Antagonism of D1/D5 receptors prevents long-term depression (LTD) and learning-facilitated LTD at the perforant path-dentate gyrus synapse in freely behaving rats

Abstract

Hippocampal synaptic plasticity, in the form of long-term potentiation (LTP) and long-term depression (LTD), enables spatial memory formation, whereby LTP and LTD are likely to contribute different elements to the resulting spatial representation. Dopamine, released from the ventral tegmental area particularly under conditions of reward, acts on the hippocampus, and may specifically influence the encoding of information into long-term memory. The dentate gyrus (DG), as the "gateway" to the hippocampus is likely to play an important role in this process. D1/D5 dopamine receptors are importantly involved in the regulation of synaptic plasticity thresholds in the CA1 region of the hippocampus and determine the direction of change in synaptic strength that occurs during novel spatial learning. Here, we explored whether D1/D5-receptors influence LTD that is induced in the DG following patterned afferent stimulation of the perforant path of freely behaving adult rats, or influence LTD that occurs in association with spatial learning. We found that LTD that is induced by afferent stimulation, and LTD that is facilitated by learning about novel landmark configurations, were both prevented by D1/D5-receptor antagonism, whereas agonist activation of the D1/D5-receptor had no effect on basal tonus or short-term depression. Other studies have reported that in the DG, D1/D5-receptor agonism or antagonism do not affect LTP, but agonism prevents depotentiation. These findings suggest that the dopaminergic system, acting via D1/D5-receptors, influences information gating by the DG and modulates the direction of change in synaptic strength that underlies information storage in this hippocampal substructure. Information encoded by robust forms of LTD is especially dependent on D1/D5-receptor activation. Thus, dopamine acting on D1/D5-receptors is likely to support specific experience-dependent encoding, and may influence the content of hippocampal representations of experience.

Keywords: dopamine; hippocampus; rodent; spatial learning; synaptic plasticity.