Involvement of Adult-born and Preexisting Olfactory Bulb and Dentate Gyrus Neurons in Single-trial Olfactory Memory Acquisition and Retrieval.

The production of new neurons and their incorporation into preexisting neuronal circuits occur throughout adulthood in the olfactory bulb and the hippocampal dentate gyrus of the mammalian brain. To determine whether the adult-born neurons are engaged in the acquisition and retrieval of olfactory associative memory, we developed and validated a single-trial olfactory fear conditioning protocol in mice which allows to detect activation of newborn neurons during a specific episode of memory acquisition. Using c-Fos mapping of neuronal activity, we then examined the activation of new and preexisting neurons during training and testing sessions. We found that a single trial of olfactory fear conditioning did not lead to a significant increase in the number of c-Fos-positive granule cells (GCs) of the olfactory bulb and the dentate gyrus. However, the activity of these two cell populations was dramatically increased during memory retrieval. Activation of neurons in the dentate gyrus during memory retrieval was observed mainly in the suprapyramidal blade. In the olfactory bulb, 1.6-2.7% of newborn GCs marked with thymidine analogues (2, 4, and 6 weeks old) expressed c-Fos during memory retrieval, while in the dentate gyrus no newborn neurons were found among the c-Fos-positive cells. These data are consistent with the hypothesis that adult-born GCs of the olfactory bulb are less involved in odor-cued associative fear memory than in odor-cued operant behavior memory.

Kedrov AV ，Mineyeva OA ，Enikolopov GN ，Anokhin KV ... -  《-》

A critical time window for the recruitment of bulbar newborn neurons by olfactory discrimination learning.

Belnoue L ，Grosjean N ，Abrous DN ，Koehl M ... -  《-》

Continuous postnatal neurogenesis contributes to formation of the olfactory bulb neural circuits and flexible olfactory associative learning.

Sakamoto M ，Ieki N ，Miyoshi G ，Mochimaru D ，Miyachi H ，Imura T ，Yamaguchi M ，Fishell G ，Mori K ，Kageyama R ，Imayoshi I ... -  《-》

A combination of running and memantine increases neurogenesis and reduces activation of developmentally-born dentate granule neurons in rats.

During hippocampal-dependent memory formation, sensory signals from the neocortex converge in the dentate gyrus. It is generally believed that the dentate gyrus decorrelates inputs in order to minimize interference between codes for similar experiences, often referred to as pattern separation. The proportion of dentate neurons that are activated by experience is therefore likely to impact how memories are stored and separated. Emerging evidence from mouse models suggests that adult-born neurons can both increase and decrease activity levels in the dentate gyrus. However, the conditions that determine the direction of this modulation, and whether it occurs in other species, remains unclear. Furthermore, since the dentate gyrus is composed of a heterogeneous population of cells that are born throughout life, newborn neurons may not modulate all cells equally. We aimed to investigate whether adult neurogenesis in rats regulates activity in dentate gyrus neurons that are born at the peak of early postnatal development. Adult neurogenesis was increased by subjecting rats to an alternating running and memantine treatment schedule, and it was decreased with a transgenic GFAP-TK rat model. Activity was measured by Fos expression in BrdU+ cells after rats explored a novel environment. Running+memantine treatment increased adult neurogenesis by only 17%, but completely blocked experience-dependent Fos expression. In contrast, GFAP-TK rats had a 68% reduction in adult neurogenesis but normal experience-dependent Fos expression. The inconsistent relationship between neurogenesis and Fos expression suggests that neurogenesis does not regulate DG activity during exploration of a novel environment. Nonetheless, running and memantine may benefit disorders where there is elevated activity in the dentate gyrus, such as anxiety and age-related memory impairments.

Cahill SP ，Martinovic A ，Cole JD ，Seib DR ，Snyder JS ... -  《-》

Impaired fear memory and decreased hippocampal neurogenesis following olfactory bulbectomy in rats.

Jaako-Movits K ，Zharkovsky A 《-》