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Updated: Aug 25, 2026
Ex Vivo Imaging of Postnatal Cerebellar Granule Cell Migration Using Confocal Macroscopy
Published on: May 12, 2015
Displaced granule cells in the molecular layer of the cerebellar cortex in mice treated with methylazoxymethanol
Hajime Yamanaka1, Kunihiko Obata
1Neuronal Network Mechanisms Research Group, RIKEN Brain Science Institute, Wako, Saitama, Japan.
Abstract:
To study the effect of a reduced granule cell number on the development of the cerebellum, mice were administered with methylazoxymethanol (MAM) at birth and examined histologically at 21 days of age. In these mice, green fluorescent protein had been knocked in within the glutamic acid decarboxylase 67 gene, resulting in fluorescent GABAergic neurons. In severe cases, granule cells were greatly reduced in number and mixed with Purkinje cells instead of forming layers. In about 10% of the MAM-treated mice, an ectopic cell layer consisting of granule cells was observed within the molecular layer. Concomitantly, basket cells disappeared. The transient interruption of granule cell production in the external granular layer presumably resulted in their incomplete migration through the molecular layer.
Insights
Methylazoxymethanol (MAM) exposure in mice disrupts cerebellar development, causing reduced granule cells and altered neuronal organization. This highlights the critical role of granule cell development in cerebellar structure.
Area of Science:
- Neuroscience
- Developmental Biology
- Histology
Background:
- Cerebellar granule cells are crucial for motor control and cognitive functions.
- Disruptions in cerebellar development can lead to neurological disorders.
- Understanding the impact of early-life insults on cerebellar circuitry is vital.
Purpose of the Study:
- To investigate the effects of methylazoxymethanol (MAM) on cerebellar granule cell development.
- To analyze the histological consequences of reduced granule cell numbers.
- To understand the migration patterns and cellular organization in the developing cerebellum.
Main Methods:
- Administration of methylazoxymethanol (MAM) to neonatal mice.
- Histological examination of cerebellar tissue at 21 days of age.
- Utilizing mice with green fluorescent protein knocked into the glutamic acid decarboxylase 67 gene for visualizing GABAergic neurons.
Main Results:
- Severe reduction in cerebellar granule cell numbers observed in MAM-treated mice.
- Granule cells were found intermixed with Purkinje cells, disrupting normal layering.
- Ectopic granule cell layers formed within the molecular layer in approximately 10% of treated mice.
- Concomitant disappearance of basket cells was noted.
Conclusions:
- Transient interruption of granule cell production by MAM likely impairs their migration.
- Altered cerebellar cell organization results from disrupted granule cell development.
- MAM-induced neurodevelopmental changes offer insights into cerebellar circuit formation and potential pathologies.
