Biomedical subjects

Yupeng Yang

Publications and source records attributed to Yupeng Yang.

8 recordsLinked to original sources

PubMed2005

Experience-driven plasticity of visual cortex limited by myelin and Nogo receptor.

Monocular deprivation normally alters ocular dominance in the visual cortex only during a postnatal critical period (20 to 32 days postnatal in mice). We find that mutations in the Nogo-66 receptor (NgR) affect cessation of ocular dominance plasticity. In NgR-/- mice, plasticity during the critical period is normal, but it continues abnormally such that ocular dominance at 45 or 120 days postnatal is subject to the same plasticity as at juvenile ages. Thus, physiological NgR signaling from myelin-derived Nogo, MAG, and OMgp consolidates the neural circuitry established during experience-dependent plasticity. After pathological trauma, similar NgR signaling limits functional recovery and axonal regeneration.

Animals↗

PubMed2005

Reversible blockade of experience-dependent plasticity by calcineurin in mouse visual cortex.

Numerous protein kinases have been implicated in visual cortex plasticity, but the role of serine/threonine protein phosphatases has not yet been established. Calcineurin, the only known Ca2+/calmodulin-activated protein phosphatase in the brain, has been identified as a molecular constraint on synaptic plasticity in the hippocampus and on memory. Using transgenic mice overexpressing calcineurin inducibly in forebrain neurons, we now provide evidence that calcineurin is also involved in ocular dominance plasticity. A transient increase in calcineurin activity is found to prevent the shift of responsiveness in the visual cortex following monocular deprivation, and this effect is reversible. These results imply that the balance between protein kinases and phosphatases is critical for visual cortex plasticity.

Aging↗

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

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

Non-dominant eye responses in the dorsal lateral geniculate nucleus of the cat: an intracellular study.

UNLABELLED: While binocularity has been established as an important characteristic of cat visual cortical neurons, neurons in the dorsal lateral geniculate nucleus (LGNd) are commonly believed to be monocular. To test whether binocularity exists at the level of the LGNd, postsynaptic potentials (PSPs) of 101 cells were intracellularly recorded in eight normal and eight monocularly deprived cats while presenting stimuli to either the dominant or non-dominant eyes. The results showed that: (1) About 92% of neurons (45 out of 49) responded to a flashing spot presented to the non-dominant eye. In contrast to the dominant eye responses, the non-dominant eye PSPs usually exhibited the same polarization tendency (hyperpolarization or depolarization) to flashing spot stimuli of light increment or decrement, and most of them were inhibitory (hyperpolarization, 35 out of 45, 78%). (2) The response field (RF) of the non-dominant eye overlapped that of the dominant eye. (3) For most binocular cells, peak-to-peak amplitudes of non-dominant eye PSPs were about half the size (46%) of those of the dominant eye. The peak latencies and half-peak latencies of non-dominant eye PSPs were significantly longer than those of the dominant eye (mean differences were 5.4 ms and 5.6 ms respectively). (4) Most of the binocular cells responded well to contrast reversing gratings presented to the non-dominant eye, and the responses were clearly spatial-frequency tuned. No null phase could be found for non-dominant eye PSPs, no matter the neuron was classified as X or Y type according to dominant eye elicited responses. Some of the cells responded well to drifting gratings presented to the non-dominant eye. (5) We also recorded 52 cells in monocularly deprived cats, and found that 49 cells (94%) showed significant responses to flashing spots presented to the non-dominant eye, a similar percentage to that found in normal cats (92%). CONCLUSION: as strongly monocular neurons, most of LGNd cells could also be driven by the non-dominant eye. The responses evoked by non-dominant eye stimulation differ greatly from those evoked by dominant eye stimulation, and remain intact even without visual experience. These observations suggest an important role of the perigeniculate nucleus in providing binocular inputs to LGNd cells.

Action Potentials↗

PubMed2003

Blockade of cyclic AMP-dependent protein kinase does not prevent the reverse ocular dominance shift in kitten visual cortex.

Monocular deprivation (MD) during the critical period for the development of visual cortex causes a loss of binocular response of neurons and a shift to the open eye, a normal ocular dominance (OD) shift. However, when MD is combined with chronic inactivation of the visual cortex by muscimol, the OD distribution of the neurons shifts to the deprived eye (reverse OD shift). We have previously shown that the normal OD shift is abolished by chronic infusion of the protein kinase A (PKA) inhibitor, 8-chloroadenosine-3', 5'-cyclic monophosphorothioate, Rp-isomer (Rp-8-Cl-cAMPS), into kitten visual cortex. In this study, we investigated the effect of this inhibitor on the reverse OD shift. Combination of MD and muscimol infusion into the visual cortex of 6-wk-old kittens caused a reverse OD shift that was comparable to that seen in previous studies. However, a reverse OD shift was also seen with concurrent infusion of the PKA inhibitor with muscimol. The strongest OD shift was observed in layer IV regardless of the presence or absence of the PKA inhibitor. This suggests that the dissociation of pre- and postsynaptic activities, which occurs mainly at thalamocortical synapses, induces the reverse OD shift and that inhibition of PKA does not prevent it. Presumably, an inhibition of PKA has no effect in silent cortex. We conclude that 1) an activation of PKA is not required for the induction of the reverse OD shift, and 2) the intracellular signaling mechanism underlying MD-induced OD plasticity differs between normal and reverse OD shifts.

Animals↗

PubMed2003

GABA(A) and GABA(B) receptors mediated inhibition affect the pattern adaptation of relay cells in the dorsal lateral geniculate nucleus (LGNd) of cats.

Pattern adaptation is very important for visual function, while the mechanisms that mediate pattern adaptation, especially in the dorsal lateral geniculate nucleus (LGNd), are still unclear. Iontophoresis of the antagonists and agonists of GABA receptors were employed to separately investigate the contribution of GABA(A) and GABA(B) receptors to pattern adaptation of LGNd cells. When GABA(A) receptors were blocked by bicuculline both the response amplitude of LGNd cells and the degree of adaptation increased significantly. Many neurons showing no pattern adaptation under the normal condition became adapted to a prolonged stimulus. Moreover, the proportion of cells showing adaptation doubled (from 40 to 88%). The mean adaptation index (AI, adapted response amplitude/original response amplitude) was 0.82 during bicuculline application, compared with 0.92 under the control condition. In additional, iontophoresis of baclofen, a selective GABA(B) receptor agonist, decreased the mean response amplitude to grating stimuli to 53% of normal. Nearly half of the neurons increased their adaptation index following baclofen administration and the mean AI increased from 0.89 to 1.01. Iontophoresis of GABA(B) receptor antagonist (CGP35348) could abolish this effect, though it had no significant effect on visual response amplitude and pattern adaptation itself. Iontophoresis of another GABA(B) receptor antagonist, 2-OH-saclofen, also had no significant effect on visual response amplitude and pattern adaptation. These results suggest that both GABA(A) receptors and GABA(B) receptors modulate the pattern adaptation of LGNd cells and are involved in synaptic plasticity.

Action Potentials↗