PubMed Health⌕ Search

Biomedical subjects

Yan Rao

Publications and source records attributed to Yan Rao.

8 recordsLinked to original sources
PubMed2006

Anorectic estrogen mimics leptin's effect on the rewiring of melanocortin cells and Stat3 signaling in obese animals.

Metabolic hormones, such as leptin, alter the input organization of hypothalamic circuits, resulting in increased pro-opiomelanocortin (POMC) tone, followed by decreased food intake and adiposity. The gonadal steroid estradiol can also reduce appetite and adiposity, and it influences synaptic plasticity. Here we report that estradiol (E2) triggers a robust increase in the number of excitatory inputs to POMC neurons in the arcuate nucleus of wild-type rats and mice. This rearrangement of synapses in the arcuate nucleus is leptin independent because it also occurred in leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice, and was paralleled by decreased food intake and body weight gain as well as increased energy expenditure. However, estrogen-induced decrease in body weight was dependent on Stat3 activation in the brain. These observations support the notion that synaptic plasticity of arcuate nucleus feeding circuits is an inherent element in body weight regulation and offer alternative approaches to reducing adiposity under conditions of failed leptin receptor signaling.

Animals↗
PubMed2004

Requirement for the RIIbeta isoform of PKA, but not calcium-stimulated adenylyl cyclase, in visual cortical plasticity.

The cAMP-dependent protein kinase (PKA) signaling pathway plays a key role in visual cortical plasticity. Inhibitors that block activation of all PKA regulatory subunits (RIalpha,RIbeta, RIIalpha, RIIbeta) abolish long-term potentiation (LTP) and long-term depression (LTD) in vitro and ocular dominance plasticity (ODP) in vivo. The details of this signaling cascade, however, including the source of PKA signals and which PKA subunits are involved, are unknown. To investigate these issues we have examined LTP, LTD, and ODP in knock-out mice lacking either the two cortically expressed Ca2+-stimulated adenylyl cyclases (AC1 and AC8) or the predominant neocortical subunit of PKA (RIIbeta). Here we show that plasticity remains intact in AC1/AC8-/- mice, whereas ODP and LTD, but not LTP, are absent in RIIbeta-/- mice. We conclude that (1) plasticity in the visual cortex does not require the activity of known Ca2+-stimulated adenylyl cyclases, (2) the PKA dependence of ODP and LTD, but not LTP, is mediated by RIIbeta-PKA, and (3) multiple isoforms of PKA contribute to LTD.

Adenylyl Cyclases↗
PubMed2004

Layer variations of long-term depression in rat visual cortex.

In vitro long-term depression (LTD) is thought to be a model for the loss of cortical responsiveness to an eye deprived of vision during the critical period. Using whole cell recording, the present study investigates the mechanisms of LTD in vitro across layers in developing rat visual cortex. LTD was induced in layers II/III, V, and VI but not layer IV with 10-min 1-Hz stimulation paired with postsynaptic depolarization. LTD in layers II/III and V could be blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist D-aminophosphonovaleric acid (D-AP5) but not by 100 microM (2S)-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (LY341495), a metabotropic glutamate receptor inhibitor. In contrast, LTD in layer VI was blocked by 100 microM LY341495 and (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) but not D-AP5 and partially blocked by application of guanosine 5'-O-(2-thiodiphosphate) thilothium salt (GDP-beta-S) in patch pipette, suggesting an involvement of postsynaptic group I metabotropic glutamate receptors (mGluRs). These results indicate that LTD in developing rat visual cortex varies with layer: LTD was absent in layer IV, suggesting a unique plasticity mechanism at geniculocortical synapses; LTD in layers II/III and V depends on NMDA receptors but not mGluRs, and LTD in layer VI requires mGluRs but not NMDA receptors.

Animals↗
PubMed2004

LTP and LTD vary with layer in rodent visual cortex.

Mechanisms of plasticity in the visual cortex have been studied with long-term potentiation (LTP), long-term depression (LTD) and ocular dominance plasticity (ODP). It is now possible to compare results from these three forms of plasticity using knockout mice, and also by pharmacological manipulations. A review of the literature shows that if both LTP and LTD are completely abolished, then ODP will also be abolished. In other situations, there is little correlation. We hypothesize that this lack of correlation occurs because the mechanisms for LTP and LTD vary with layer in the visual cortex, and results show that they do.

Animals↗
PubMed2004

Reduced ocular dominance plasticity and long-term potentiation in the developing visual cortex of protein kinase A RII alpha mutant mice.

The cAMP-dependent protein kinase (PKA) signalling pathway has been shown to play an important role in long-term potentiation (LTP) and depression (LTD), and ocular dominance plasticity in the visual cortex. In order to investigate further the involvement of individual PKA subunits in visual cortical plasticity, LTP and LTD in vitro and ocular dominance plasticity in vivo in the developing visual cortex were examined in mice lacking the RII alpha subunit of PKA. Here we show that LTP in layers II/III was decreased in RII alpha knockout mice, but LTD was almost unaffected, and the ocular dominance shift induced by monocular deprivation was also partially blocked. These data provide evidence that RII alpha is involved in LTP and ocular dominance plasticity, and further suggest that different afferent inputs could selectively activate particular subunits of PKA and thereby direct specific aspects of visual cortical plasticity.

Action Potentials↗
PubMed2003

Roles of protein kinase A and protein kinase G in synaptic plasticity in the visual cortex.

Monocular deprivation leads to clear physiological and anatomical changes in the visual cortex known as ocular dominance plasticity. Protein kinase A (PKA) is necessary for ocular dominance plasticity, while protein kinase G (PKG) is not. We have now tested the role of PKA and PKG in long-term potentiation (LTP) and long-term depression (LTD). We have shown that PKA inhibitors have a major effect on both LTP and LTD in the visual cortical slices, whereas a PKG inhibitor affects LTP but not LTD. The PKA activator, 8-chloroadenosine-3',5'-monophosphorothioate, Sp-isomer (Sp-8-Cl-cAMPS), by itself induces a slowly rising form of LTP, which is occluded by theta-burst stimulation (TBS)-induced LTP. These results support the point that the PKA signaling pathway is crucial for neuronal plasticity in visual cortex, and the dissociation of the role of PKA and PKG in long-term synaptic plasticity in the visual cortex suggests that LTP alone is not sufficient to support ocular dominance plasticity, or LTD plays a more fundamental role than LTP in ocular dominance plasticity.

Animals↗
PubMed2002

Involvement of actin cytoskeleton in modulation of Ca(2+)-activated K(+) channels from rat hippocampal CA1 pyramidal neurons.

Using inside-out configuration of patch clamp techniques, actin cytoskeleton modulation of large conductance calcium-activated potassium (BK(Ca)) channels was studied in hippocampal CA1 pyramidal neurons from adult rat. Disruption of actin filament after brief treatment with cytochalasin D (CD) markedly decreased activity of BK(Ca) channels and this inhibitory action persisted even after CD washout. This CD-produced decrease in BK(Ca) channel activity was characterized by a shortened open lifetime and reduced opening frequency. Disruption of actin filament with another toxin cytochalasin B also exerted similar effects as CD. Phalloidin, the actin filament stabilizer, had no significant effect on BK(Ca) channel activity, while pre-treatment with phalloidin could prevent the CD-induced inhibitory effect on channel activity. The present study demonstrates that disruption of actin cytoskeleton can inhibit BK(Ca) channel activity, suggesting that BK(Ca) channels in rat hippocampal CA1 pyramidal neurons may be directly modulated by dynamic assembly and disassembly of submembranous actin cytoskeleton.

Actins↗