1. Chapter 15 Somato-dendritic processing of postsynaptic potentials Ii
Chapter 15 Somato-dendritic processing of postsynaptic potentials Ii. Role of sub-threshold depolarizing voltage-gated currents
From Cellular and Molecular Neurophysiology, Fourth Edition.
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2. Figure 15.1 Synaptic integration in CA1 pyramidal neurons is independent of location.
Upper traces: The average unitary excitatory postsynaptic potentials (EPSPs) recorded at the soma of a neuron receiving distal and proximal input. Somatic EPSP amplitude is similar in spite of location differences. Lower traces: The amount of temporal summation at the soma is the same for a 50 Hz train of stimuli applied to distal (300 μm) or to proximal Schaffer collateral inputs (50 μm). (b) A CA1 pyramidal neuron showing the location of proximal and distal synaptic inputs across the dendritic arbor.
Adapted from Magee JC (2000) Dendritic integration of excitatory synaptic input. Nat. Neurosci. Rev.1, 181–190, with permission.
From Cellular and Molecular Neurophysiology, Fourth Edition.
Copyright © 2015 Elsevier Ltd. All rights reserved.

3. Figure 15.2 Persistent Na+ channel activity in dendrites of cortical pyramidal neurons.
(a) Na+-channel currents evoked by a 50 ms depolarizing pulse. The current traces shown are consecutive sweeps (scale bar 2 pA and 5 ms). Insets: Ensemble average current obtained from 20 consecutive sweeps (scale bar 2.5 pA and 5 ms). (b) Voltage dependence of the persistent component of ensemble average currents obtained as in (a). The plot is normalized to the absolute value of its peak amplitude.
Adapted from Magistretti J, Ragsdale DS, Alonso A (1999) Direct demonstration of persistent Na+ channel activity in dendritic processes of mammalian cortical neurones. J. Physiol. (Lond.)521, 629–636, with permission.
From Cellular and Molecular Neurophysiology, Fourth Edition.
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4. Figure 15.3 INaP activation and the resultant SBFI fluorescence changes in the soma of a pyramidal neuron of the neocortex.
(a) Intracellular recording (voltage clamp mode) of the current evoked by a depolarizing ramp from −72 mV to a 1 s constant step at −50 mV (top traces). The corresponding decrease of SBFI fluorescence in the soma is shown in the bottom trace. The arrow indicates time of voltage clamp. A decrease of SBFI fluorescence reflects an increase of intracellular Na+ concentration. (b) The same experiment in the presence of 1 μM of TTX in the bath.
Adapted from Mittman T, Linton SM, Schwindt P, Crill W (1997) Evidence of persistent Na+ current in apical dendrites of rat neocortical neurons from imaging of Na+-sensitive dye. J. Neurophysiol.78, 1188–1192, with permission.
From Cellular and Molecular Neurophysiology, Fourth Edition.
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5. 5 From Cellular and Molecular Neurophysiology, Fourth Edition.
Figure 15.4 INaP is predominantly expressed in the axons of layer V neocortical pyramidal neurons.
(a) Schematic depicting the effect of local dendritic application of TTX on the amplitude of the persistent sodium current (INaP) in layer V neocortical pyramidal neurons. INaP is measured in response to a voltage ramp using whole-cell somatic voltage-clamp recordings. Local application of TTX on the apical dendrite does not modify the amplitude of INaP. (b) Same experiment as in (a) showing the lack of effect of local somatic application of TTX on INaP. (c) In contrast to dendritic (a) and somatic (b) applications, local application of TTX on the axon strongly reduces the amplitude of INaP (top traces). (d) Scatter plot showing the percentage of inhibition of INaP by TTX as a function of the location of the TTX application. While axonal applications (left, negative distances from the soma) strongly reduce INaP amplitude, somatic (0 μm) and dendritic (positive distances from the soma) have negligible effects on INaP amplitude.
Adapted from Astman N, Gutnick MJ, Fleidervish IA (2006), Persistent sodium current in layer 5 neocortical neurons is primarily generated in the proximal axon. J. Neurosci.26, 3465–3473.
From Cellular and Molecular Neurophysiology, Fourth Edition.
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6. Figure 15.5 Dendritic low-voltage-activated Ca2+ channel activity in pyramidal neurons of the hippocampus.
(a) Consecutive sweeps of T-type Ca2+-channel activity recorded from a dendrite-attached patch (voltage clamp mode) in response to 60 ms depolarizing steps to −15 mV (VH = −85 mV). Bottom trace is the ensemble average (104 sweeps) demonstrating significant inactivation during the 60 ms depolarizing step (110 mM of Ba2+ in the recording solution). (b)iT/V plot of T-type Ca2+-channel activity. Unitary current amplitude is plotted as a function of membrane potential for patches recorded with either 20 mM (•) or 110 mM (ˆ) Ba2+ as charge carrier. The slope (unitary conductance) γT is between 7 pS (20 mM of Ba2+) and 11 pS (110 mM of Ba2+). (c) Representative steady-state activation (j) and inactivation (m) plots for dendritic LVA Ca2+ channels recorded in 20 mM of Ba2+.
Adapted from Magee JC, Johnston D (1995) Characterization of single voltage-gated Na+ and Ca2+ channels in apical dendrites of rat CA1 pyramidal neurons. J. Physiol. (Lond.)487, 67–90, with permission.
From Cellular and Molecular Neurophysiology, Fourth Edition.
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7. Figure 15.6 Synaptic activation of LVA Ca2+ channels in hippocampal CA1 pyramidal neurons.
Sub-threshold EPSPs are evoked by Schaffer collateral stimulation and are recorded from the soma (in current clamp mode) after propagation in the dendritic tree. (a) Consecutive sweeps of dendrite-attached recordings (voltage clamp mode) with the patch held at −65 mV showing Ca2+-channel activity recorded at the dendritic site (i, top traces) and of sub-threshold EPSPs (v, bottom traces) recorded at the somatic site (whole-cell configuration). (b) Hyperpolarizing prepulses (not shown) increase the activation of T-type Ca2+ channels by an EPSP. Ensemble average of 50 consecutive current traces without prepulse (2), ensemble average of 60 consecutive current traces after a 4 s prepulse of −20 mV (3), and ensemble average of 60 consecutive traces after a 4 s prepulse of −40 mV (4). The patch is returned to a holding potential that is 10 mV depolarized from resting potential 400 ms before synaptic stimulation in order to evoke an EPSP of similar amplitude (1) in all trials.
Adapted from Magee JC, Johnston D (1995) Synaptic activation of voltage-gated channels in the dendrites of hippocampal pyramidal neurons. Science268, 301–304, with permission.
From Cellular and Molecular Neurophysiology, Fourth Edition.
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8. Figure 15.7 Sub-threshold EPSPs cause a localized, Ni2+-sensitive elevation of intradendritic Ca2+ concentration.
Sub-threshold EPSPs are evoked by stimulation of afferents close to the dendrite under study. (a) Time course of percentage change in FURA-2 fluorescence in a dendrite (%ΔF/F, top trace) evoked by a short train of five EPSPs and somatic voltage recordings (V) of the five EPSPs (whole-cell configuration, current clamp mode, bottom trace). The fluorescence trace is from the region delimited by the small black frame on the schematic representation of the FURA-2 loaded neuron. (b) Localized percent change in FURA-2 fluorescence (%ΔF/F, top trace) induced by a short train of five EPSPs and somatic voltage recordings of the five EPSPs (bottom traces) in the absence (1), presence (2) and 20 min after washing (3) of 50 μM of NiCl2. The somatic recording of EPSPs (bottom traces) is unaffected by Ni2+ application. All traces in the figure are averages of five consecutive sweeps.
Adapted from Magee JC, Christofi G, Miyakawa H et al. (1995) Subthreshold synaptic activation of voltage-gated Ca2+ channels mediates a localized Ca2+ influx into the dendrites of hippocampal pyramidal neurons. J. Neurophysiol.74, 1335–1342, with permission.
From Cellular and Molecular Neurophysiology, Fourth Edition.
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9. Figure 15.8 EPSPs in hippocampal pyramidal dendrites are amplified by an amiloride- and Ni2+-sensitive Ca2+ current.
EPSPs are evoked by stimulation of afferent fibers in the outer stratum radiatum. EPSPs are recorded from the soma (whole-cell configuration, current clamp mode) at two different membrane potentials (−70 and −90 mV) adjusted by current injection through the whole-cell pipette. Superimposed traces of averaged EPSPs (n = 50) recorded before and during local dendritic application of amiloride (50 μM, left) or Ni2+ (5 μM, right) show that both drugs reduce EPSPs recorded at −70 mV but do not significantly reduce them at −90 mV.
Adapted from Gillessen T, Alzheimer C (1997) Amplification of EPSPs by low Ni2+ and amiloride-sensitive Ca2+ channels in apical dendrites of rat CA1 pyramidal neurons. J. Neurophysiol. 77, 1639–1643, with permission.
From Cellular and Molecular Neurophysiology, Fourth Edition.
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10. Figure 15.9 Dendritic and somatic hyperpolarization-activated cation current Ih in pyramidal neurons of the hippocampus.
(a) In a dendrite-attached macropatch located in the apical dendrite (310 μm from the soma), hyperpolarizing steps to −125 mV (VH = −45 mV) evoke inward currents that are larger than those recorded from the soma with similar-sized pipettes. (b)I/V plots for steady-state inward current measured 900 ms after the start of the step (▲) and for inward tail current measured 5 ms after the end of the step (•). (c) Blockade by 5 mM of external Cs+ of the inward current evoked by a hyperpolarizing step to −140 mV. (d) Activation curves generated from the tail currents (inset). The dendritic curve (V1/2 = −89 mV) is shifted 6 mV hyperpolarized with respect to the somatic curve (V1/2 = −83 mV). Command potentials (Vstep) are given in 10 mV increments from −65 to −135 mV.
Adapted from Magee JC (1998) Dendritic hyperpolarization-activated currents modify the integrative properties of hippocampal CA1 pyramidal neurons. J. Neurosci.18, 7613–7624, with permission.
From Cellular and Molecular Neurophysiology, Fourth Edition.
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11. 11 Figure 15.10 Ih is situated on the distal apical dendrite.
(a) Consecutive cell-attached patches along the apical dendrite of a layer V pyramidal neuron at different distances from the soma using a high-K+ pipette solution. Hyperpolarizing voltage commands to approximately −125 mV resulted in the activation of tiny Ih currents at distances smaller than 400 μm from the soma, while at more distal recording sites a large Ih current flow could be induced. After the cell-attached recordings, the cell was filled with biocytin by going to whole-cell mode and the resting membrane potential measured. (b) The Ih current densities from 60 cell-attached recordings were plotted against their distance from the soma. While on the basal dendrites, the soma, and the apical dendrite <400 μm nearly no Ih currents could be found, more distal recordings <820 μm showed a marked non-linear increase in Ih density.
Adapted from Berger T, Larkum ME, Luscher HR (2001) High Ih channel density in the distal apical dendrite of layer V pyramidal cells increases bidirectional attenuation of EPSPs. J. Neurophysiol.85, 855–868, with permission.
From Cellular and Molecular Neurophysiology, Fourth Edition.
Copyright © 2015 Elsevier Ltd. All rights reserved. 11

12. Figure EPSP amplitude, duration and summation are all regulated by Ih in hippocampal pyramidal neurons.
EPSPs are generated by injection of an exponentially rising and falling voltage waveform into the current clamp input of the amplifier (dendritic current injections are performed 250 μm away from the soma). Simultaneous whole-cell recordings are performed from the dendrite and the soma of the same pyramidal neuron. (a) A single current injection into the dendritic electrode produces an EPSP-shaped transient, the amplitude and duration of which is increased in the presence of 3 mM of external Cs+. (b) Repetitive current injections produce a train of EPSP-shaped voltage transients, the peak amplitude and duration of which are also increased in the presence of 3 mM of external Cs+.
Adapted from Magee JC (1998) Dendritic hyperpolarization-activated currents modify the integrative properties of hippocampal CA1 pyramidal neurons. J. Neurosci. 18, 7613–7624, with permission.
From Cellular and Molecular Neurophysiology, Fourth Edition.
Copyright © 2015 Elsevier Ltd. All rights reserved. 12

13. Figure 15.12 IA is strongly expressed in hippocampal pyramidal dendrites and attenuates EPSPs.
(a) Left, schematic depicting the experiment design: cell-attached voltage-clamp recordings of potassium currents were performed at the somatic (blue electrode) and dendritic (red electrode) levels. Right, scatter plot showing the distribution of amplitudes of the transient and sustained potassium currents in hippocampal pyramidal dendrites as a function of the recording distance from the soma. While the transient component (IA, filled circles) shows a strong increase in expression between the soma (blue circles) and the distal dendrite (red circles), the sustained component shows a stable amplitude along the entire dendrite. (b) Simultaneous dendritic (top traces) and somatic (bottom traces) voltage-clamp recordings illustrating the differences in the distribution of the transient and sustained currents that can be observed in a hippocampal pyramidal neuron. Red traces correspond to distal dendritic recordings and blue traces to somatic recordings (same as in panel (a)). (c) Effect of the pharmacological blockade of IA on the integration of simulated dendritic EPSPs. EPSPs recorded in the soma in response to dendritic current injection are amplified when IA is blocked using 4-AP (red trace). Although this effect involves the TTX-sensitive sodium current, the effect of 4-AP persists in the presence of TTX, demonstrating that IA blockade on its own has an effect on the dendritic integration of EPSPs. The amplification revealed in 4-AP demonstrates that IA attenuates EPSPs in control conditions.
Adapted from Hoffman DA, Magee JC, Colbert CM, Johnston D (1997) K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons. Nature 387, 869–875, with permission.
From Cellular and Molecular Neurophysiology, Fourth Edition.
Copyright © 2015 Elsevier Ltd. All rights reserved. 13