The effect of load placement on the power production characteristics of three lower extremity jumping exercises

The purpose of this study was to compare the power production characteristics of the jump squat (JS), hexagonal barbell jump (HEXJ), and jump shrug (JShrug) across a spectrum of relative loads. Fifteen resistance-trained men completed three testing sessions where they performed repetitions of either the JS, HEXJ, or JShrug at body mass (BM) or with 20, 40, 60, 80, or 100% of their BM. Relative peak power (PPRel), relative force at PP (FPP), and velocity at PP (VPP) were compared between exercises and loads. In addition, power-time curves at each load were compared between exercises. Load-averaged HEXJ and JShrug PPRel were statistically greater than the JS (both p < 0.01), while no difference existed between the HEXJ and the JShrug (p = 1.000). Load-averaged JShrug FPP was statistically greater than both the JS and the HEXJ (both p < 0.001), while no statistical difference existed between the JS and the HEXJ (p = 0.111). Load averaged JS and HEXJ VPP were statistically greater than the JShrug (both p < 0.01). In addition, HEXJ VPP was statistically greater than the JS (p = 0.009). PPRel was maximized at 40, 40, and 20% BM for the JS, HEXJ, and JShrug, respectively. The JShrug possessed statistically different power-time characteristics compared to both the JS and the HEXJ during the countermovement and propulsion phases. The HEXJ and the JShrug appear to be superior exercises for PPRel compared to the JS. The HEXJ may be considered a more velocity-dominant exercise, while the JShrug may be a more force-dominant one

Mouse Embryonic Retina Delivers Information Controlling Cortical Neurogenesis

The relative contribution of extrinsic and intrinsic mechanisms to cortical development is an intensely debated issue and an outstanding question in neurobiology. Currently, the emerging view is that interplay between intrinsic genetic mechanisms and extrinsic information shape different stages of cortical development [1]. Yet, whereas the intrinsic program of early neocortical developmental events has been at least in part decoded [2], the exact nature and impact of extrinsic signaling are still elusive and controversial. We found that in the mouse developing visual system, acute pharmacological inhibition of spontaneous retinal activity (retinal waves-RWs) during embryonic stages increase the rate of corticogenesis (cell cycle withdrawal). Furthermore, early perturbation of retinal spontaneous activity leads to changes of cortical layer structure at a later time point. These data suggest that mouse embryonic retina delivers long-distance information capable of modulating cell genesis in the developing visual cortex and that spontaneous activity is the candidate long-distance acting extrinsic cue mediating this process. In addition, these data may support spontaneous activity to be a general signal coordinating neurogenesis in other developing sensory pathways or areas of the central nervous system

GABA Maintains the Proliferation of Progenitors in the Developing Chick Ciliary Marginal Zone and Non-Pigmented Ciliary Epithelium

GABA is more than the main inhibitory neurotransmitter found in the adult CNS. Several studies have shown that GABA regulates the proliferation of progenitor and stem cells. This work examined the effects of the GABAA receptor system on the proliferation of retinal progenitors and non-pigmented ciliary epithelial (NPE) cells. qRT-PCR and whole-cell patch-clamp electrophysiology were used to characterize the GABAA receptor system. To quantify the effects on proliferation by GABAA receptor agonists and antagonists, incorporation of thymidine analogues was used. The results showed that the NPE cells express functional extrasynaptic GABAA receptors with tonic properties and that low concentration of GABA is required for a baseline level of proliferation. Antagonists of the GABAA receptors decreased the proliferation of dissociated E12 NPE cells. Bicuculline also had effects on progenitor cell proliferation in intact E8 and E12 developing retina. The NPE cells had low levels of the Cl–transporter KCC2 compared to the mature retina, suggesting a depolarising role for the GABAA receptors. Treatment with KCl, which is known to depolarise membranes, prevented some of the decreased proliferation caused by inhibition of the GABAA receptors. This supported the depolarising role for the GABAA receptors. Inhibition of L-type voltage-gated Ca2+ channels (VGCCs) reduced the proliferation in the same way as inhibition of the GABAA receptors. Inhibition of the channels increased the expression of the cyclin-dependent kinase inhibitor p27KIP1, along with the reduced proliferation. These results are consistent with that when the membrane potential indirectly regulates cell proliferation with hyperpolarisation of the membrane potential resulting in decreased cell division. The increased expression of p27KIP1 after inhibition of either the GABAA receptors or the L-type VGCCs suggests a link between the GABAA receptors, membrane potential, and intracellular Ca2+ in regulating the cell cycle

GABAergic regulation of cerebellar NG2 cell development is altered in perinatal white matter injury.

Diffuse white matter injury (DWMI), a leading cause of neurodevelopmental disabilities in preterm infants, is characterized by reduced oligodendrocyte formation. NG2-expressing oligodendrocyte precursor cells (NG2 cells) are exposed to various extrinsic regulatory signals, including the neurotransmitter GABA. We investigated GABAergic signaling to cerebellar white matter NG2 cells in a mouse model of DWMI (chronic neonatal hypoxia). We found that hypoxia caused a loss of GABAA receptor-mediated synaptic input to NG2 cells, extensive proliferation of these cells and delayed oligodendrocyte maturation, leading to dysmyelination. Treatment of control mice with a GABAA receptor antagonist or deletion of the chloride-accumulating transporter NKCC1 mimicked the effects of hypoxia. Conversely, blockade of GABA catabolism or GABA uptake reduced NG2 cell numbers and increased the formation of mature oligodendrocytes both in control and hypoxic mice. Our results indicate that GABAergic signaling regulates NG2 cell differentiation and proliferation in vivo, and suggest that its perturbation is a key factor in DWMI

Interactive histogenesis of axonal strata and proliferative zones in the human fetal cerebral wall

Development of the cerebral wall is characterized by partially overlapping histogenetic events. However, little is known with regards to when, where, and how growing axonal pathways interact with progenitor cell lineages in the proliferative zones of the human fetal cerebrum. We analyzed the developmental continuity and spatial distribution of the axonal sagittal strata (SS) and their relationship with proliferative zones in a series of human brains (8-40 post-conceptional weeks; PCW) by comparing histological, histochemical, and immunocytochemical data with magnetic resonance imaging (MRI). Between 8.5 and 11 PCW, thalamocortical fibers from the intermediate zone (IZ) were initially dispersed throughout the subventricular zone (SVZ), while sizeable axonal "invasion" occurred between 12.5 and 15 PCW followed by callosal fibers which "delaminated" the ventricular zone-inner SVZ from the outer SVZ (OSVZ). During midgestation, the SS extensively invaded the OSVZ, separating cell bands, and a new multilaminar axonal-cellular compartment (MACC) was formed. Preterm period reveals increased complexity of the MACC in terms of glial architecture and the thinning of proliferative bands. The addition of associative fibers and the formation of the centrum semiovale separated the SS from the subplate. In vivo MRI of the occipital SS indicates a "triplet" structure of alternating hypointense and hyperintense bands. Our results highlighted the developmental continuity of sagittally oriented "corridors" of projection, commissural and associative fibers, and histogenetic interaction with progenitors, neurons, and glia. Histogenetical changes in the MACC, and consequently, delineation of the SS on MRI, may serve as a relevant indicator of white matter microstructural integrity in the developing brain

Functional aspects of neurogenesis in the adult olfactory bulb

New cells expressing neuronal markers are generated postnatally at the subventricular zone of the forebrain, and from there they migrate into the olfactory bulb (OB) following a well defined pathway, the rostral migratory stream (RMS). However, it is still unclear whether newly generated cells (NGC) that express neuronal markers become functional neurones. To fill this gap we combined a retroviral mediated cell lineage and patch-clamp electrophysiology. We have identified one-month old neurones with functional properties similar to those of mature periglomerular (PG) and granule cells in the adult OB. From these cells we recorded action potentials in response to the injection of depolarising currents, and we have isolated and characterised Na+ and K+ currents. About 50% of the NGC were PG cells; the remaining ended their migration between internal plexiform and mitral cell layers, or in the granule cell layer. The migrating neuroblasts within the RMS show only a small delayed rectifier K-current, to which an A-current is added when the OB is reached. The mature cells lose the delayed rectifier K+-current, and only display A- and Na+ currents. Finally, by recordings action potentials and excitatory synaptic currents in response to stimulation of the olfactory nerve. These results show that endogenous neuronal progenitors produce new neurons that integrate into previously established and functioning circuits. Supported by grants from Fondazione Caricento (O.B.) and NIH (MH56524, J.J.L.)

Electrophysiological Differentiation of New Neurons in the Olfactory Bulb

The subventricular zone produces neuroblasts that migrate to the olfactory bulb (OB) and differentiate into interneurons throughout postnatal life (Altman and Das, 1966; Hinds, 1968; Altman, 1969; Kishi et al., 1990; Luskin, 1993; Lois and Alvarez-Buylla, 1994). Although such postnatally generated interneurons have been characterized morphologically, their physiological differentiation has not been thoroughly described. Combining retroviral-mediated labeling of newly generated neurons with patch-clamp electrophysiology, we demonstrated that soon after new cells enter the layers of the olfactory bulb, they display voltage-dependent currents typical of more mature neurons. We also show that these "newcomers" express functional GABA and glutamate receptor channels, respond synaptically to stimulation of the olfactory nerve, and may establish both axodendritic and dendrodendritic synaptic contacts within the olfactory bulb. These data provide a basic description of the physiology of newly generated cells in the OB and show that such new cells are functional neurons that synaptically integrate into olfactory bulb circuitry soon after their arrival