Receptor Systems in Novel Object Recognition Long-Term Memory

[Image: see text] Strong training is known to form long-term memory (LTM) as it is an inducer for both a learning tag (just like a synaptic tag/molecular tag) and plasticity-related proteins (PRPs), while weak training is an inducer of only a learning tag. However, weak training can also lead to LTM if paired with another behavioral task (open field in our study—a representative of a novel environment) around the time of PRP arrival. Weak behavioral training is a learning tag inducer, while the open field is a PRP inducer. The learning tag then captures these PRPs to form LTM. This is the basis of behavioral tagging (BT). BT is a well-known model for the evaluation of a few learning and memory forms. In this work, we examined the role of glutamate and D1/D5 (dopamine) receptors in the synthesis of a novel object recognition (NOR) tag (learning) as well as in PRP arrival, which come together to form NOR-LTM. Employing antagonists and/or agonists preceding or proceeding the open field and/or NOR training, it was revealed that the activation/stimulation of D1/D5 (dopamine) receptors and glutamatergic NMDA receptors plays a critical part in PRP arrival. We found that the activation/stimulation of NMDA receptors also contributes to the setting of the learning tag. Moreover, changes in glutamate, dopamine, and GABA neurotransmitter levels were also analyzed. These findings thus demonstrate the critical time window required for NOR-LTM formation based on the process of BT along with the role of activation/stimulation of D1/D5 (dopamine) receptors and NMDA receptors in the arrival of PRPs and learning tags for NOR-LTM formation.