Biomedical subjects

Min-Xu Li

Publications and source records attributed to Min-Xu Li.

4 recordsLinked to original sources

PubMed2004

The role of the theta isoform of protein kinase C (PKC) in activity-dependent synapse elimination: evidence from the PKC theta knock-out mouse in vivo and in vitro.

PKC plays a critical role in competitive activity-dependent synapse modification at the neuromuscular synapse in vitro and in vivo. This action involves a reduction of the strength of inactive inputs to muscle cells that are activated by other inputs. A decrease of postsynaptic responsiveness and a loss of postsynaptic acetyl choline receptors account for the heterosynaptic loss in vitro. The loss is not seen in preparations in which PKC has been blocked pharmacologically. Here, we show that the loss does not occur in in vitro preparations made from animals genetically modified to lack the theta isoform of PKC. Synapse elimination in the newborn period in vivo is delayed but is eventually expressed in knock-out animals. PKC-dependent synapse reduction is suppressed in heterologous cultures combining normal nerve and PKC theta-deficient muscle, as might be expected from the postsynaptic locus of the changes that underlie the activity-dependent plasticity. Preparations in which PKC theta-deficient neurons innervated normal muscle also exhibited a marked deficit in PKC-deficient synapse reduction. The presynaptic action of PKC theta implied by this observation is blocked by TTX, and we propose that activity-related synapse strengthening is decreased by presynaptic PKC theta. Thus, PKC theta in both presynaptic and postsynaptic elements plays a critical role in activity-dependent synapse modulation and loss. We provide a model for activity-dependent synapse loss incorporating these findings.

Animals↗

PubMed2003

Protein kinases and Hebbian function.

The Hebb synapse, in which the strength of synapses is affected by activity in presynaptic and postsynaptic nerve cells, is a widely used model for developmental and learning-related neuroplasticity. Presynaptic and postsynaptic firing that is correlated in time is postulated to increase synaptic strength while activity in presynaptic and postsynaptic neurons that is not correlated results in weakening. The authors describe a cell biologic, mechanistic model for activity-dependent modification of synapse strength that selectively weakens inactive inputs to activated targets. Differentially localized protein kinase A and protein kinase C molecules are activated by spike and synaptic activity. Subsequent kinase-specific phosphorylation and stabilization or destabilization of synaptic receptors are molecular and cell biologic substrates of the Hebb synapse.

Animals↗

PubMed2002

Pre- and postsynaptic mechanisms in Hebbian activity-dependent synapse modification.

We have used a three compartment tissue culture system that involved two separate populations of cholinergic neurons in the side compartments that converged on a common target population of myotubes in the center compartment. Activation of the axons from one population of neurons produced selective down-regulation of the synaptic inputs from the other neuronal population (when the two inputs innervated the same myotubes). The decrease in heterosynaptic inputs was mediated by protein kinase C (PKC). An activity-dependent action of protein kinase A (PKA) was associated with the stimulated input and this served to selectively stabilize this input. These changes associated with PKA and PKC activation were mediated by alterations in the number of acetylcholine receptors at the neuromuscular junction. These results suggest that neuromuscular electrical activity produces postsynaptic activation of both PKA and PKC, with the latter producing generalized synapse weakening and the former a selective synapse stabilization. Treatment of the neuronal cell body and axon to increase PKC activity by putting phorbal ester (PMA) in the side chamber did not affect synaptic transmission (with or without stimulation). By contrast, PKA blockade in the side compartment did produce an activity-dependent decrease in synaptic efficacy, which was due to a decrease in quantal release of neurotransmitter. Thus, when the synapse is activated, it appears that presynaptic PKA action is necessary to maintain transmitter output.

Animals↗

PubMedDate not supplied

Phosphorylation reactions in activity-dependent synapse modification at the neuromuscular junction during development.

We have studied developmental activity-dependent synapse diminution in both an in vitro tissue culture chamber system and at the intact rodent neuromuscular junction (nmj). In both types of preparations, pre- and postsynaptic alterations in synapse structure and function are produced by manipulations of thrombin (Thr) and protein kinase C (PKC) activity. An opposing postsynaptic effect of PKC and protein kinase A (PKA) action on the acetycholine receptor (AChR) can be shown in vitro with PKA stabilizing and PKC destabilizing the nmj synapses. In vivo studies of normal junctional maturation show that changes in axonal inputs and postsynaptic receptor cluster morphology occur, to a substantial degree, independently of one another. Presynaptic actions of PKA are involved in the activity dependent synapse modulation that can be demonstrated in vitro. Late in the elimination process, (>12 days in vivo ) the process becomes independent of PKC, implying that diverse, redundant mechanisms are involved in this important developmental process.

Action Potentials↗