Enhanced proliferation of progenitor cells following long-term potentiation induction in the rat dentate gyrus

The dentate gyrus (DG) is among the few areas in the mammalian brain where production of new neurons continues in the adulthood. Although its functional significance is not completely understood, several lines of evidence suggest the role of DG neurogenesis in learning and memory. Considering that long-term potentiation (LTP) is a prime candidate for the process underlying hippocampal learning and memory, these results raise the possibility that LTP and neurogenesis are closely related. Here, we investigated whether or not LTP induction in the afferent pathway triggers enhanced proliferation of progenitor cells in the DG. LTP was induced by tetanic stimulation in perforant path-DG synapses in one hemisphere, and the number of newly generated progenitor (BrdU-labeled) cells in the DG was quantified. Compared with the control hemisphere (stimulated with low-frequency pulses), the LTP-induced hemisphere contained a significantly higher number of newly generated progenitor cells in the dorsal as well as ventral DG. When CPP, an NMDA receptor antagonist, was administered, tetanic stimulation neither induced LTP nor enhanced progenitor cell proliferation, indicating that NMDA receptor activation, rather than tetanic stimulation per se, is responsible for enhanced progenitor proliferation in the control animal. Our results show that tetanic stimulation of perforant path sufficient to induce LTP increases progenitor proliferation in adult DG in an NMDA receptor-dependent manner.     

A putative role for neurogenesis in neurocomputational terms: Inferences from a hippocampal model

New neurons are generated daily in the hippocampus during adult life. They are integrated into the existing neuronal circuits according to several factors such as age, physical exercise and hormonal status. At present, the role of these new neurons is debated. Computational simulations of hippocampal function allow the effects of neurogenesis to be explored, at least from a computational perspective. The present work implements a model of neurogenesis in the hippocampus with artificial neural networks, based on a standard theoretical model of biologically plausible hippocampal circuits. The performance of the model in retrieval of a variable number of patterns or memories was evaluated (episodic memory evaluation). The model increased, in a phase subsequent to initial learning, the number of granular cells by 30% relative to their initial number. In contrast to a model without neurogenesis, the retrieval of recent memories was very significantly improved, although remotes memories were only slightly affected by neurogenesis. This increase in the quality of retrieval of new memories represents a clear advantage that we attribute to the neurogenesis process. This advantage becomes more significant for higher storage loads. The model presented here suggests an important functional role of neurogenesis on learning and memory.     

Hippocampus-dependent strategy choice predicts low levels of cell proliferation in the dentate gyrus

Neurogenesis continues to occur throughout life in the mammalian hippocampus. Previous research has suggested that the production of new neurons in the hippocampus during adulthood may be related to hippocampus-dependent learning and memory. However, the exact relationship between adult neurogenesis and learning and memory remains unclear. Here we investigated whether learning strategy selection is related to cell proliferation or to survival of new neurons in the hippocampus of adult male rats. We trained rats on alternating blocks of hippocampus-dependent (hidden platform) and hippocampus-independent (visible platform) versions of the Morris water task with the platform always in the same position. Following training, rats were given a probe session during which the platform was visible and in a novel location. Preferred strategy was determined by observing the initial swim path. Rats were classified as place strategy (hippocampus-dependent) users if they swam to the old platform location. Cue strategy (hippocampus-independent) users were classified as those rats that swam initially to the visible platform. Our results indicate that rats that preferentially used a place strategy had significantly lower cell proliferation than cue strategy users. However, there was no significant difference in cell survival or number of immature neurons between strategy user groups. These results suggest that low levels of cell proliferation in the dentate gyrus may be conducive or coincident with more efficient memory processing in the hippocampus.     

神经科学领域百年教条被打破引发的思考和启示

有关成年脑组织神经元再生的研究是当前神经科学研究的热点内容。相关的研究使得成年脑神经元不能再生“百年教条”不断受到挑战并最终被打破,这一历程体现了科学理论发展的一般规律和特点,给我们带来许多有益的思考和启示。