Biomedical subjects

Yousheng Shu

Publications and source records attributed to Yousheng Shu.

10 recordsLinked to original sources

PubMed2007

Factors influencing cell fate in the infarct rim.

In focal ischemia, the fate of penumbral cells is closely linked to the infarcted tissue. Because of the release of cytosolic material from damaged cells, the biochemical and ionic alterations within the core are dramatic. Hence, adjacent cells ( infarct rim) are generally exposed to these changes and may be deleteriously affected. To mimic such conditions in vitro, we have employed a slice culture system and used an ischemic solution (IS) that resembles the milieu in the territory of infarct rim. In contrast to normal artificial cerebral spinal fluid, IS is characterized by low O(2), glucose, pH; excitotoxic levels of glutamate; and ionic alterations. In organotypic hippocampal slice cultures, we examined cell injury/death using propidium iodide following exposure to IS. Our data show significant cell injury starting at approximately 8 h following IS exposure with cell injury spreading as a function of exposure duration. We further studied the effect of each component in the IS separately, i.e., acidosis, hypoxia, ionic shifts or glutamate exitotoxicity and were able to isolate the contribution of each of these effectors to the IS-induced cell death. Our results suggest that in IS, acidosis exacerbates the potential for injury while ionic shifts, especially those of K(+) and Na(+), alleviate the potential for cell death.

Animals↗

PubMed2007

Neurophysiology: Hodgkin and Huxley model--still standing?

Action potentials in cortical neurons show a variable threshold and a sudden rise in membrane potential at initiation. Naundorf et al. fail to explain these features using single- or double-compartment Hodgkin-Huxley-style models, suggesting instead that they could arise from cooperative opening of Na+ channels, although there is no direct biological evidence to support this. Here we show that these so-called unique features are to be expected from Hodgkin-Huxley models if the spatial geometry and spike initiation properties of cortical neurons are taken into account--it is therefore unnecessary to invoke exotic channel-gating properties as an explanation.

Action Potentials↗

PubMed2006

Properties of action-potential initiation in neocortical pyramidal cells: evidence from whole cell axon recordings.

Cortical pyramidal cells are constantly bombarded by synaptic activity, much of which arises from other cortical neurons, both in normal conditions and during epileptic seizures. The action potentials generated by barrages of synaptic activity may exhibit a variable site of origin. Here we performed simultaneous whole cell recordings from the soma and axon or soma and apical dendrite of layer 5 pyramidal neurons during normal recurrent network activity (up states), the intrasomatic or intradendritic injection of artificial synaptic barrages, and during epileptiform discharges in vitro. We demonstrate that under all of these conditions, the real or artificial synaptic bombardments propagate through the dendrosomatic-axonal arbor and consistently initiate action potentials in the axon initial segment that then propagate to other parts of the cell. Action potentials recorded intracellularly in vivo during up states and in response to visual stimulation exhibit properties indicating that they are typically initiated in the axon. Intracortical axons were particularly well suited to faithfully follow the generation of action potentials by the axon initial segment. Action-potential generation was more reliable in the distal axon than at the soma during epileptiform activity. These results indicate that the axon is the preferred site of action-potential initiation in cortical pyramidal cells, both in vivo and in vitro, with state-dependent back propagation through the somatic and dendritic compartments.

Action Potentials↗

PubMed2006

Modulation of intracortical synaptic potentials by presynaptic somatic membrane potential.

Traditionally, neuronal operations in the cerebral cortex have been viewed as occurring through the interaction of synaptic potentials in the dendrite and soma, followed by the initiation of an action potential, typically in the axon. Propagation of this action potential to the synaptic terminals is widely believed to be the only form of rapid communication of information between the soma and axonal synapses, and hence to postsynaptic neurons. Here we show that the voltage fluctuations associated with dendrosomatic synaptic activity propagate significant distances along the axon, and that modest changes in the somatic membrane potential of the presynaptic neuron modulate the amplitude and duration of axonal action potentials and, through a Ca2+-dependent mechanism, the average amplitude of the postsynaptic potential evoked by these spikes. These results indicate that synaptic activity in the dendrite and soma controls not only the pattern of action potentials generated, but also the amplitude of the synaptic potentials that these action potentials initiate in local cortical circuits, resulting in synaptic transmission that is a mixture of triggered and graded (analogue) signals.

Action Potentials↗

PubMed2005

Inhibitory postsynaptic potentials carry synchronized frequency information in active cortical networks.

Temporal precision in spike timing is important in cortical function, interactions, and plasticity. We found that, during periods of recurrent network activity (UP states), cortical pyramidal cells in vivo and in vitro receive strong barrages of both excitatory and inhibitory postsynaptic potentials, with the inhibitory potentials showing much higher power at all frequencies above approximately 10 Hz and more synchrony between nearby neurons. Fast-spiking inhibitory interneurons discharged strongly in relation to higher-frequency oscillations in the field potential in vivo and possess membrane, synaptic, and action potential properties that are advantageous for transmission of higher-frequency activity. Intracellular injection of synaptic conductances having the characteristics of the recorded EPSPs and IPSPs reveal that IPSPs are important in controlling the timing and probability of action potential generation in pyramidal cells. Our results support the hypothesis that inhibitory networks are largely responsible for the dissemination of higher-frequency activity in cortex.

Action Potentials↗

PubMed2003

Barrages of synaptic activity control the gain and sensitivity of cortical neurons.

Ongoing synaptic activity, ever present in cortical neurons, may vary widely in its amplitude and characteristics, potentially having a strong influence on neuronal processing. Intracellular recordings in layer 5 pyramidal cells in prefrontal and visual cortical slices maintained in vitro revealed spontaneous periods of synaptic bombardment. Testing the responsiveness of these cortical cells to synaptic inputs or the injection of artificial excitatory postsynaptic conductances of various amplitudes revealed that background synaptic activity dramatically increased the probability of response to small inputs, decreased the slope of the input-output curve, and decreased both the latency and jitter of action potential activation. Examining the effects of different components of synaptic barrages (namely, depolarization, increase in membrane conductance, and increase in membrane potential variance) revealed that the effects observed were dominated by the membrane depolarization and increase in variance. Depolarization increased the peak cross-correlation between injected complex in vivo-like waveforms through enhancement of responsiveness to small inputs, whereas increases in variance did so through a shift in firing mode from one of threshold detection to probabilistic discharge. These results indicate that rapid increases in neuronal responsiveness, as well as increases in spike timing precision, can be achieved through balanced barrages of excitatory and inhibitory synaptic activity.

Action Potentials↗

PubMed2003

Turning on and off recurrent balanced cortical activity.

The vast majority of synaptic connections onto neurons in the cerebral cortex arise from other cortical neurons, both excitatory and inhibitory, forming local and distant 'recurrent' networks. Although this is a basic theme of cortical organization, its study has been limited largely to theoretical investigations, which predict that local recurrent networks show a proportionality or balance between recurrent excitation and inhibition, allowing the generation of stable periods of activity. This recurrent activity might underlie such diverse operations as short-term memory, the modulation of neuronal excitability with attention, and the generation of spontaneous activity during sleep. Here we show that local cortical circuits do indeed operate through a proportional balance of excitation and inhibition generated through local recurrent connections, and that the operation of such circuits can generate self-sustaining activity that can be turned on and off by synaptic inputs. These results confirm the long-hypothesized role of recurrent activity as a basic operation of the cerebral cortex.

Action Potentials↗

PubMed2003

Persistent cortical activity: mechanisms of generation and effects on neuronal excitability.

Local cortical networks in the prefrontal cortex and visual cortex are capable of spontaneously generating sustained activity for periods of seconds or longer. This sustained activity is generated through recurrent excitation between pyramidal cells that is controlled by feedback inhibition and can have both a rapid onset and a rapid offset. The period of activity is associated with a marked increase in neuronal responsiveness to the intracellular injection of current pulses, especially those of smaller amplitude. Independently mimicking the depolarization, increase in membrane conductance and increase in noise associated with sustained activity revealed that the depolarization is largely responsible for the increase in neuronal responsiveness, although an increase in membrane noise also facilitates responses to small inputs. These results indicate that the persistent activity associated with the performance of working memory tasks may be generated largely through recurrent networks. They also suggest that feedback pathways, such as those involved in selective attention, may exert a powerful influence on neuronal responsiveness through synaptic bombardment.

Action Potentials↗

PubMed2002

Similar electrophysiological changes in axotomized and neighboring intact dorsal root ganglion neurons.

We investigated electrophysiological changes in chronically axotomized and neighboring intact dorsal root ganglion (DRG) neurons in rats after either a peripheral axotomy consisting of an L5 spinal nerve ligation (SNL) or a central axotomy produced by an L5 partial rhizotomy (PR). SNL produced lasting hyperalgesia to punctate indentation and tactile allodynia to innocuous stroking of the foot ipsilateral to the injury. PR produced ipsilateral hyperalgesia without allodynia with recovery by day 10. Intracellular recordings were obtained in vivo from the cell bodies (somata) of axotomized and intact DRG neurons, some with functionally identified peripheral receptive fields. PR produced only minor electrophysiological changes in both axotomized and intact somata in L5 DRG. In contrast, extensive changes were observed after SNL in large- and medium-sized, but not small-sized, somata of intact (L4) as well as axotomized (L5) DRG neurons. These changes included (in relation to sham values) higher input resistance, lower current and voltage thresholds, and action potentials with longer durations and slower rising and falling rates. The incidence of spontaneous activity, recorded extracellularly from dorsal root fibers in vitro, was significantly higher (in relation to sham) after SNL but not after PR, and occurred in myelinated but not unmyelinated fibers from both L4 (9.1%) and L5 (16.7%) DRGs. We hypothesize that the changes in the electrophysiological properties of axotomized and intact DRG neurons after SNL are produced by a mechanism associated with Wallerian degeneration and that the hyperexcitability of intact neurons may contribute to SNL-induced hyperalgesia and allodynia.

Acute Disease↗

PubMed2002

Inhibitory interactions between ferret thalamic reticular neurons.

The thalamic reticular nucleus (nRt) provides an important inhibitory input to thalamic relay nuclei and is central in the generation of both normal and abnormal thalamocortical activities. Although local inhibitory interactions between these neurons may play an important role in controlling thalamocortical activities, the physiological features of this interaction have not been fully investigated. Here we sought to establish the nature of inhibitory interaction between nRt neurons with intracellular and extracellular recordings in slices of ferret nRt maintained in vitro. In many nRt neurons, intracellular recordings revealed spontaneous inhibitory postsynaptic potentials (IPSPs). In addition, the local excitation of nRt cells with glutamate led to the generation of IPSPs in the intracellularly recorded nRt neuron. These evoked IPSPs exhibited an average reversal potential of -72 mV and could be blocked by picrotoxin, a GABA(A)-receptor antagonist. These results indicate that nRt neurons interact locally through the activation of GABA(A) receptor-mediated inhibitory postsynaptic potentials. This lateral inhibition may play an important role in controlling the responsiveness of these cells to cortical and thalamic excitatory inputs in both normal and abnormal thalamocortical function.

Action Potentials↗