Running increases neurogenesis in the dentate gyrus of the hippocampus, a brain structure that is important for memory function. Consequently, spatial learning and long-term potentiation (LTP) were tested in groups of mice housed either with a running wheel (runners) or under standard conditions (controls). Mice were injected with bromodeoxyuridine to label dividing cells and trained in the Morris water maze. LTP was studied in the dentate gyrus and area CA1 in hippocampal slices from these mice. Running improved water maze performance, increased bromodeoxyuridine-positive cell numbers, and selectively enhanced dentate gyrus LTP. Our results indicate that physical activity can regulate hippocampal neurogenesis, synaptic plasticity, and learning. N ew neurons are added continuously to certain areas of the adult brain, such as the hippocampus and olfactory bulb (1, 2). The functional significance of new hippocampal cells is not clear. In birds, food storage and retrieval experience correlate with changes in hippocampal size and neurogenesis (3). In mice, neurogenesis in the dentate gyrus increases with exposure to an enriched environment, and it is associated with improved learning (4). Similarly, voluntary physical activity in a running wheel enhances the number of new hippocampal cells (5). Although it is not known whether running also affects learning, it has been shown that physical activity facilitates recovery from injury (6) and improves cognitive function (7). Furthermore, trophic factors, associated with progenitor cell survival and differentiation (8), alterations in synaptic strength (9), long-term potentiation (LTP) (10), and memory function (11), are elevated after exercise (12, 13). At the cellular level, wheel running enhances the firing rate of hippocampal cells in a manner that correlates with running velocity (14). Thus, exercise may increase synaptic plasticity and learning, as well as neurogenesis. We designed the following experiments to test this hypothesis. Materials and MethodsSubjects. Thirty-four female C57BL͞6 mice, 3 months old (The Jackson Laboratory) were divided into two groups of 17, the controls and the runners. The runners had free access to a running wheel equipped with an electronic counter. During the first 10 days animals received one 10-mg͞ml intraperitoneal injection of 5-bromodeoxyuridine (BrdU; Sigma), dissolved in 0.9% NaCl, filtered sterile at 0.2 m, at 50 g͞g of body weight per day to label dividing cells.Spatial Learning. The mice were trained on a Morris water maze (15) with either two or four trials per day for 6 days. The platform was hidden 1 cm below the surface of water; it was made opaque with white nontoxic paint. The starting points were changed every day. Each trial lasted either until the mouse had found the platform or for a maximum of 40 s. At the end of each trial, the mice were allowed to rest on the platform for 10 s. The time to reach the platform (latency), the length of swim path, and the swim speed were recorded semi-automatically by a video trackin...

There is extensive evidence indicating that new neurons are generated in the dentate gyrus of the adult mammalian hippocampus, a region of the brain that is important for learning and memory. However, it is not known whether these new neurons become functional, as the methods used to study adult neurogenesis are limited to fixed tissue. We use here a retroviral vector expressing green fluorescent protein that only labels dividing cells, and that can be visualized in live hippocampal slices. We report that newly generated cells in the adult mouse hippocampus have neuronal morphology and can display passive membrane properties, action potentials and functional synaptic inputs similar to those found in mature dentate granule cells. Our findings demonstrate that newly generated cells mature into functional neurons in the adult mammalian brain.

A concerted effort to tackle the global health problem posed by traumatic brain injury (TBI) is long overdue. TBI is a public health challenge of vast, but insufficiently recognised, proportions. Worldwide, more than 50 million people have a TBI each year, and it is estimated that about half the world's population will have one or more TBIs over their lifetime. TBI is the leading cause of mortality in young adults and a major cause of death and disability across all ages in all countries, with a disproportionate burden of disability and death occurring in low-income and middle-income countries (LMICs). It has been estimated that TBI costs the global economy approximately $US400 billion annually. Deficiencies in prevention, care, and research urgently need to be addressed to reduce the huge burden and societal costs of TBI. This Commission highlights priorities and provides expert recommendations for all stakeholders—policy makers, funders, health-care professionals, researchers, and patient representatives—on clinical and research strategies to reduce this growing public health problem and improve the lives of people with TBI.Additional co-authors: Endre Czeiter, Marek Czosnyka, Ramon Diaz-Arrastia, Jens P Dreier, Ann-Christine Duhaime, Ari Ercole, Thomas A van Essen, Valery L Feigin, Guoyi Gao, Joseph Giacino, Laura E Gonzalez-Lara, Russell L Gruen, Deepak Gupta, Jed A Hartings, Sean Hill, Ji-yao Jiang, Naomi Ketharanathan, Erwin J O Kompanje, Linda Lanyon, Steven Laureys, Fiona Lecky, Harvey Levin, Hester F Lingsma, Marc Maegele, Marek Majdan, Geoffrey Manley, Jill Marsteller, Luciana Mascia, Charles McFadyen, Stefania Mondello, Virginia Newcombe, Aarno Palotie, Paul M Parizel, Wilco Peul, James Piercy, Suzanne Polinder, Louis Puybasset, Todd E Rasmussen, Rolf Rossaint, Peter Smielewski, Jeannette Söderberg, Simon J Stanworth, Murray B Stein, Nicole von Steinbüchel, William Stewart, Ewout W Steyerberg, Nino Stocchetti, Anneliese Synnot, Braden Te Ao, Olli Tenovuo, Alice Theadom, Dick Tibboel, Walter Videtta, Kevin K W Wang, W Huw Williams, Kristine Yaffe for the InTBIR Participants and Investigator