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Effects of the mGluR2/3 agonist LY354740 on computerized tasks of attention and working memory in marmoset monkeys
Simona Spinelli1, Theresa Ballard, Silvia Gatti-McArthur
1Behavioural Neurobiology Laboratory, Swiss Federal Institute of Technology Zurich, Schorenstrasse 16, 8603 Schwerzenbach, Switzerland.
Rationale:
LY354740 is a recently developed metabotropic glutamatergic receptor 2 and 3 (mGluR2/3) agonist. A high density of mGluR2 has been reported in terminal fields of the perforant path in rodents and humans, suggesting its involvement in cognitive functions mediated by the temporal lobe, including memory. A small number of in vivo studies in rodents have assessed the effects of LY354740 on memory tasks, reporting the induction of impaired memory for spatial orientation in a water maze task and for delayed match and non-match to position in an operant version of these tasks.
Objective:
In the present primate study, we used radioautography to describe the distribution and intensity of (3)H-LY354740 binding in the hippocampal formation of the common marmoset monkey (Callithrix jacchus) relative to the rat. In the major, in vivo part of the study, the effects of systemic LY354740 on computerized tasks of attention and memory were investigated.
Methods:
Adult common marmosets were trained to perform a five-choice serial reaction time (5-CSRT) task and a concurrent delayed match-to-position (CDMP) task from the Cambridge Neuropsychological Automated test Battery (CANTAB). Filter tests of LY354740 effects on motor dexterity and motivation for reward revealed high inter-individual variation in sensitivity; therefore, on the 5-CSRT, subjects were tested at a dose range of 3--10 mg/kg, and on the CDMP, subjects were tested at 1--3 or 3--10 mg/kg.
Results:
Radioautography revealed a relatively low level of (3)H-LY354740 binding in the marmoset hippocampal formation compared to the rat. Despite low binding, LY354740 reduced sustained-attention accuracy in the 5-CSRT, and reduced accuracy in two stages of the CDMP.
Conclusions:
The current study provides novel evidence for the importance of mGluR2/3 in the regulation of primate cognitive functioning.
Insights
Metabotropic glutamatergic receptor 2/3 (mGluR2/3) agonist LY354740 impaired attention and memory in marmosets, despite low binding in the hippocampus. This highlights the role of mGluR2/3 in primate cognitive functions.
Area of Science:
- Neuroscience
- Cognitive Science
- Pharmacology
Background:
- Metabotropic glutamatergic receptor 2 and 3 (mGluR2/3) agonists, like LY354740, are implicated in cognitive functions.
- Previous rodent studies suggest LY354740 may impair memory.
- mGluR2 receptors are abundant in brain regions associated with memory, such as the temporal lobe.
Purpose of the Study:
- To map the distribution of (3)H-LY354740 binding in the marmoset hippocampal formation.
- To investigate the effects of systemic LY354740 on attention and memory in common marmosets using computerized tasks.
Main Methods:
- Radioautography was used to determine (3)H-LY354740 binding patterns in marmoset hippocampus.
- Common marmosets were trained on the five-choice serial reaction time (5-CSRT) and concurrent delayed match-to-position (CDMP) tasks.
- LY354740 was administered systemically at various doses to assess its effects on cognitive performance.
Main Results:
- (3)H-LY354740 binding was relatively low in the marmoset hippocampus compared to rats.
- Despite low binding, LY354740 significantly reduced sustained attention accuracy on the 5-CSRT task.
- LY354740 also impaired accuracy in two key stages of the CDMP task.
Conclusions:
- The study demonstrates that mGluR2/3 agonists impact primate cognitive functions, specifically attention and memory.
- These findings underscore the importance of the mGluR2/3 system in regulating cognitive processes in primates.
- The results suggest potential therapeutic targets for cognitive disorders involving mGluR2/3 pathways.
