Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. gamma-Aminobutyric acid (GABA)-mediated, Cl(-)-dependent inhibitory postsynaptic potentials (IPSPs) and GABA currents in immature rat hippocampal CA1 neurones were studied using the whole-cell recording technique in brain slices. 2. IPSPs evoked by electrical stimulation were observed in postnatal 2- to 5- (PN2-5), 8- to 13-(PN8-13) and 15- to 20-(PN15-20)day-old CA1 neurones. In the presence of glutamate receptor blockers 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and D-2-amino-5-phosphonovaleric acid (APV), the reversal potential for the IPSP (EIPSP) was near the resting membrane potential (RMP) in the PN2-5 neurones, but 13 and 25 mV more negative than the RMP in PN8-13 and PN15-20 neurones respectively. IPSPs and GABA currents were blocked by the GABAA-receptor antagonists bicuculline or picrotoxin. 3. The reversal potential for somatic GABA currents (EGABA) was examined in the presence of tetrodotoxin (TTX). There was a strong dependence of the EGABA upon the patch pipette [Cl-] ([Cl-]p). indicating that the GABA currents were mediated by a Cl- conductance. In PN2-5 neurones, EGABA agreed with the value predicted by the Goldman-Hodgkin-Katz equation at given concentrations of internal and external anions permeable through GABA-activated Cl- channels, whereas EGABA in older neurones was 8-18 mV more negative. 4. Examination of the relations between EGABA, holding potential, [Cl-]p and resting conductance indicated that the membrane of the PN2-5 neurones was readily permeable to Cl- which followed a passive Donnan equilibrium. Passive distribution of Cl- played a decreasing role in PN8-13 neurones and in PN15-20 neurones. 5. To assess the contribution of outward Cl- co-transport, bath applications of high K+ or furosemide were performed. High K+ and furosemide caused a reversible positive shift of EGABA in PN15-20 neurones. Raising the temperature moved EGABA to a more negative potential, with a Q10 of 5 mV. A similar change of EGABA in response to high K+, but not to furosemide, was found in PN8-13 neurones. 6. The present data indicate the existence of GABAA-mediated inhibitory synaptic connections in CA1 neurones at the earliest stages of postnatal life. During the first postnatal week, Cl- ions are passively distributed and the EIPSP and EGABA are near the RMP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Development of GABA-mediated, chloride-dependent inhibition in CA1 pyramidal neurones of immature rat hippocampal slices. 182 51

To evaluate the role of low-voltage-activated (LVA) calcium channels in the lamprey spinal locomotor network, a previous computer simulation model has been extended to include LVA calcium channels. It is also of interest to explore the consequences of a LVA conductance for the electrical behavior of the single neuron. The LVA calcium channel was modeled with voltage-dependent activation and inactivation using the m3h form, following a Hodgkin-Huxley paradigm. Experimental data from lamprey neurons was used to provide parameter values of the single cell model. The presence of a LVA calcium conductance in the model could account for the occurrence of a rebound depolarization in the simulation model. The influence of holding potential on the occurrence of a rebound as well the latency at which it is elicited was investigated and compared with previous experiments. The probability of a rebound increased at a more depolarized holding potential and the latency was also reduced under these conditions. Furthermore, the effect of changing the holding potential and the reversal potential of the calcium dependent potassium conductance were tested to determine under which conditions several rebound spikes could be elicited after a single inhibitory pulse in the simulation model. A reduction of the slow afterhyperpolarization (sAHP) after the action potential reduced the tendency for a train of rebound spikes. The experimental effects of gamma-aminobutyric acid-B (GABA(B)) receptor activation were simulated by reducing the maximal LVA calcium conductance. A reduced tendency for rebound firing and a slower rising phase with sinusoidal current stimulation was observed, in accordance with earlier experiments. The effect of reducing the slow afterhyperpolarization and reducing the LVA calcium current was tested experimentally in the lamprey spinal cord, during N-methyl-D-aspartate (NMDA)-induced fictive locomotion. The reduction of burst frequency was more pronounced with GABA(B) agonists than with apamin (inhibitor of K(Ca) current) when using high NMDA concentration (high burst frequency). The burst frequency increased after the addition of a LVA calcium current to the simulated segmental network, due to a faster recovery during the inhibitory phase as the activity switches between the sides. This result is consistent with earlier experimental findings because GABA(B) receptor agonists reduce the locomotor frequency. These results taken together suggest that the LVA calcium channels contribute to a larger degree with respect to the burst frequency regulation than the sAHP mechanism at higher burst frequencies. The range in which a regular burst pattern can be simulated is extended in the lower range by the addition of LVA calcium channels, which leads to more stable activity at low locomotor frequencies. We conclude that the present model can account for rebound firing and trains of rebound spikes in lamprey neurons. The effects of GABA(B) receptor activation on the network level is consistent with a reduction of the calcium current through LVA calcium channels even though GABA(B) receptor activation will affect the sAHP indirectly and also presynaptic inhibition.
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PMID:Low-voltage-activated calcium channels in the lamprey locomotor network: simulation and experiment. 911 37

The prefrontal cortex (PFC) is critically involved in working memory, which underlies memory-guided, goal-directed behavior. During working-memory tasks, PFC neurons exhibit sustained elevated activity, which may reflect the active holding of goal-related information or the preparation of forthcoming actions. Dopamine via the D1 receptor strongly modulates both this sustained (delay-period) activity and behavioral performance in working-memory tasks. However, the function of dopamine during delay-period activity and the underlying neural mechanisms are only poorly understood. Recently we proposed that dopamine might stabilize active neural representations in PFC circuits during tasks involving working memory and render them robust against interfering stimuli and noise. To further test this idea and to examine the dopamine-modulated ionic currents that could give rise to increased stability of neural representations, we developed a network model of the PFC consisting of multicompartment neurons equipped with Hodgkin-Huxley-like channel kinetics that could reproduce in vitro whole cell and in vivo recordings from PFC neurons. Dopaminergic effects on intrinsic ionic and synaptic conductances were implemented in the model based on in vitro data. Simulated dopamine strongly enhanced high, delay-type activity but not low, spontaneous activity in the model network. Furthermore the strength of an afferent stimulation needed to disrupt delay-type activity increased with the magnitude of the dopamine-induced shifts in network parameters, making the currently active representation much more stable. Stability could be increased by dopamine-induced enhancements of the persistent Na(+) and N-methyl-D-aspartate (NMDA) conductances. Stability also was enhanced by a reduction in AMPA conductances. The increase in GABA(A) conductances that occurs after stimulation of dopaminergic D1 receptors was necessary in this context to prevent uncontrolled, spontaneous switches into high-activity states (i.e., spontaneous activation of task-irrelevant representations). In conclusion, the dopamine-induced changes in the biophysical properties of intrinsic ionic and synaptic conductances conjointly acted to highly increase stability of activated representations in PFC networks and at the same time retain control over network behavior and thus preserve its ability to adequately respond to task-related stimuli. Predictions of the model can be tested in vivo by locally applying specific D1 receptor, NMDA, or GABA(A) antagonists while recording from PFC neurons in delayed reaction-type tasks with interfering stimuli.
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PMID:Dopamine-mediated stabilization of delay-period activity in a network model of prefrontal cortex. 1071 93

Hypocapnia induced by hyperventilation (HV) has powerful effects on neuronal excitability and synaptic transmission. We have studied the effect of hyperventilation on the phase-locked oscillatory components of the evoked responses in the human brain. We recorded visually evoked magnetoencephalographic responses before, during, and after voluntary hyperventilation to pattern-reversal checkerboard stimuli. Gamma-band (30-45 Hz) responses phase-locked to the stimuli were generated in the occipital visual cortex. A wavelet-based time-frequency analysis revealed that the gamma responses increased during HV whereas their frequency did not change significantly. A recent in vitro study in the rat hippocampus demonstrated that the stability of spontaneous gamma activity increases during hypocapnia as a result of enhanced GABAergic transmission. To test if a similar mechanism could account for our findings, we performed simulations on a network of 100 Hodgkin-Huxley neurons connected by inhibitory synapses. We found that enhanced GABA(A) transmission, paired with enhanced excitability, can explain the increase in evoked gamma activity without changing the frequency.
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PMID:Visually evoked gamma responses in the human brain are enhanced during voluntary hyperventilation. 1184

The synchrony of neurons in extrastriate visual cortex is modulated by selective attention even when there are only small changes in firing rate (Fries, Reynolds, Rorie, & Desimone, 2001). We used Hodgkin-Huxley type models of cortical neurons to investigate the mechanism by which the degree of synchrony can be modulated independently of changes in firing rates. The synchrony of local networks of model cortical interneurons interacting through GABA(A) synapses was modulated on a fast timescale by selectively activating a fraction of the interneurons. The activated interneurons became rapidly synchronized and suppressed the activity of the other neurons in the network but only if the network was in a restricted range of balanced synaptic background activity. During stronger background activity, the network did not synchronize, and for weaker background activity, the network synchronized but did not return to an asynchronous state after synchronizing. The inhibitory output of the network blocked the activity of pyramidal neurons during asynchronous network activity, and during synchronous network activity, it enhanced the impact of the stimulus-related activity of pyramidal cells on receiving cortical areas (Salinas & Sejnowski, 2001). Synchrony by competition provides a mechanism for controlling synchrony with minor alterations in rate, which could be useful for information processing. Because traditional methods such as cross-correlation and the spike field coherence require several hundred milliseconds of recordings and cannot measure rapid changes in the degree of synchrony, we introduced a new method to detect rapid changes in the degree of coincidence and precision of spike timing.
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PMID:Rapid temporal modulation of synchrony by competition in cortical interneuron networks. 1500 96

Voltage-gated K+ channels perform many functions in integration of synaptic input and action potential (AP) generation. In this study we show that in bitufted interneurones from layer 2/3 of the somatosensory cortex, the height and width of APs recorded at the soma are sensitive to changes in the resting membrane potential, suggesting subthreshold activity of voltage-gated conductances. Attributes of K+ currents examined in nucleated patches revealed a fast subthreshold-inactivating K+ conductance (K(f)) and a slow suprathreshold-inactivating K+ conductance (K(s)). Simulations of these K+ conductances, incorporated into a Hodgkin-Huxley-type model, suggested that during a single AP or during low frequency trains of APs, subthreshold inactivation of K(f) was the primary modulator of AP shape, whereas during trains of APs the shape was governed to a larger degree by K(s) resulting in the generation of smaller and broader APs. Utilizing the facilitating function of unitary pyramidal-to-bitufted cell synaptic transmission, single back-propagating APs were initiated in a bitufted interneurone by repeated stimulation of a presynaptic pyramidal cell. Ca2+ imaging and dendritic whole-cell recordings revealed that modulation of APs, which also affect the shape of back-propagating APs, resulted in a change in dendritic Ca2+ influx. Compartmental simulation of the back-propagating AP suggested a mechanism for the modulation of the back-propagating AP height and width by subthreshold activation of K(f). We speculate that this signal may modulate retrograde GABA release and consequently depression of synaptic efficacy of excitatory input from neighbouring pyramidal neurones.
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PMID:Subthreshold inactivation of voltage-gated K+ channels modulates action potentials in neocortical bitufted interneurones from rats. 1553 96

Afferent neurons entering the central nervous systems of vertebrates and invertebrates receive presynaptic inhibition on their axon terminals. This usually involves an increase in membrane conductance (shunting) and depolarization (primary afferent depolarization, PAD). In arachnids and crustaceans the peripherally located parts of afferent neurons also receive efferent synapses. GABA (gamma-aminobutyric acid) plays a major role in both central and peripheral inhibition, activating chloride channels that depolarize the membrane and increase its conductance. Although both central and peripheral inhibition have been widely investigated, debate continues about the mechanisms involved, especially concerning the relative contributions of shunting versus inactivation of sodium channels by depolarization. Sensory neurons innervating spider VS-3 slit sensilla are accessible to intracellular recordings during mechanical or electrical stimulation. These neurons are inhibited by GABA, and both the electrophysiology and pharmacology of this inhibition have been studied previously. Here, we developed a Hodgkin-Huxley style model to simulate VS-3 neuron activity before and after GABA treatment. The model indicates that GABA-activated chloride current can entirely account for action potential suppression, and that either shunting or inactivation are sufficient to produce inhibition. This model also demonstrates that slowing of sodium current contributes to inhibition.
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PMID:Shunting versus inactivation: simulation of GABAergic inhibition in spider mechanoreceptors suggests that either is sufficient. 1661 90

Neural circuits controlling fast movements are inherently unsteady as a result of their reciprocal innervation. This instability is enhanced by increased membrane excitability. Recent studies indicate that the loss of external inhibition is an important factor in the pathogenesis of several tremor disorders such as essential tremor, cerebellar kinetic tremor or parkinsonian tremor. Shaikh and colleagues propose a new conceptual scheme to analyze tremor disorders. Oscillations are simulated by changing the intrinsic membrane properties of burst neurons. The authors use a model neuron of Hodgkin-Huxley type with added hyperpolarization activated cation current (Ih), low threshold calcium current (It), and GABA/glycine mediated chloride currents. Post-inhibitory rebound is taken into account. The model includes a reciprocally innervated circuit of neurons projecting to pairs of agonist and antagonist muscles. A set of four burst neurons has been simulated: inhibitory agonist, inhibitory antagonist, excitatory agonist, and excitatory antagonist. The model fits well with the known anatomical organization of neural circuits for limb movements in premotor/motor areas, and, interestingly, this model does not require any structural modification in the anatomical organization or connectivity of the constituent neurons. The authors simulate essential tremor when Ih is increased. Membrane excitability is augmented by up-regulating Ih and It. A high level of congruence with the recordings made in patients exhibiting essential tremor is reached. These simulations support the hypothesis that increased membrane excitability in potentially unsteady circuits generate oscillations mimicking tremor disorders encountered in daily practice. This new approach opens new perspectives for both the understanding and the treatment of neurological tremor. It provides the rationale for decreasing membrane excitability by acting on a normal ion channel in a context of impaired external inhibition.
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PMID:Tremorgenesis: a new conceptual scheme using reciprocally innervated circuit of neurons. 1903 42

Propofol, like most general anesthetic drugs, can induce both behavioral and electroencephalographic (EEG) manifestations of excitation, rather than sedation, at low doses. Neuronal excitation is unexpected in the presence of this GABA(A)-potentiating drug. We construct a series of network models to understand this paradox. Individual neurons have ion channel conductances with Hodgkin-Huxley-type formulations. Propofol increases the maximal conductance and time constant of decay of the synaptic GABA(A) current. Networks range in size from 2 to 230 neurons. Population output is measured as a function of pyramidal cell activity, with the electroencephalogram approximated by the sum of population AMPA activity between pyramidal cells. These model networks suggest propofol-induced paradoxical excitation may result from a membrane level interaction between the GABA(A) current and an intrinsic membrane slow potassium current (M-current). This membrane level interaction has consequences at the level of multicellular networks enabling a switch from baseline interneuron synchrony to propofol-induced interneuron antisynchrony. Large network models reproduce the clinical EEG changes characteristic of propofol-induced paradoxical excitation. The EEG changes coincide with the emergence of antisynchronous interneuron clusters in the model networks. Our findings suggest interneuron antisynchrony as a potential network mechanism underlying the generation of propofol-induced paradoxical excitation. As correlates of behavioral phenomenology, these networks may refine our understanding of the specific behavioral states associated with general anesthesia.
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PMID:Potential network mechanisms mediating electroencephalographic beta rhythm changes during propofol-induced paradoxical excitation. 1907 22

We review the neuronal antibodies described in CNS disorders in order to clarify their diagnostic value, emphasize potentials pitfalls and limitations in the diagnosis of paraneoplastic neurological syndromes (PNS), and examine the current evidence for a possible pathogenic role. We propose to classify the neuronal antibodies associated with syndromes resulting from CNS neuronal dysfunction into two groups according to the location of the antigen: inside the neuron or in the cell membrane. Group I includes antibodies which target intracellular antigens and probably are not pathogenic. They are further subdivided into three groups. Group Ia comprises well-characterized onconeural antibodies (Hu (ANNA1), Yo (PCA1), Ri (ANNA2), CV2 (CRMP5), amphiphysin, Ma2) that are useful for the diagnosis of PNS. Group Ib antibodies (SOX and ZIC) are cancer-specific but there is no evidence that the immune response is in any way pathogenically related to the PNS. Antibodies in group Ic (glutamic acid decarboxylase (GAD), adenylate kinase 5 and Homer 3) identify non-PNS: stiff-person syndrome (SPS), cerebellar ataxia, and limbic encephalitis (LE). Group II antibodies recognize neuronal surface antigens. Antibodies in group IIa associate with characteristic CNS syndromes but their detection does not indicate that the disorder is paraneoplastic. Antibodies to potassium channels, AMPA and GABA(B) receptors are associated with LE, NMDA receptor antibodies identify a well-defined encephalitis, and antibodies against glycine receptors associate with SPS with encephalitis. A pathogenic role of the antibodies is suggested by the response of symptoms to immunotherapy and the correlation between antibody titers and neurological outcome. Lastly, Group IIb includes antibodies that are found in patients with paraneoplastic cerebellar ataxia associated with lung cancer (P/Q type calcium channels antibodies) or Hodgkin disease (metabotropic glutamate receptor type 1 antibodies).
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PMID:Antibodies and neuronal autoimmune disorders of the CNS. 2003 30


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