Calcium Buffering by Mitochondria Prolongs Synaptic Responses
Yuliya V. Medvedeva, Man-Su Kim, and Yuriy M. Usachev
(see pages 5295–5311)
Mitochondria can transform brief stimulation into long-lasting responses by rapidly sequestering and slowly releasing calcium, according to Medvedeva et al. Activation of presynaptic TRPV1 channels in cultures of dorsal root ganglion and spinal neurons induced a biphasic calcium response in the axonal boutons: upon capsaicin application, cytoplasmic calcium concentration rapidly increased; then, after washout, the calcium concentration decreased to a plateau level that lasted for ∼15 min before returning to baseline. These changes were paralleled by increased glutamate release, which increased EPSC frequency in postsynaptic neurons for the duration of the calcium plateau. Although calcium influx through TRPV1 channels produced the initial calcium increase, release from mitochondria was responsible for the plateau phase. Furthermore, blocking calcium uptake by mitochondria not only eliminated the plateau but also increased the amplitude of the initial calcium response, suggesting that mitochondria both limit the amplitude and prolong the duration of the response.
Depolarization Unmasks Latent Hippocampal Stem Cells
Tara L. Walker, Amanda White, Debra M. Black, Robyn H. Wallace, Pankaj Sah, and Perry F. Bartlett
(see pages 5240–5247)
Although neurons are generated in the hippocampus throughout life, researchers have been unable to isolate the stem cells capable of generating new neurons from adult hippocampus. To assay for stem cells, dissociated neurons are grown in suspension culture, which causes stem cells and progenitors to form neurospheres. Walker et al. reasoned that because neuronal activity increases adult neurogenesis, such activity might activate otherwise latent stem cells. Indeed, depolarizing cultured mouse hippocampal neurons with KCl increased the number of neurospheres formed. Some of the largest of these (about eight per hippocampus) contained multipotent stem cells that could be passaged several times and produced neurons upon differentiation. In contrast, KCl did not increase the number of neurospheres formed from neonatal hippocampus (which formed many neurospheres in the absence of activity), and although depolarization increased the number of neurospheres produced from aged hippocampus, these were only small neurospheres that did not contain stem cells.
Auditory Motion Activates Area MT in Blind Subjects
Melissa Saenz, Lindsay B. Lewis, Alexander G. Huth, Ione Fine, and Christof Koch
(see pages 5141–5148)
It is well known that visual cortical areas become responsive to other sensory modalities in people who become blind at an early age. But because the precise boundaries of most visual areas must be defined functionally (i.e., by their activation in visual tasks), it has been impossible to determine whether these areas retain their original function. To overcome this problem, Saenz et al. have studied the function of visual cortical area MT+ in two subjects who were blinded at a young age but had their vision restored decades later. MT+ in formerly blind subjects responded normally to visual motion. In addition, however, MT+ responded to apparent auditory motion, even though vision had been restored for years. Interestingly, MT+ was not activated by other auditory stimuli (stationary volume changes, frequency sweeps, or speech), suggesting MT+ functions in motion detection regardless of what mode of sensory input it receives.
Neurobiology of Disease
APOE Genotype Alters Amyloid Plaque Deposition
Feng Xu, Michael P. Vitek, Carol A. Colton, Mary Lou Previti, Nastaran Gharkholonarehe, Judianne Davis, and William E. Van Nostrand
(see pages 5312–5320)
Mutations in amyloid precursor protein (APP) and apolipoprotein E (APOE) are linked to an increased risk of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). To study how these proteins interact, Xu et al. created transgenic mice with mutant APP in addition to either of two APOE mutations: ApoE4 (an APOE allele that increases AD risk) or ApoE3 (a more common allele). Mice with mutant APP but normal APOE had a CAA-like pattern of amyloid deposits: many fibrillar amyloid plaques surrounded the cerebral microvasculature and diffuse (nonfibrillar) deposits formed in the parenchyma. In contrast, APP-mutant mice with either ApoE mutation had significantly fewer plaques in the microvasculature and many more plaques in the parenchyma. Despite this shift, the total amount of soluble and insoluble Aβ was unchanged. The distribution of reactive astrocytes and microglia paralleled that of fibrillar amyloid plaques, indicating that inflammation in AD and CAA is linked to amyloid deposition.