Table 2.

Behavioral test results in C3 KO and WT mice at 4 mo and 16 mo of age

Behavior tests	4 mo	16 mo
	C3 KO vs WT	C3 KO vs WT
No change
Baseline behavior
SHIRPA	Normal	Normal
Rotarod	Normal	Normal
Grip strength	Normal	Normal
Social interaction	Normal	Normal
Age-dependent
Cognition/memory
Water maze	Morris water maze	WTM
	Normal	Better memory
CFC	Froze more (d 1); better learning	Froze more (d 1 and 2)
		Better learning and memory
Anxiety
OF	Normal	Increased time in center
		Less anxiety
EPM	Normal	Increased open arm entries
		Less anxiety
OH	Normal	More contacts in min 1
		Fewer contacts in min 3

For motor and social behavior, we performed SHIRPA, Rotarod, grip strength and social interaction tests, none of which revealed any differences between genotypes at either 4 or 16 months of age. In terms of cognition/memory, 4-month-old C3 KO mice froze longer during CFC training compared with WT mice, suggesting better learning in the C3 KO mice compared with 4-month-old WT mice. No differences were found in the CFC memory test and WTM between 4-month-old C3 KO and WT mice. However, 16-month-old C3 KO mice performed better than 16-month-old WT mice in the reversal phase of the WTM test (i.e. enhanced cognitive flexibility) and spent more time freezing in both the training and testing sessions of the CFC test, suggesting that C3 deficiency rescued age-dependent learning and memory deficits. In addition, 16-month-old C3 KO mice demonstrated anxiolytic-like behavior compared with age-matched WT mice in three different tests. The aged C3 KO mice spent significantly more time in the center of the arena in the OF test, showed more total open arm entries in the EPM test, and made significantly more contacts with the novel object during the first minute and fewer contacts during the third minute in the OH test compared with aged WT mice.