LAUSR

HighlightsD1/D5 receptor‐dependent LTP (DA‐LTP) in CA1 region is MEK/MAPK pathway dependent.Here we studied the differential role of CaMKs and MEKs during DA‐LTP.With weak dopaminergic activation, both CaMKII and MEKs were necessary for DA‐LTP.During stronger dopaminergic activation, the role of CaMKII becomes dispensable.MEK/MAPK activation is crucial both during weaker and stronger activation of DA‐LTP. Abstract Dopaminergic neurotransmission modulates and influences hippocampal CA1 synaptic plasticity, learning and long‐term memory mechanisms. Investigating the mechanisms involved in the slow‐onset potentiation induced by the dopamine D1/D5 receptor agonists in hippocampal CA1 region, we have reported recently that it could play a role in regulating synaptic cooperation and competition. We have also shown that a sustained activation of MEK/MAP kinase pathway was involved in the maintenance of this long‐lasting potentiation (Shivarama Shetty, Gopinadhan, & Sajikumar, 2016). However, the molecular aspects of the induction of dopaminergic slow‐onset potentiation are not known. Here, we investigated the involvement of MEK/MAPK pathway and Ca2+‐calmodulin‐dependent protein kinases (CaMKII and CaMKIV) in the induction and maintenance phases of the D1/D5 receptor‐mediated slow‐onset potentiation. We report differential involvement of these kinases in a dose‐dependent manner wherein at weaker levels of dopaminergic activation, both CaMKII and MEK1/2 activation is necessary for the establishment of potentiation and with sufficiently stronger dopaminergic activation, the role of CaMKII becomes dispensable whereas MEK activation remains crucial for the long‐lasting potentiation. The results are interesting in view of the involvement of the hippocampal dopaminergic system in a variety of cognitive abilities including memory formation and also in neurological diseases such as Alzheimer’s disease and Parkinson’s disease.