Jason A Justice

Texas A&M University System Health Science Center, Bryan, Texas, United States

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Publications (4)16.35 Total impact

  • Bi-Wen Peng · Jason A Justice · Xiao-Hua He · Russell M Sanchez ·
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    ABSTRACT: Cerebral hypoxia is a major cause of neonatal seizures, and can lead to epilepsy. Pathologic anatomic and physiologic changes in the dentate gyrus have been associated with epileptogenesis in many experimental models, as this region is widely believed to gate the propagation of limbic seizures. However, the consequences of hypoxia-induced seizures for the immature dentate gyrus have not been extensively examined. Seizures were induced by global hypoxia (5-7% O2 for 15 min) in rat pups on postnatal day 10. Whole-cell voltage-clamp recordings were used to examine A-type potassium currents (IA ) in dentate granule cells in hippocampal slices obtained 1-17 days after hypoxia treatment. Seizure-inducing hypoxia resulted in decreased maximum IA amplitude in dentate granule cells recorded within the first week but not at later times after hypoxia treatment. The decreased IA amplitude was not associated with changes in the voltage-dependence of activation or inactivation removal, or in sensitivity to inhibition by 4-aminopyridine (4-AP). However, consistent with the role of IA in shaping firing patterns, we observed in the hypoxia group a significantly decreased latency to first spike with depolarizing current injection from hyperpolarized potentials. These differences were not associated with changes in resting membrane potential or input resistance, and were eliminated by application of 10 m 4-AP. Given the role of IA to slow action potential firing, decreased IA could contribute to long-term hippocampal pathology after neonatal seizure-inducing hypoxia by increasing dentate granule cell excitability during a critical window of activity-dependent hippocampal maturation.
    Epilepsia 07/2013; 54(7):1223-31. DOI:10.1111/epi.12150 · 4.57 Impact Factor
  • Bi-Wen Peng · Jason A Justice · Kun Zhang · Jun-Xu Li · Xiao-Hua He · Russell M Sanchez ·
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    ABSTRACT: The H-current (I(H)) regulates membrane electrical activity in many excitable cells. The antiepileptic drug gabapentin (GBP) has been shown to increase I(H) in hippocampal area CA1 pyramidal neurons, and this has been proposed as an anticonvulsant mechanism of action. I(H) also regulates excitability in some types of hippocampal interneuron that provide synaptic inhibition to CA1 pyramidal neurons, suggesting that global pharmacological I(H) enhancement could have more complex effects on the local synaptic network. However, whether I(H) in CA1 interneurons is modulated by GBP has not been examined. In this study, we tested the effects of GBP on I(H) on hippocampal area CA1 stratum oriens non-pyramidal neurons, and on spontaneous inhibitory postsynaptic currents (sIPSCs) in CA1 pyramidal neurons in immature rat brain slices. GBP (100μM) increased I(H) in approximately 67% of interneurons that exhibited I(H), with no apparent effect on cell types that did not exhibit I(H). GBP also increased the frequency of spontaneous (but not miniature) inhibitory postsynaptic currents in pyramidal neurons without altering amplitudes or rise and decay times. These data indicate that I(H) in a subset of CA1 interneuron types can be increased by GBP, similarly to its effect on I(H) in pyramidal neurons, and further, that indirectly increased spontaneous inhibition of pyramidal neurons could contribute to its anticonvulsant effects.
    Neuroscience Letters 02/2011; 494(1):19-23. DOI:10.1016/j.neulet.2011.02.045 · 2.03 Impact Factor
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    Bi-Wen Peng · Jason A Justice · Kun Zhang · Xiao-hua He · Russell M Sanchez ·
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    ABSTRACT: The hyperpolarization-activated cation current (IH) regulates the electrical activity of many excitable cells, but its precise function varies across cell types. The antiepileptic drug lamotrigine (LTG) was recently shown to enhance IH in hippocampal CA1 pyramidal neurons, showing a potential anticonvulsant mechanism, as IH can dampen dendrito-somatic propagation of excitatory postsynaptic potentials in these cells. However, IH is also expressed in many hippocampal interneurons that provide synaptic inhibition to CA1 pyramidal neurons, and thus, IH modulation may indirectly regulate the inhibitory control of principal cells by direct modulation of interneuron activity. Whether IH in hippocampal interneurons is sensitive to modulation by LTG, and the manner by which this may affect the synaptic inhibition of pyramidal cells has not been investigated. In this study, we examined the effects of LTG on IH and spontaneous firing of area CA1 stratum oriens interneurons, as well as on spontaneous inhibitory postsynaptic currents in CA1 pyramidal neurons in immature rat brain slices. LTG (100 μM) significantly increased IH in the majority of interneurons, and depolarized interneurons from rest, promoting spontaneous firing. LTG also caused an increase in the frequency of spontaneous (but not miniature) IPSCs in pyramidal neurons without significantly altering amplitudes or rise and decay times. These data indicate that IH in CA1 interneurons can be increased by LTG, similarly to IH in pyramidal neurons, that IH enhancement increases interneuron excitability, and that these effects are associated with increased basal synaptic inhibition of CA1 pyramidal neurons.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 01/2010; 35(2):464-472. DOI:10.1038/npp.2009.150 · 7.05 Impact Factor
  • Russell M Sanchez · Jason A Justice · Kun Zhang ·
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    ABSTRACT: Hypoxia is the most common cause of neonatal seizures and can lead to epilepsy, but the epileptogenic mechanisms are not yet understood. We have previously shown that hypoxia-induced seizures in the neonatal rat result in acutely decreased amplitudes and frequency of spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) in hippocampal CA1 pyramidal neurons. In the current study, we asked whether such changes persist for several days following hypoxia-induced seizures. Similar to the acute findings, we observed decreased frequency and amplitudes of sIPSCs and decreased mIPSC amplitudes in CA1 pyramidal neurons at 3-5 days after hypoxia. However, in contrast to the acute findings, we observed no differences between hypoxia-treated and control groups in mIPSC frequency. Additionally, by 7 days after hypoxia, sIPSC amplitudes in the hypoxia group had recovered to control levels, but sIPSC frequency remained decreased. These data indicate that the persistently decreased sIPSC frequency result from decreased firing of presynaptic inhibitory interneurons, with only transient possible changes in postsynaptic responses to GABA release.
    Developmental Neuroscience 02/2007; 29(1-2):159-67. DOI:10.1159/000096220 · 2.70 Impact Factor