Biomedical subjects

Guo-Qiang Bi

Publications and source records attributed to Guo-Qiang Bi.

7 recordsLinked to original sources

PubMed2006

Recent advances in basic neurosciences and brain disease: from synapses to behavior.

Understanding basic neuronal mechanisms hold the hope for future treatment of brain disease. The 1st international conference on synapse, memory, drug addiction and pain was held in beautiful downtown Toronto, Canada on August 21-23, 2006. Unlike other traditional conferences, this new meeting focused on three major aims: (1) to promote new and cutting edge research in neuroscience; (2) to encourage international information exchange and scientific collaborations; and (3) to provide a platform for active scientists to discuss new findings. Up to 64 investigators presented their recent discoveries, from basic synaptic mechanisms to genes related to human brain disease. This meeting was in part sponsored by Molecular Pain, together with University of Toronto (Faculty of Medicine, Department of Physiology as well as Center for the Study of Pain). Our goal for this meeting is to promote future active scientific collaborations and improve human health through fundamental basic neuroscience researches. The second international meeting on Neurons and Brain Disease will be held in Toronto (August 29-31, 2007).

Behavior↗

PubMed2005

Synaptic mechanisms of persistent reverberatory activity in neuronal networks.

For brain functions such as working memory and motor planning, neuronal circuits are able to sustain persistent activity after transient inputs. Theoretical studies have suggested that persistent activity can exist in recurrently connected networks as active reverberation. However, the actual cellular processes underlying such reverberation are not well understood. In this study, we investigated the basic synaptic mechanisms responsible for reverberatory activity in small networks of rat hippocampal neurons in vitro. We found that brief stimulation of one neuron in a network could evoke, in an all-or-none fashion, reverberatory activity lasting for seconds. The reverberation was likely to arise from recurrent excitation because it was eliminated by partial inhibition of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors (but not by blockade of NMDA receptors). In contrast, blocking inhibitory transmission with bicuculline enhanced the reverberation. Furthermore, paired-pulse stimuli with interpulse intervals of 200-400 ms were more effective than single pulses in triggering reverberation, apparently by eliciting higher levels of asynchronous transmitter release. Suppressing asynchronous release by EGTA-AM abolished reverberation, whereas elevating asynchronous release by strontium substantially enhanced reverberation. Finally, manipulating calcium uptake into or release from intracellular stores also modulated the level of reverberation. Thus, the oft-overlooked asynchronous phase of synaptic transmission plays a central role in the emergent phenomenon of network reverberation.

Animals↗

PubMed2005

Coactivation and timing-dependent integration of synaptic potentiation and depression.

Neuronal synaptic connections can be potentiated or depressed by paired pre- and postsynaptic spikes, depending on the spike timing. We show that in cultured rat hippocampal neurons a calcium/calmodulin-dependent protein kinase II (CaMKII)-mediated potentiation process and a calcineurin-mediated depression process can be activated concomitantly by spike triplets or quadruplets. The integration of the two processes critically depends on their activation timing. Depression can cancel previously activated potentiation, whereas potentiation tends to override previously activated depression. The time window for potentiation to dominate is about 70 ms, beyond which the two processes cancel. These results indicate that the signaling machinery underlying spike timing-dependent plasticity (STDP) may be separated into functional modules that are sensitive to the spatiotemporal dynamics (rather than the amount) of calcium influx. The timing dependence of modular interaction provides a quantitative framework for understanding the temporal integration of STDP.

Animals↗

PubMed2005

Timing in synaptic plasticity: from detection to integration.

Timing of cellular and subcellular events contributes to spiking-induced modification of synapses in a variety of ways. Initially, the timing of presynaptic and postsynaptic action potentials must be translated into signals that can initiate intracellular processes. Recent experimental and computational findings suggest that the spatiotemporal details of such signals, in particular the time courses and locations of postsynaptic Ca(2+) transients, might themselves be crucial for driving potentiation and depression modules that interact in a time-dependent way to determine plasticity outcomes. On longer timescales, the effects of multiple spikes are integrated in a nonlinear manner, yielding non-intuitive plasticity results that are likely to be sensitive to local conditions and, finally, additional elements must be called into action to stabilize changes in synaptic strengths. This review is part of the TINS Synaptic Connectivity series.

Action Potentials↗

PubMed2004

Calcium time course as a signal for spike-timing-dependent plasticity.

Calcium has been proposed as a postsynaptic signal underlying synaptic spike-timing-dependent plasticity (STDP). We examine this hypothesis with computational modeling based on experimental results from hippocampal cultures, some of which are presented here, in which pairs and triplets of pre- and postsynaptic spikes induce potentiation and depression in a temporally asymmetric way. Specifically, we present a set of model biochemical detectors, based on plausible molecular pathways, which make direct use of the time course of the calcium signal to reproduce these experimental STDP results. Our model features a modular structure, in which long-term potentiation (LTP) and depression (LTD) components compete to determine final plasticity outcomes; one aspect of this competition is a veto through which appropriate calcium time courses suppress LTD. Simulations of our model are also shown to be consistent with classical LTP and LTD induced by several presynaptic stimulation paradigms. Overall, our results provide computational evidence that, while the postsynaptic calcium time course contains sufficient information to distinguish various experimental long-term plasticity paradigms, small changes in the properties of back-propagation of action potentials or in synaptic dynamics can alter the calcium time course in ways that will significantly affect STDP induction by any detector based exclusively on postsynaptic calcium. This may account for the variability of STDP outcomes seen within hippocampal cultures, under repeated application of a single experimental protocol, as well as for that seen in multiple spike experiments across different systems.

Action Potentials↗

PubMed2002

Synaptic modification in neural circuits: a timely action.

Long-term modification of synaptic strength is thought to be the basic mechanism underlying the activity-dependent refinement of neural circuits and the formation of memories engrammed on them. Studies ranging from cell culture preparations to humans subjects indicate that the decision of whether a synapse will undergo strengthening or weakening critically depends on the temporal order of presynaptic and postsynaptic activity. At many synapses, potentiation will be induced only when the presynaptic neuron fires an action potential within milliseconds before the postsynaptic neuron fires, whereas weakening will occur when it is the postsynaptic neuron that fires first. Such processes might be important for the remodeling of neural circuits by activity during development and for network functions such as sequence learning and prediction. Ultimately, this synaptic property might also be fundamental for the cognitive process by which we structure our experience through cause and effect relations.

Action Potentials↗

PubMed2002

Spatiotemporal specificity of synaptic plasticity: cellular rules and mechanisms.

Recent experimental results on spike-timing-dependent plasticity (STDP) and heterosynaptic interaction in various systems have revealed new temporal and spatial properties of activity-dependent synaptic plasticity. These results challenge the conventional understanding of Hebb's rule and raise intriguing questions regarding the fundamental processes of cellular signaling. In this article, I review these new findings that lead to formulation of a new set of cellular rules. Emphasis is on evaluating potential molecular and cellular mechanisms that may underlie the spike-timing window of STDP and different patterns of heterosynaptic modifications. I also highlight several unresolved issues, and suggest future lines of research.

Action Potentials↗