A lifetime of neurogenesis in the olfactory system

Brann, Jessica H.; Firestein, Stuart

doi:10.3389/fnins.2014.00182

Cited by 185 publications

(163 citation statements)

References 153 publications

(198 reference statements)

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“…Compartmentalization as a basic feature of the transduction machinery in rods could also be a characteristic of other sensory neurons, such as cones (38,43) and olfactory sensory neurons (44)(45)(46)(47) and could explain the high turnover and renewal of these cells. Not only sensory neurons, which have an intrinsic functional specialization, are likely to be compartmentalized but possibly the great majority of cells have a similar internal organization.…”

Section: Discussionmentioning

confidence: 99%

The phototransduction machinery in the rod outer segment has a strong efficacy gradient

Mazzolini

Facchetti

Andolfi

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Rod photoreceptors consist of an outer segment (OS) and an inner segment. Inside the OS a biochemical machinery transforms the rhodopsin photoisomerization into electrical signal. This machinery has been treated as and is thought to be homogenous with marginal inhomogeneities. To verify this assumption, we developed a methodology based on special tapered optical fibers (TOFs) to deliver highly localized light stimulations. By using these TOFs, specific regions of the rod OS could be stimulated with spots of light highly confined in space. As the TOF is moved from the OS base toward its tip, the amplitude of saturating and single photon responses decreases, demonstrating that the efficacy of the transduction machinery is not uniform and is 5-10 times higher at the base than at the tip. This gradient of efficacy of the transduction machinery is attributed to a progressive depletion of the phosphodiesterase along the rod OS. Moreover we demonstrate that, using restricted spots of light, the duration of the photoresponse along the OS does not increase linearly with the light intensity as with diffuse light.V ertebrate photoreceptors, rods and cones, are morphologically specialized light sensing neurons and consist of four parts: an outer segment (OS), an inner segment (IS), the nuclear region, and the synapse (1). The OS of rod photoreceptors is stacked with thousands of lipid discs containing rhodopsin molecules that absorb photons (2-4). They are surrounded by a plasma membrane and differ in their lipid and protein composition.It is known that within 1 s, each excited rhodopsin, densely packed in the disc membrane, activates tens of G proteins (named transducin), each of which activates one phosphodiesterase (PDE) molecule (5-7). Activated PDEs rapidly hydrolyze cytoplasmic cyclic guanosine monophosphate (cGMP) thereby closing cyclic nucleotide-gated (CNG) channels (8, 9). In darkness, a current carried by Na + , K + , and Ca 2+ ions, which is known as the photocurrent, enters via the CNG channels into the OS and is pumped out by Na + /K + ATPase, located in the IS (1). This current can be recorded using suction electrodes (3, 10).The existence of distinct compartments on photoreceptor OSs is a consequence of their function. The OS is a highly modified nonmotile cilium developed for the absorption of light that is translated into the electrical signal. The IS and the nuclear region-containing the organelles and the nucleus-are dedicated to metabolism, homeostasis, and synthesis of the membrane and transportation of proteins and lipids supplied to the OS by an extensive trafficking through the tight restriction connecting the OS to the IS (11). Considering that, unlike typical cilia, the OS is continuously renewed throughout its entire life and given the varying density and asymmetry of the molecules involved, it is not surprising to find an efficacy gradient of phototransduction between the base and the tip. Indeed, the cholesterol (12, 13), the phospholipids (13-15), the CNG channels, the PDE (16), and the rhodop...

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Section: Discussionmentioning

confidence: 99%

The phototransduction machinery in the rod outer segment has a strong efficacy gradient

Mazzolini

Facchetti

Andolfi

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Information on age effects on neurogenesis in the olfactory system has not received as much attention as for the hippocampus (but see the review in Brann and Firestein 2014). Although, in 1997, Tropepe, van der Kooy, and colleagues reported that the aging subventricular zone (SVZ) contained fewer precursor cells than in younger rats (Tropepe et al 1997), only in 2004 was a direct in vivo study published (Enwere et al 2004).…”

Section: Age Effects On Adult Neurogenesismentioning

confidence: 99%

Activity Dependency and Aging in the Regulation of Adult Neurogenesis

Kempermann

2015

Cold Spring Harb Perspect Biol

100

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Age and activity might be considered the two antagonistic key regulators of adult neurogenesis. Adult neurogenesis decreases with age but remains present, albeit at a very low level, even in the oldest individuals. Activity, be it physical or cognitive, increases adult neurogenesis and thereby seems to counteract age effects. It is, thus, proposed that activity-dependent regulation of adult neurogenesis might contribute to some sort of "neural reserve," the brain's ability to compensate functional loss associated with aging or neurodegeneration. Activity can have nonspecific and specific effects on adult neurogenesis. Mechanistically, nonspecific stimuli that largely affect precursor cell stages might be related by the local microenvironment, whereas more specific, survival-promoting effects take place at later stages of neuronal development and require the synaptic integration of the new cell and its particular synaptic plasticity.

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“…The OSNs are true neurons (Golgi type I) that have the unique property of being continuously renewed by neurogenesis, a process involving the cycle of birth, maturation, and death (7). As a consequence of continuous neurogenesis, the olfactory epithelium contains OSNs at different stages of maturation, while the number of live OSNs at any given time is a result of the balance between the rates of their generation and death (7).…”

Section: In Vivo Imaging With Petmentioning

confidence: 99%