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Spontaneous and artificial lesions of magnocellular reticular formation of brainstem deteriorate avoidance learning
1Department of Neurology, Faculty of Medicine, Kyoto University, Kyoto, Japan.
Abstract:
The role of the magnocellular reticular formation (MGRF) of the brainstem on learning and memory was examined in memory-deficient mice with spontaneous spongy degeneration in the brainstem (senescence-accelerated mouse, SAMP8) and control mice (accelerated-senescence resistant mouse, SAMR 1). SAMP8 showed spontaneous age-related impairment of learning and memory, as determined by passive and active avoidance responses. The deficits of learning and memory function in passive avoidance performances began at two months of age and increased with ageing. In the brains of SAMP8 at one month of age and older, spongy degeneration was mainly observed in the brainstem, while no vacuoles were evident in SAMR1 control (normal ageing mouse) brains in the age range tested (up to 12 months). The vacuolization in SAMP8 was marked in the MGRF, especially in the dorsomedial MGRF. Quantitative analysis of the vacuolization showed that the total area and number of vacuoles in the MGRF increased with age, and they were affected by the degree of deficits in learning and memory. The latency 24 h after footshock in passive avoidance tests decreased with the increase in total area and number of vacuoles in MGRF. The number of shocks in active avoidance tests increased with the increase in total number and area of vacuoles. Thus, learning and memory ability in passive and active avoidance responses deteriorated with enlargement in the vacuolated area in MGRF, and it was assumed that MGRF (especially, the dorsomedial part) possesses functions related to learning and memory. To confirm this notion, behavior and memory tests (passive avoidance and active avoidance tests, open field tests and shock sensitivity measurements) were carried out in SAMR1 mice, whose bilateral dorsomedial MGRF was destroyed electrolytically (MGRF-lesioned mice). The MGRF-lesioned mice showed no difference from sham mice in sensory threshold or open field activity; however, there was severe deterioration in passive avoidance behavior and impairment in the active avoidance performances. From the results in SAMP8 and MGRF-lesioned mice, it was confirmed that MGRF (especially the dorsomedial part) has functions related to learning and memory, and is one part in the learning and memory system of the brain. Thus, SAMP8 can serve as a model of RF-lesioned mice with impaired learning and memory functions.
Insights
The magnocellular reticular formation (MGRF) in the brainstem is crucial for learning and memory. Damage to the MGRF in mice significantly impairs these cognitive functions, highlighting its role in memory systems.
Area of Science:
- Neuroscience
- Cognitive Science
- Aging Research
Background:
- Spongy degeneration in the brainstem of senescence-accelerated mouse (SAMP8) mice leads to age-related learning and memory deficits.
- Vacuolization, particularly in the magnocellular reticular formation (MGRF), correlates with memory impairment in SAMP8 mice.
Purpose of the Study:
- To investigate the role of the MGRF in learning and memory.
- To validate the SAMP8 mouse as a model for studying MGRF-related cognitive decline.
Main Methods:
- Comparative behavioral analysis of SAMP8 and control SAMR1 mice using passive and active avoidance tests.
- Histological examination of brainstem vacuolization in both mouse strains.
- Electrolytic lesioning of the dorsomedial MGRF in SAMR1 mice followed by behavioral testing.
Main Results:
- SAMP8 mice exhibited progressive learning and memory deficits correlated with MGRF vacuolization.
- MGRF-lesioned mice showed significant impairment in passive and active avoidance behaviors compared to sham controls.
- No significant differences were observed in sensory thresholds or open field activity between lesioned and sham mice.
Conclusions:
- The MGRF, especially its dorsomedial part, plays a critical role in learning and memory functions.
- SAMP8 mice serve as a valid model for studying the impact of MGRF dysfunction on cognitive abilities.
- These findings contribute to understanding the neural basis of learning and memory within the brainstem circuitry.