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Published on: June 13, 2015
Learning defects in Drosophila growth restricted chico mutants are caused by attenuated adenylyl cyclase activity
Shintaro Naganos1, Kohei Ueno1, Junjiro Horiuchi1
1Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya, 185-8506, Tokyo, Japan.
Insights
Mutations in the chico gene disrupt olfactory learning in Drosophila by reducing cAMP signaling in mushroom bodies. This impairment in learning occurs independently of growth defects, suggesting a direct link between cAMP levels and cognitive function.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Reduced insulin/insulin-like growth factor signaling (IIS) causes intrauterine growth retardation (IUGR), leading to global growth defects and mental retardation.
- The Drosophila gene chico encodes the sole insulin receptor substrate, and its mutants exhibit growth and learning deficits.
- The precise mechanisms underlying learning impairments in chico mutants and IUGR remain unclear.
Purpose of the Study:
- To investigate the physiological and molecular basis of learning defects in Drosophila chico mutants.
- To determine if chico mutations affect memory-associated synaptic plasticity in the mushroom bodies (MBs).
- To elucidate the role of cAMP signaling in the learning deficits associated with reduced IIS.
Main Methods:
- Examined memory-associated synaptic plasticity in the mushroom bodies (MBs) of chico mutants.
- Assessed the expression of rutabaga-type adenylyl cyclase (rut) and cAMP synthesis in MBs.
- Utilized a rut (+) transgene to rescue plasticity and learning in chico mutants.
Main Results:
- Chico mutations impair memory-associated synaptic plasticity in Drosophila MBs.
- Mutations in chico lead to reduced rut expression and decreased cAMP synthesis in MBs.
- Restoring rut expression in MBs rescues plasticity and olfactory learning in chico mutants without affecting growth.
Conclusions:
- Chico mutations disrupt olfactory learning, at least in part, by reducing cAMP signaling in MBs.
- Cognitive defects associated with reduced IIS may arise from acute reductions in cAMP signaling, independent of developmental defects.
Background:
Reduced insulin/insulin-like growth factor signaling (IIS) is a major cause of symmetrical intrauterine growth retardation (IUGR), an impairment in cell proliferation during prenatal development that results in global growth defects and mental retardation. In Drosophila, chico encodes the only insulin receptor substrate. Similar to other animal models of IUGR, chico mutants have defects in global growth and associative learning. However, the physiological and molecular bases of learning defects caused by chico mutations, and by symmetrical IUGR, are not clear.
Results:
In this study, we found that chico mutations impair memory-associated synaptic plasticity in the mushroom bodies (MBs), neural centers for olfactory learning. Mutations in chico reduce expression of the rutabaga-type adenylyl cyclase (rut), leading to decreased cAMP synthesis in the MBs. Expressing a rut (+) transgene in the MBs restores memory-associated plasticity and olfactory associative learning in chico mutants, without affecting growth. Thus chico mutations disrupt olfactory learning, at least in part, by reducing cAMP signaling in the MBs.
Conclusions:
Our results suggest that some cognitive defects associated with reduced IIS may occur, independently of developmental defects, from acute reductions in cAMP signaling.
