L-Type Calcium Channels Govern Calcium Signaling in Migrating Newborn Neurons in the Postnatal Olfactory Bulb

Darcy, Daniel P.; Isaacson, Jeffry S.

doi:10.1523/jneurosci.5333-08.2009

Cited by 34 publications

(32 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To this end, we used BayK 8644, a well-characterized positive modulator of L-type VGCCs known to increase their mean open time and to shift the voltage dependence of activation towards more negative potentials 45 . In naive neocortical slices at P3-4, and in line with data from the olfactory bulb 46 , we found that BayK 8644 (20 mM) consistently increased the amplitude of GABA-induced CaTs in the upper CP (DF/F 0 in control: 0.35 ± 0.09, DF/F 0 in BayK 8644: 0.79 ± 0.07, Po0.01, n ¼ 5 slices, paired t-test; Supplementary Fig. 3g-j).…”

Section: Gaba-evoked Cats In Presence Of Bayk 8644 At P3-4supporting

confidence: 81%

GABA depolarizes immature neurons and inhibits network activity in the neonatal neocortex in vivo

et al. 2015

View full text Add to dashboard Cite

A large body of evidence from in vitro studies suggests that GABA is depolarizing during early postnatal development. However, the mode of GABA action in the intact developing brain is unknown. Here we examine the in vivo effects of GABA in cells of the upper cortical plate using a combination of electrophysiological and Ca 2 þ -imaging techniques. We report that at postnatal days (P) 3-4, GABA depolarizes the majority of immature neurons in the occipital cortex of anaesthetized mice. At the same time, GABA does not efficiently activate voltage-gated Ca 2 þ channels and fails to induce action potential firing. Blocking GABA A receptors disinhibits spontaneous network activity, whereas allosteric activation of GABA A receptors has the opposite effect. In summary, our data provide evidence that in vivo GABA acts as a depolarizing neurotransmitter imposing an inhibitory control on network activity in the neonatal (P3-4) neocortex.

show abstract

Section: Gaba-evoked Cats In Presence Of Bayk 8644 At P3-4supporting

confidence: 81%

GABA depolarizes immature neurons and inhibits network activity in the neonatal neocortex in vivo

et al. 2015

View full text Add to dashboard Cite

show abstract

“…In migrating cortical interneurons and cerebellar cells there is an overall correlation between the frequency of [Ca 2ϩ ] i transients and the rate of cell migration (Komuro and Rakic, 1996;Komuro and Kumada, 2005;Bortone and Polleux, 2009). Transient [Ca 2ϩ ] i increments could be triggered by the activation of Gaba and glutamate receptors by ambient neurotransmitters (Owens and Kriegstein, 2002;Luján et al, 2005;Manent et al, 2005;Heng et al, 2007) that may lead to the opening of L-type voltagesensitive calcium channels (Darcy and Isaacson, 2009 Only when a large and maintained [Ca 2ϩ ] i increment is produced, as in the case of caffeine treatment, the link between intracellular calcium, actin remodeling and nuclear movement is revealed. Work in isolated granule cells confronted by a chemorepellent Slit gradient found a Ca 2ϩ wave originated at the leading growth cone that propagates in ϳ10 s to the soma (Guan et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Actomyosin Contraction at the Cell Rear Drives Nuclear Translocation in Migrating Cortical Interneurons

Martini

Valdeolmillos²

2010

Journal of Neuroscience

105

125

View full text Add to dashboard Cite

Neuronal migration is a complex process requiring the coordinated interaction of cytoskeletal components and regulated by calcium signaling among other factors. Migratory neurons are polarized cells in which the largest intracellular organelle, the nucleus, has to move repeatedly. Current views support a central role for pulling forces that drive nuclear movement. The participation of actomyosin driven forces acting at the nucleus rear has been suggested, however its precise contribution has not been directly addressed. By analyzing interneurons migrating in cortical slices of mouse brains, we have found that nucleokinesis is associated with a precise pattern of actin dynamics characterized by the initial formation of a cup-like actin structure at the rear nuclear pole. Time-lapse experiments show that progressive actomyosin contraction drives the nucleus forward. Nucleokinesis concludes with the complete contraction of the cup-like structure, resulting in an actin spot at the base of the retracting trailing process. Our results demonstrate that this actin remodeling requires a threshold calcium level provided by low-frequency spontaneous fast intracellular calcium transients. Microtubule stabilization with taxol treatment prevents actin remodeling and nucleokinesis, whereas cells with a collapsed microtubule cytoskeleton induced by nocodazole treatment, display nearly normal actin dynamics and nucleokinesis. In summary, the results presented here demonstrate that actomyosin forces acting at the rear side of the nucleus drives nucleokinesis in tangentially migrating interneurons in a process that requires calcium and a dynamic cytoskeleton of microtubules.

show abstract

“…Concerning LTCCs as potential modulators of adult neurogenesis and cognition, convincing evidence from in vitro studies [35][36][37][38] and from work on rodent brain slices [39] has demonstrated that immature NSC and NPC carry functional LTCCs. Electrophysiological analyses have confirmed LTCC-induced Ca 2+ currents in subventricular zone derived NSCs and NPCs from embryonic rats [37], in NPCs from postnatal mice [36], and in adult hippocampal NPCs [35].…”

Section: Introductionmentioning

confidence: 99%

The L-type calcium channel Cav1.3 is required for proper hippocampal neurogenesis and cognitive functions

et al. 2015

View full text Add to dashboard Cite

L-type voltage gated Ca(2+) channels (LTCCs) are widely expressed within different brain regions including the hippocampus. The isoforms Cav1.2 and Cav1.3 have been shown to be involved in hippocampus-dependent learning and memory, cognitive functions that require proper hippocampal neurogenesis. In vitro, functional LTCCs are expressed on neuronal progenitor cells, where they promote neuronal differentiation. Expression of LTCCs on neural stem and progenitor cells within the neurogenic regions in the adult brain in vivo has not been examined so far, and a contribution of the individual isoforms Cav1.2 and Cav1.3 to adult neurogenesis remained to be clarified. To reveal the role of these channels we first evaluated the expression patterns of Cav1.2 and Cav1.3 in the hippocampal dentate gyrus and the subventricular zone (SVZ) in adult (2- and 3-month old) and middle-aged (15-month old) mice on mRNA and protein levels. We performed immunohistological analysis of hippocampal neurogenesis in adult and middle-aged Cav1.3(-/-) mice and finally addressed the importance of Cav1.3 for hippocampal function by evaluating spatial memory and depression-like behavior in adult Cav1.3(-/-) mice. Our results showed Cav1.2 and Cav1.3 expression at different stages of neuronal differentiation. While Cav1.2 was primarily restricted to mature NeuN(+) granular neurons, Cav1.3 was expressed in Nestin(+) neural stem cells and in mature NeuN(+) granular neurons. Adult and middle-aged Cav1.3(-/-) mice showed severe impairments in dentate gyrus neurogenesis, with significantly smaller dentate gyrus volume, reduced survival of newly generated cells, and reduced neuronal differentiation. Further, Cav1.3(-/-) mice showed impairment in the hippocampus dependent object location memory test, implicating Cav1.3 as an essential element for hippocampus-associated cognitive functions. Thus, modulation of LTCC activities may have a crucial impact on neurogenic responses and cognition, which should be considered for future therapeutic administration of LTCCs modulators.

show abstract

L-Type Calcium Channels Govern Calcium Signaling in Migrating Newborn Neurons in the Postnatal Olfactory Bulb

Cited by 34 publications

References 37 publications

GABA depolarizes immature neurons and inhibits network activity in the neonatal neocortex in vivo

GABA depolarizes immature neurons and inhibits network activity in the neonatal neocortex in vivo

Actomyosin Contraction at the Cell Rear Drives Nuclear Translocation in Migrating Cortical Interneurons

The L-type calcium channel Cav1.3 is required for proper hippocampal neurogenesis and cognitive functions

Contact Info

Product

Resources

About