Regeneration of Hippocampal Neurons

The hippocampus is an area of the brain that is crucial for cognitive activities, learning, and memory. Proliferating NSCs with long-term renewal potential have been identified in the hippocampus of mice and rats (Rao, 1999; Gage, 2000; Momma et al., 2000; Guena et al., 2001; Rietze et al., 2001), marmoset monkeys (Gould et al., 1998), and deceased human patients given BrdU as part of a cancer study (Eriksson et al., 1998).

The precise location of hippocampal NSCs is still unclear. The dentate gyrus, located within the hippocampus itself, is one possibility. Human dentate gyrus cells purified by FACS and transfected with the GFP gene under the control of the nestin enhancer or the Ta1 tubulin promoter proliferated in vitro and differentiated morphologically, antigenically, and electro-physiologically as neurons (Roy et al., 2000). However, these cells have limited self-renewal capacity, suggesting that they are a transit-amplifying population of progenitors, whereas the lateral ventricular wall adjacent to the hippocampus has been shown to contain multipotent NSCs with long-term self-renewal capacity (Seaberg and Van der Kooy, 2002).

Regardless of their location, the presence of NSCs in the hippocampus suggests that maintenance regeneration might be crucial for the retention or formation of memory and for learning new information and tasks. Several experimental results support this idea. Studies in vivo strongly suggest that the number of new neurons born in the hippocampus of mice is influenced by both physical and cognitive activity. Running on a treadmill, or placement in an enriched environment (more mice per cage to increase social interactions, mouse toys and treats, and re-arrangable sets of tunnels) increased stem cell proliferation and neurogenesis in the dentate gyrus of mice above the level of controls (Kempermann et al., 1998; van Praag et al., 1999a, b). Enriched-environment mice also learned a maze faster than controls. Control mice exhibited a decline in the number of BrdU-labeled new neurons in the hippocampus with age that was correlated with a reduction in the speed at which the maze was learned. The reduction in number of BrdU-labeled differentiated neurons in aged animals was reduced by more than half when they were placed in an enriched environment (Kempermann et al., 1998).

(A) Conditioning regimen

Sound Delay neutral ->-

tone

Give noxious eyelid stimulus

Eyelid response (Blinking)

(B) Conditioned response

Sound neutral tone

Eyelid response (Blinking)

(C) Inhibit neurogenesis in conditioned rats with MAM

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Responses

  • gilly
    Is hippocampus is regenerative 2017?
    2 years ago

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