Related Experiment Video
Updated: Jul 14, 2026
T-maze Forced Alternation and Left-right Discrimination Tasks for Assessing Working and Reference Memory in Mice
Published on: February 26, 2012
Motor and cognitive deficits in the heterozygous leaner mouse, a Cav2.1 voltage-gated Ca2+ channel mutant
Isabel Alonso1, Joana M Marques, Nuno Sousa
1UnIGENe, IBMC, Universidade do Porto, Portugal; ICBAS, Universidade do Porto, Portugal.
Abstract:
The leaner mutation in mice affects the Ca(v)2.1 voltage-gated calcium channel alpha(1A)-subunit gene (Cacna1a), causing a reduction in calcium currents predominantly in Purkinje cells. This reduction in calcium currents causes severe progressive cerebellar ataxia, beginning around postnatal day 10, in homozygous leaner mice (tg(la)/tg(la)), while their heterozygous littermates (tg(la)/+) present no obvious behavioral deficits. In humans, heterozygous mutations in the Cacna1a orthologous gene produce a broad range of neurological manifestations. To evaluate the phenotypic status of the tg(la)/+ animals, we assessed motor performance and cognition, at different ages, in these mutant mice. We were able to observe age-dependent impairment in motor and cognitive tasks; balance and motor learning deficits were found in demanding tasks on the rotarod and on the hanging wire test, while spatial learning and memory impairment was observed in the Morris water maze. Progressive dysfunction in escape reflexes, indicative of neurological impairment, was also present in tg(la)/+ animals. Although not presenting major motor alterations, tg(la)/+ mice show age-dependent motor and cognitive deficits.
Insights
Heterozygous Cacna1a mutations in mice cause age-dependent motor and cognitive deficits, impacting cerebellar function. These findings highlight subtle neurological impairments in carriers of the leaner mutation.
Area of Science:
- Neuroscience
- Genetics
- Physiology
Background:
- The leaner mutation in mice affects the Cacna1a gene, crucial for Ca(v)2.1 calcium channels.
- Homozygous leaner mice exhibit severe cerebellar ataxia due to reduced calcium currents in Purkinje cells.
- Human heterozygous CACNA1A mutations are linked to diverse neurological disorders.
Purpose of the Study:
- To investigate the subtle, age-dependent motor and cognitive deficits in heterozygous leaner mice (tg(la)/+).
- To evaluate the phenotypic consequences of Cacna1a gene variants in a mammalian model.
Main Methods:
- Assessment of motor performance using rotarod and hanging wire tests.
- Evaluation of spatial learning and memory via the Morris water maze.
- Monitoring of escape reflexes to detect neurological impairment progression.
Main Results:
- Heterozygous tg(la)/+ mice displayed age-dependent impairments in balance and motor learning.
- Spatial learning and memory deficits were evident in the Morris water maze.
- Progressive dysfunction in escape reflexes indicated underlying neurological changes.
Conclusions:
- Heterozygous Cacna1a mutations in mice lead to subtle, yet significant, age-dependent motor and cognitive deficits.
- These findings underscore the importance of Cacna1a in neurological function and suggest potential parallels with human CACNA1A-related disorders.
- The tg(la)/+ mouse model provides a valuable tool for studying the nuanced effects of calcium channel gene variants on brain function.
