Zhang CL, Zou Y, He W, Gage FH, Evans RM.
A role for adult TLX-positive neural stem cells in learning and behaviour.
Nature. 2008 Feb 21;451(7181):1004-7.
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This is a very elegant study supporting a role for neurogenesis in water maze performance. This study re-emphasizes that the design of the water maze test might modulate the ability to detect this role. For example, in this study the effects of reduced neurogenesis on water maze performance were not detected when the mice were first trained to locate a visible target (task learning). However, it might be more complex, and what might also be very important is whether there is only one probe trial (no target) at the end of the hidden water maze training or whether there are multiple probe trials during hidden water maze training. In addition, there might be a species difference. Training the animals first to locate a visible platform and using one probe trial only at the end of the hidden water maze training, we did not see impairments in water maze performance in 2-month-old C57Bl6/J wild-type mice X-irradiated at 10 Gy and tested 3 months later (Raber et al., 2004), although using a similar water maze paradigm (visible platform training; hidden platform training; probe trial), we did see impairments in water maze performance in gerbils: irradiated gerbils spent less time in the target quadrant in the probe trial than vehicle controls (Raber et al., 2004). This does not mean that there were no detrimental effects of cranial irradiation on spatial learning and memory in the mouse study, as such effects were detected in the Barnes maze test.
Importantly, training mice first to locate a visible platform followed by training mice to locate a hidden platform and performing a probe trial at the end of each day of hidden platform training, we did see impairments in spatial memory retention in the probe trial in C57Bl6/J wild-type mice irradiated at 5 Gy at 3 weeks of age and behaviorally tested 3 months later (Rola et al., 2004) and in human ApoE transgenic female mice irradiated at 10 Gy at 2 months of age and behaviorally tested 3 months later (Villasana et al., 2006). Thus, the impairments in water maze performance might be overcome with extended training. Although not first training the mice to locate a visible platform or including additional probe trials during hidden water maze training might both make the water maze test more challenging and allow effects of reduced neurogenesis on water maze performance to be detected, there is an important difference. Training to locate a visible platform is not hippocampus-dependent and does not require hippocampal neurogenesis. In addition, without first training the mice to locate a visible platform, it is hard to distinguish potential differences in task learning (training the animals that they need to swim to the target) from differences in spatial learning and memory. Clearly, more work is needed to fully understand the exact role of neurogenesis in spatial learning and memory.
Raber J, Rola R, LeFevour A, Morhardt D, Curley J, Mizumatsu S, Vandenberg SR, Fike JR.
Radiation-induced cognitive impairments are associated with changes in indicators of hippocampal neurogenesis.
Radiat Res. 2004 Jul;162(1):39-47.
Raber J, Fan Y, Matsumori Y, Liu Z, Weinstein PR, Fike JR, Liu J.
Irradiation attenuates neurogenesis and exacerbates ischemia-induced deficits.
Ann Neurol. 2004 Mar;55(3):381-9.
Rola R, Raber J, Rizk A, Otsuka S, VandenBerg SR, Morhardt DR, Fike JR.
Radiation-induced impairment of hippocampal neurogenesis is associated with cognitive deficits in young mice.
Exp Neurol. 2004 Aug;188(2):316-30.
Villasana L, Acevedo S, Poage C, Raber J.
Sex- and APOE isoform-dependent effects of radiation on cognitive function.
Radiat Res. 2006 Dec;166(6):883-91.