The contribution of dopamine to the functioning of the hippocampus during spatial learning (a hypothetical mechanism)

Abstract

A hypothetical mechanism for the influence of dopamine on the formation of neuronal representations of “object–place” associations in the hippocampus is proposed for spatial learning. According to this mechanism, dopamine that is released in a new situation or during expectation of reinforcement improves conditions for the development of homosynaptic long-term potentiation (LTP) of the input to the dentate gyrus granule cells from the medial entorhinal cortex, which transmits information about spatial location of objects and characteristics of objects. The effect occurs due to the activation of D1/D5 receptors on granule cells and D2 receptors on inhibitory interneurons. Heterosynaptic depression is simultaneously developed in inputs that were not activated. As a result, a contrasting representation of the learned “object–place” association is formed on neurons of the dentate gyrus. From these neurons, information about the association via the CA3 field is transmitted to the radial layer of the CA1 field by Schaffer collaterals, whereas the stratum lacunosum-moleculare receives signals directly from the entorhinal cortex and thalamic nucleus reuniens, which connects the hippocampus with the prefrontal cortex. The sign of the modulatory influence of dopamine on the efficacy of excitatory inputs to pyramid neurons of the CA1 field depends on the relationship between excitation and inhibition of these neurons, as well as the dopamine concentration. By acting on D1/D5 receptors on the pyramidal neurons of the CA1 field, dopamine can promote LTP induction in Schaffer collaterals simultaneously with LTP induction in the relatively strong perforant input, whereas relatively weak perforant input, as well as the input from the nucleus reuniens, become depressed. This depression is promoted by the activation of D1/D5 receptors on the inhibitory interneurons of the CA1 field, induction of LTP in these neurons, and the following enhancement of afferent inhibition of pyramidal cells. As a consequence, neuronal representation of the learned “object–place” association in the CA1 field is distorted more weakly by non-relevant information that comes from the entorhinal cortex and thalamus. As a result, the error probability during the performance of spatial task decreases. Because activation of D1/D5 receptors on pyramidal neurons of the prefrontal cortex promotes LTP induction in the input from the CA1 field, dopamine must improve the goal-directed performance of spatial tasks. The proposed mechanism explains the results of some experimental studies that seemed to be contradictory or incomprehensible.