Balanced Dopamine Is Critical for Pattern Completion during Associative Memory Recall

Abstract

Pattern completion, the ability to retrieve complete memories initiated by partial cues, is a critical feature of the memory process. However, little is known regarding the molecular and cellular mechanisms underlying this process. To study the role of dopamine in memory recall, we have analyzed dopamine transporter heterozygous knockout mice (DAT+/−), and found that while these mice possess normal learning, consolidation, and memory recall under full cue conditions, they exhibit specific deficits in pattern completion under partial cue condition. This form of memory recall deficit in the dopamine transporter heterozygous knockout mice can be reversed by a low dose of the dopamine antagonist haloperidol, further confirming that the inability to retrieve memory patterns is a result of dopamine imbalance. Therefore, our results reveal that a delicate control of the brain's dopamine level is critical for pattern completion during associative memory recall.

Object recognition impairment and rescue by a dopamine D2 antagonist in hyperdopaminergic mice

“…In addition, these heterozygous mice showed an increase in the exploration of objects placed in an open field [17], and in the frequency of object exploration [20]. DAT +/− mice showed impaired pattern completion in an environment with few spatial cues, which could be reversed by haloperidol [19]. However, no impairment of OR has been described [19,20].…”

“…Previous studies revealed that DAT +/− mice show impairment in pattern completion in a partial cue environment [19], and exhibit decreased anxiety-related behaviors [20]. The mild hyperdopaminergic DAT +/− mice present biochemical changes [18] related to memory impairment that could be reversed by D2 down regulation [19].…”

“…Yet, in addition to neurochemical alterations leading to a mild DA increase at the synaptic level, only a handful of studies have described memory alterations in DAT +/− mice [19,20]. Previous studies revealed that DAT +/− mice show impairment in pattern completion in a partial cue environment [19], and exhibit decreased anxiety-related behaviors [20].…”

“…In contrast, only a few studies have been published on DAT +/− mice, a mild model of hyperdopaminergia. In this model, a mild disbalance of dopamine results in several cognitive changes [17,19,20]. DAT +/− mice exhibit less immobility time during the forced swimming test [17], higher time spent in the center of an open field [20], and more time spent in the open arms in comparison to WT mice in a plus maze [19] or zero maze [20].…”

“…In this model, a mild disbalance of dopamine results in several cognitive changes [17,19,20]. DAT +/− mice exhibit less immobility time during the forced swimming test [17], higher time spent in the center of an open field [20], and more time spent in the open arms in comparison to WT mice in a plus maze [19] or zero maze [20]. In addition, these heterozygous mice showed an increase in the exploration of objects placed in an open field [17], and in the frequency of object exploration [20].…”