Simulation of dopamine modulation-based memory model

Abstract

Neurological electrophysiology has revealed that both dopamine and stimulation tend to affect the formation of memory. This study aimed to investigate the regulatory effect of dopamine and stimulation on long-term and short-term memories using an integrated striatal dopamine and neuronal network model. The robustness of the model was verified by applying interference stimulation. The results showed that the duration of network firing response was associated with the value of dopamine and the duration of stimulation, and the network firing peak was not affected by the interference stimulation, suggesting that the model was strongly robust.

Introduction

Memory is a psychological process of accumulating and preserving individual experiences in the brain. From the perspective of information processing, it is a process for the human brain to encode, store and retrieve the input information. Memory can explain a lot of problems, such as psychological problems of humans and patients with brain injury. And the capacity of memory plays an important role in the process of performing complex cognitive activities. People can use memory to store the information about the environment. This information is eventually used by human, so it is of great significance to study memory. According to the length of retention time, memory can be divided into transient, short-term and long-term. Transient memory refers to a memory in an extremely short time after the perception (such as one second or so), short-term memory refers to a memory in a relatively short time (less than one min) and long-term memory refers to a memory in a longer time (more than one min) [1], [2], [3]. Short-term and long-term memories are inter-related rather than mutually exclusive [4], [5]. Transformation of short-term memory to long-term memory relies on the transcription of cAMP-response element binding protein (CREB), which is a key regulatory molecule in the formation of long-term memory [6], [7]. Long-term potentiation (LTP) is also essential for the formation of memory. Formation and maintenance of LTP is a neural mechanism generated by pre-synaptic and post-synaptic combined effects, of which post-synaptic mechanism is dominant. The post-synaptic mechanism of LTP formation is closely related to the intracellular cascade after the activation of N-methyl-D-aspartic acid receptor (NMDA) [8], [9].

Several models have been proposed to describe the short-term memory(working memory) from different perspectives. For example, Reilly et al. [10] designed a working memory calculation model, which showed that the prefrontal cortex and basal ganglion were able to interact to complete a complex time expanding task, which was meant to maintain and update information by implementing a flexible working memory system with adaptive gating mechanism. The C-W model combined the recurrent neural network and the bistability of cells [11]. Another example is the ${\mathrm{Ca}}^{2+}$-based working memory model [12]. Some studies investigated the roles of basal ganglia and dopamine in the working memory [13]. However, very few models investigated the effects of dopamine on short-term and long-term memories as well as the interactions of these two types of memories during their formation process.

As is known to all, dopamine is a neurotransmitter, whose absence in the brain may cause tremor, rigidity, bradykinesia and other Parkinson׳s symptoms [14]. There have been many models that can be used to explain the electrophysiological data and the results associated with the dopamine modulation, such as computational models of schizophrenia and dopamine modulation in the prefrontal cortex [15], And the model which verified the importance of combined effects of dopamine in the basal ganglia and the prefrontal cortex [16]. And the study also showed that, dopamine was found to affect movements and also played an important role in memory [17], [18], [19]. Diego et al. [20] revealed that activation of dopamine D1 receptor promoted the formation of cortical LTP, which was conducive to the formation of long-term memory. Regulatory effect of dopamine on protein expression is essential for neuronal plasticity. Dudman et al. [21] demonstrated that the dopamine D1 receptors mediated CREB phosphonation through the phosphonation of NMDAs, indirectly indicating that these receptors affect the formation of long-term memory.

This study aimed to investigate the effects of dopamine on short-term and long-term memories by integrating striatal dopamine and neuronal network models as well as explore the effects of stimulation duration and interference stimulation (which refers to a second short stimulation during the delayed period) on the network firing.