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ARTICLE, Behavioral/Systems

Reduced Inhibition in an Animal Model of Cortical Dysplasia

Wei Jian Zhu and Steven N. Roper
Journal of Neuroscience 1 December 2000, 20 (23) 8925-8931
Wei Jian Zhu
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Steven N. Roper
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  • Fig. 1.
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    Fig. 1.

    Morphological and physiological properties of a pyramidal neuron in dysplastic cortex. A, Composite videomicrograph of a representative biocytin-filled pyramidal cell with the soma lying in the center of the dysplastic cortex, dendrites extending to the pial surface (top), and the axon extending into the white matter. Scale bar, 100 μm. B, Photomicrograph of a cresyl violet-stained section of dysplastic cortex (40 μm thick) demonstrating thinning of the cortex, loss of laminar organization, and loss of orientation of pyramidal cells (pial surface is at top) Scale bar, 100 μm. C, Current-clamp recording (top trace) of a pyramidal neuron from dysplastic cortex demonstrating the response to depolarizing current (bottom trace). Elicited action potentials show frequency adaptation that is indicative of a regular spiking neuron.

  • Fig. 2.
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    Fig. 2.

    Decreased amplitude and frequency of sIPSCs from pyramidal neurons in dysplastic cortex. A, Representative traces of voltage-clamp recordings from pyramidal neurons in control neocortex and dysplastic cortex in the presence of AP-5 (50 μm) and CNQX (10 μm). B, C, Group comparison of amplitude and frequency of sIPSCs and mIPSCs from pyramidal neurons in control neocortex and DC. Graphs show data for amplitude (B) and frequency (C) of sIPSCs (left) and mIPSCs (right). B, Mean values of sIPSC amplitude were decreased in DC (p < 0.001), but the mIPSC amplitude was not different (p= 0.83). C, Mean frequencies of both sIPSCs and mIPSCs were significantly reduced in DC (p < 0.001 for both measures).

  • Fig. 3.
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    Fig. 3.

    Decreased frequency of mIPSCs in pyramidal neurons from dysplastic cortex. A, Representative voltage-clamp recordings of mIPSCs from pyramidal neurons from control and dysplastic cortex in the presence of AP-5 (50 μm), CNQX (10 μm), and TTX (1 μm). B, Distribution histograms of mIPSC amplitude from these cells show similar patterns. Normalized cumulative probability curves show no difference between control and dysplastic cortex for mIPSC amplitude (C; p = 0.16), but the interevent interval (D) is shifted to the right (consistent with decreased frequency) in the neuron from dysplastic cortex (p < 0.0001).

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    Fig. 4.

    Monosynaptic evoked IPSCs recorded from pyramidal neurons from control and dysplastic cortex in the presence of AP-5 (50 μm) and CNQX (10 μm). A, Representative recordings of monosynaptic eIPSCs show a smaller response in the neuron from dysplastic cortex (bottom trace) compared with the control neuron (top trace). B, Group comparison of data from control and dysplastic cortex shows a significant reduction in monosynaptic eIPSC amplitude in pyramidal neurons from dysplastic cortex (p < 0.002).

  • Fig. 5.
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    Fig. 5.

    Evoked EPSCs recorded at the reversal potential of GABAgeric currents in pyramidal neurons from control and dysplastic cortex. A, Representative recordings of eEPSCs in pyramidal neurons from control and dysplastic cortex. Evoked EPSCs from dysplastic cortex typically demonstrated a complex response comprising multiple inward currents. B, Group comparison of data from control and dysplastic cortex shows an increase in eEPSC peak amplitude in dysplastic cortex (p < 0.001).C, The averaged area of eEPSCs in dysplastic cortex was also significantly increased (p < 0.001).

  • Fig. 6.
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    Fig. 6.

    Paired pulse modulation of evoked EPSCs recorded from pyramidal neurons in control and dysplastic cortex with an interpulse interval of 20 msec. A, Representative recordings of paired eEPSCs in pyramidal cells from control and dysplastic cortex show that the amplitude of the second response was reduced in the control neuron but increased in the neuron from dysplastic cortex. B, Group data from control and dysplastic cortex demonstrate an absence of paired pulse depression in dysplastic cortex (p < 0.001).

  • Fig. 7.
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    Fig. 7.

    Increased amplitude and frequency in sEPSCs in pyramidal neurons from control and dysplastic cortex. A, Representative voltage-clamp recordings demonstrate a significant increase in amplitude and frequency of sEPSCs in the pyramidal neuron from dysplastic cortex compared with the control neuron.B, Amplitude distribution histograms of sEPSCs from pyramidal neurons from control and dysplastic cortex show that sEPSCs were skewed toward larger amplitudes, especially in dysplastic cortex.C, Normalized cumulative probability curves of sEPSC amplitude show that values from the dysplastic cortex neuron were significantly shifted to the right (p < 0.0001), indicating an increase in sEPSC amplitude in this cell.D, Normalized cumulative probability curves of interevent intervals are significantly shifted to the left in the pyramidal neuron from dysplastic cortex compared with the control neuron (p < 0.0001), indicating an increase in sEPSC frequency in the dysplastic cortex neuron.

  • Fig. 8.
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    Fig. 8.

    Group comparisons of amplitude and frequency of sEPSCs and mEPSCs from pyramidal neurons from control and dysplastic cortex. Graphs show data for amplitude (A) and frequency (B) of sEPSCs (left) and mEPSCs (right). Mean values of sEPSC amplitude were increased in dysplastic cortex (p < 0.001), but there was no difference in mean mEPSC amplitude between the two groups (p = 0.21). Mean sEPSC frequency was increased in dysplastic cortex (p < 0.001), but there was no difference in mean frequency of mEPSCs between the two groups (p = 0.67).

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    Table 1.

    Membrane properties and postsynaptic currents in the pyramidal neurons of cortex

    Control pyramidal neuronDC pyramidal neuron
    Layer II/IIILayer V
    Membrane properties
     Vm (mV)−67.2  ± 2.8−69.6  ± 3.1−68.5  ± 2.6
     Ra(mΩ)16.3  ± 1.215.9  ± 1.514.7  ± 1.8
     Rm (mΩ)203  ± 15222  ± 18211  ± 20
     n  14  10 22
    sIPSCs
     Amp (pA)33.88  ± 1.3934.51  ± 1.222.4  ± 1.77*
     Fre (Hz)13.19  ± 0.8813.73  ± 0.944.07  ± 0.46*
     RT (msec)1.85  ± 0.171.63  ± 0.181.88  ± 0.11
     τ (msec)10.64  ± 0.8111.36  ± 0.9811.4  ± 0.82
     n  11 9  19
    sEPSCs
     Amp (pA)22.94  ± 1.0221.78  ± 1.0228.8  ± 0.92*
     Fre (Hz)2.84  ± 0.293.11  ± 0.285.49  ± 0.47*
     RT (msec)1.91  ± 0.111.77  ± 0.162.02  ± 0.16
     τ (msec)8.00  ± 0.437.82  ± 0.687.38  ± 0.7
     n  14  11  28
    • DC, Dysplastic cortex; Vm, resting membrane potential; Ra, access resistance; Rm, membrane resistance; Amp, amplitude; Fre, frequency; RT, 10–90% rise time; τ, decay time constant.

    • ↵* p < 0.001.

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The Journal of Neuroscience: 20 (23)
Journal of Neuroscience
Vol. 20, Issue 23
1 Dec 2000
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Reduced Inhibition in an Animal Model of Cortical Dysplasia
Wei Jian Zhu, Steven N. Roper
Journal of Neuroscience 1 December 2000, 20 (23) 8925-8931

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Reduced Inhibition in an Animal Model of Cortical Dysplasia
Wei Jian Zhu, Steven N. Roper
Journal of Neuroscience 1 December 2000, 20 (23) 8925-8931
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