1. Chapter 17 Firing patterns of neurons
From Cellular and Molecular Neurophysiology, Fourth Edition.
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2. Figure 17.1 The inward rectification K+ current of medium spiny neurons.
(a) Membrane current (I) evoked by hyperpolarizing steps (V) to the indicated potentials (in mV), in control and in the presence of barium (10 μM). (b)I/V relations constructed from the steady-state I currents recorded in (a). Note the reversal potential at around −90 mV.
Adapted from Uchimura N, Cherubini E, North RA (1989) Inward rectification in rat nucleus accumbens neurons. J. Neurophysiol.62, 1280–1286, with permission.
From Cellular and Molecular Neurophysiology, Fourth Edition.
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3. 3 Figure 17.2 The long-latency discharge of medium spiny neurons.
(a) A suprathreshold current pulse is delivered in control conditions and in the presence of 4-AP. Between pulses, the cell membrane is hyperpolarized back to the original resting membrane potential (−80 mV). 4-AP decreases the first spike latency and increases the frequency of discharge. (b) Comparison of the voltage deflections produced by a sub-threshold 0.5 nA current pulse (400 ms duration) in the presence of TTX shows that 4-AP reduces the slope of the ramp potential and decreases the apparent time constant of the membrane (average of four responses).
Adapted from Nisenbaum ES, Xu ZC, Wilson CJ (1994) Contribution of a slowly inactivating potassium current to the transition to firing of neostriatal spiny projection neurons. J. Neurophysiol.71, 1174–1189, with permission.
From Cellular and Molecular Neurophysiology, Fourth Edition.
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4. 4 From Cellular and Molecular Neurophysiology, Fourth Edition.
Figure 17.3 Firing patterns of medium spiny neurons of the striatum according to the arousal state of the rat.
(Left column a–c)In vivo intracellular recording of the activity of spiny projection neurons of the striatum (bottom traces) together with the corresponding electroencephalogram (EEG) to check arousal state and electromyogram (EMG) to check spontaneous movements, during wakefulness (a), slow-wave sleep (b) and paradoxical sleep (c) in anesthetic free rats. (Middle column a–c) Expansion of the membrane fluctuations as indicated by the asterisk in the left columns (a), (b) nine superimposed traces, truncated records and (c) truncated record. (Right column a–c) Membrane potential distribution (bin size, 0.5 mV) calculated from the recording depicted in the left column. Recording is unimodal during wakefulness (a), is fitted by a double Gaussian (r2 = 0.97) during slow-wave sleep (b) and is unimodal but skewed toward more hyperpolarized potentials during paradoxical sleep.
Drawing by Jérôme Yelnik. Parts (a, b, c) from Mahon S, Vautrelle N, Pezard L, Slaght SJ, Deniau JM, Chouvet G, Charpier (2006) Distinct patterns of striatal medium spiny neuron activity during the natural sleep–wake cycle. J. Neurosci., 26, 12587–12595, with permission.
From Cellular and Molecular Neurophysiology, Fourth Edition.
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5. 5 From Cellular and Molecular Neurophysiology, Fourth Edition.
Figure 17.4 Complex spikes of inferior olivary neurons.
The activity of olivary neuron is intracellularly recorded under current clamp in cerebellar slices (inset represents five of these neurons). (a) Spontaneous low-frequency train of spikes from an olivary neuron, displayed at two different sweep speeds. The action potentials shown at left are displayed superimposed at right at a faster sweep speed. The first action potential which arises from the resting membrane potential level has a slightly higher amplitude at the peak and a rather prolonged plateau (after-spike depolarization, ADP) which is followed by an after-hyperpolarization. The rest of the spikes in the train become progressively shorter until failure of spike generation occurs (arrow, left) and the train terminates. (b) Effect of TTX (left) and Mn2+ (right) on the different parts of the complex spike evoked in two olivary neurons either by a depolarizing intracellular current pulse (left) or climbing fiber stimulation (CF, right).
Part (a) adapted from Llinas R, Yarom Y (1986) Oscillatory properties of guinea-pig inferior olivary neurones and their pharmacological modulation: an in vitro study. J. Physiol. (Lond.)376, 163–182, with permission. Part (b) adapted from Llinas R, Yarom Y. (1981) Electrophysiology of mammalian olivary neurones in vitro: different types of voltage-dependent ionic conductances. J. Physiol. (Lond.)315, 549–567, with permission. Drawing by Ramon Y Cajal, 1911.
From Cellular and Molecular Neurophysiology, Fourth Edition.
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6. Figure 17.5 The high- and low-threshold Ca2+ spikes of inferior olivary neurons.
Effect of membrane potential on excitability. A depolarizing current pulse of constant amplitude evokes (a, 1) a high-threshold Ca2+ spike (HTS) at resting membrane potential and (b, 1) a low-threshold Ca2+ spike (LTS) at a more hyperpolarized potential. Note that the ADP and AHP are smaller in (b) than in (a).
From left to right, effect of Co2+ and TTX in the same conditions. Adapted from Llinas R, Yarom Y (1981) Electrophysiology of mammalian olivary neurones in vitro: different types of voltage-dependent ionic conductances. J. Physiol. (Lond.)315, 549–567, with permission.
From Cellular and Molecular Neurophysiology, Fourth Edition.
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7. 7 From Cellular and Molecular Neurophysiology, Fourth Edition.
Figure 17.6 Ionic currents underlying the discharge configuration of inferior olivary neurons.
(a) In slightly depolarized cells, direct stimulation of the neuron by injecting a depolarizing current step evokes a sequence consisting of a TTX-sensitive action potential, followed by Ca2+-dependent events, a plateau (ADP), a period of after-hyperpolarization (AHP) and a depolarizing rebound of variable amplitude (four superimposed top traces). Schematic of this discharge configuration and indication of the different currents sequentially activated (see text for explanation) (bottom trace). (b) Direct intracellular injection of a hyperpolarizing current pulse is associated with a depolarizing sag and the generation of a rhythmic sequence of low-threshold Ca2+ spikes (top trace). Schematic of this discharge configuration and indication of the different currents sequentially activated (see text for explanation) (bottom trace). (c) Typical intracellular recording of the activity of an olivary neuron in vivo in an anesthetized rat. (Top trace) Sub-threshold oscillatory activity and epochs of suprathreshold activity. (Middle) The three marked areas in (c) top are shown at higher magnification. (Bottom) Superposition of the spikes from each epoch reveals the close association between the sub-threshold activity and the spikes. Note that in panel 3, two sub-threshold events are superimposed on the spike by aligning the peaks of sub-threshold events with the deflection point of the spike.
Part (a) adapted from Llinas R, Yarom Y (1981) Properties and distribution of ionic conductances generating electroresponsiveness of mammalian inferior olive neurons in vitro. J. Physiol. (Lond.)315, 569–584, with permission. Part (b) adapted from Bal T, McCormick D (1997) Synchronized oscillations in the inferior olive are controlled by the hyperpolarization-activated cation current Ih. J. Neurophysiol. 77, 3145–3156, with permission. Part (c) from Chorev E, Yarom Y, Lampl I (2007) Rhythmic episodes of subthreshold membrane potential oscillations in the rat inferior olive nuclei in vivo. J. Neurosci. 27, 5043–5052, with permission.
From Cellular and Molecular Neurophysiology, Fourth Edition.
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8. 8 From Cellular and Molecular Neurophysiology, Fourth Edition.
Figure 17.7 The intrinsic tonic firing of isolated Purkinje cells.
(a) Spontaneous action potentials recorded from an isolated Purkinje neuron in control conditions (left) and interspike interval histogram for the same cell (right). Dotted lines indicate −70 and 0 mV. (b) Spontaneous firing in control extracellular medium and in the presence of TTX as indicated. This cell continues to fire for some time in 10 nM of TTX (early) before silencing and resting at −51 mV (late). (c) Kinetics of Na+ currents evoked by the spike train protocol. The spike train in (a) is used as a command voltage (top trace) and the currents evoked are recorded in voltage clamp (bottom trace). The first 13 ms are shown. The arrow indicates the bump of Na+ current that occurs when the action potential command reaches its trough. Spike and bump Na+ currents are sensitive to TTX (not shown).
Adapted from Raman IM, Bean BP (1999) Ionic currents underlying spontaneous action potentials in isolated Purkinje neurons. J. Neurosci.19, 1663–1674, with permission.
From Cellular and Molecular Neurophysiology, Fourth Edition.
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9. Figure 17.8 Climbing fiber response of Purkinje cells and its after-effect.
(a) All-or-none dendritic (d, top) and somatic (s, bottom) climbing fiber response. The position of the traces relative to the drawing of the recorded Purkinje cell indicates the recording sites. (b) Climbing fiber (CF) response followed by a transient inactivation of spontaneous firing. (c) Climbing fiber stimulation at 1 Hz (arrowheads). (d) At a slower sweep speed, the long-lasting hyperpolarization following a train of climbing fiber stimulation at 1 Hz is shown.
Adapted from Hounsgaard J, Mitgaard J (1989) Synaptic control of excitability in turtle cerebellar Purkinje cells. J. Physiol. (Lond.)409, 157–170, with permission.
From Cellular and Molecular Neurophysiology, Fourth Edition.
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10. Figure 17.9 Integration of Na+ and Ca2+ action potentials in Purkinje cells.
The activity of Purkinje cells is recorded intracellularly in the soma and in three different regions of the dendritic tree (current clamp mode) in cerebellar slices. Na+-dependent action potentials are spontaneously evoked at the soma–axon hillock region. They passively backpropagate in the dendritic tree (note their rapid and strong diminution in amplitude). Ca2+-dependent action potentials evoked at different points of the dendritic tree (in response to climbing fiber activation) propagate passively to the axon hillock region where they evoke the complex response followed by a period of cell silence.
Adapted from Llinas R, Sugimori M (1980) Electrophysiological properties of in vitro Purkinje cell dendrites in mammalian cerebellar slices. J. Physiol. (Lond.)305, 197–213, with permission.
From Cellular and Molecular Neurophysiology, Fourth Edition.
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11. Figure 17.10 The two states of activity of thalamic and subthalamic neurons.
(a) The activity of a thalamocortical neuron (inset) is recorded in current clamp. When depolarized to −58 mV with intracellular injection of current, the neuron displays the tonic firing mode and switches to the oscillatory bursting mode when hyperpolarized. (b) The same protocol applied to a subthalamic neuron (inset) allows one to record the two firing modes. When the membrane is further hyperpolarized, the cell becomes silent.
Part (a) adapted from McCormick DA, Pape HC (1990) Properties of a hyperpolarization-activated cation current and its role in rhythmic oscillation in thalamic relay neurons. J. Physiol. (Lond.)431, 291–318, with permission. Part (b) adapted from Beurrier C, Congar P, Bioulac B, Hammond C (1999) Subthalamic neurons switch from single-spike activity to burst-firing mode. J. Neurosci.19, 599–609, with permission. Drawings by Jérôme Yelnik.
From Cellular and Molecular Neurophysiology, Fourth Edition.
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12. Figure 17.11 Na+ currents are critical for intrinsic tonic firing mode of subthalamic neurons.
(a) Tonic activity of an STN neuron recorded in control medium and during application of Co2+ (left). Right traces show that the low-threshold Ca2+ spike evoked at the break of a hyperpolarization pulse is strongly decreased in Co2+ to attest that Ca2+ channels are effectively blocked in these conditions. (b) Tonic activity recorded in control medium and at the onset of TTX (1 μM) application. (c) Persistent Na+ current recorded in whole-cell patch clamp in response to a depolarizing ramp (5 mV s−1) in the absence (control) and presence of TTX.
Parts (a) and (c) adapted from Beurrier C, Bioulac B, Hammond C (2000) Slowly inactivating sodium current (INaP) underlies single-spike activity in rat subthalamic nucleus. J. Neurophysiol. 83, 1951–1957, with permission. Part (b) adapted from Bevan MD, Wilson CJ (1999) Mechanisms underlying spontaneous oscillation and rhythmic firing in rat subthalamic neurons. J. Neurosci. 19, 7617–7628, with permission.
From Cellular and Molecular Neurophysiology, Fourth Edition.
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13. Figure 17.12 Thalamic oscillations depend on a low-threshold Ca2+ spike (LTS).
When the membrane of a thalamocortical neuron is hyperpolarized to −65 mV, a depolarizing current pulse evokes an LTS that is insensitive to TTX and abolished by Co2+ (1 mM). Note the presence of a TTX-sensitive Na+ spike in control conditions.
Adapted from Llinas R, Jahnsen H (1982) Electrophysiology of thalamic neurons in vitro. Nature297, 406–408, with permission.
From Cellular and Molecular Neurophysiology, Fourth Edition.
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14. Figure 17.13 Contribution of Ih to resting potential and firing mode.
(a) Thalamocortical neuron. A depolarizing current pulse from resting potential (−72 mV) which does not result in an LTS (1) or the generation of action potential is applied. Cs application results in a substantial hyperpolarization of the membrane that de-inactivates the LTS thereby activating a burst of spikes (2). Compensation for the hyperpolarization with intracellular injection of current (+ DC) reveals that the AHP is nearly abolished during Cs+ (3). (b) Subthalamic (STN) neuron. In control conditions, at rest, an STN neuron discharges in the single-spike mode. Bath application of Cs+ hyperpolarizes the membrane by 8 mV and shifts STN activity to burst firing mode. Continuous injection of positive current shifts the membrane potential back to the control value and to single-spike activity, though Cs+ is still present. Concomitantly, the depolarizing sag in response to negative current pulse is strongly decreased as well as the depolarizing rebound seen at the break of pulse, to attest that Ih is strongly reduced (insets).
Part (a) adapted from McCormick DA, Pape HC (1990) Properties of a hyperpolarization-activated cation current and its role in rhythmic oscillation in thalamic relay neurons. J. Physiol. (Lond.)431, 291–318, with permission. Part (b) adapted from Beurrier C, Bioulac B, Hammond C (2000) Slowly inactivating sodium current (INaP) underlies single-spike activity in rat subthalamic nucleus. J. Neurophysiol. 83, 1951–1957, with permission.
From Cellular and Molecular Neurophysiology, Fourth Edition.
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15. 15 Figure 17.14 Currents underlying the tonic and burst firing modes.
Recordings and scheme of the ionic basis of (a) the tonic mode and (b) the bursting mode of thalamic neurons.
Adapted from McCormick DA, Pape HC (1990) Properties of a hyperpolarization-activated cation current and its role in rhythmic oscillation in thalamic relay neurons. J. Physiol. (Lond.)431, 291–318; and Bal T, McCormick DA (1993) Ionic mechanisms of rhythmic burst firing and tonic activity in the nucleus reticularis thalami, a mammalian pacemaker. J. Physiol. (Lond.)468, 669–691, with permission.
From Cellular and Molecular Neurophysiology, Fourth Edition.
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16. Figure In vivo, thalamic neurons display the single-spike or bursting mode, in relation to behavioral state.
Simultaneous display of (a) eye movements (electro-oculogram, EOG) and (b) membrane potential of an intracellularly recorded thalamic neuron during slow-wave sleep (S sleep) and paradoxical sleep (P sleep) in an intact animal. (b) The neuron is already depolarized by 8 mV, when the animal enters P sleep (first eye movement, arrow). Depolarization is maintained throughout P sleep. Upon last eye movement (double arrow), membrane potential repolarizes as the animal goes back to S sleep (the trace is filtered at 0–75 Hz). (c) Enlarged sequences (labeled 1 and 2 under trace (b)) of spontaneous activities: 1, bursting mode during S sleep (hyperpolarized resting potential); 2, single-spike mode during P sleep (depolarized resting potential).
Adapted from Hirsch J, Fourment A, Marc ME (1983) Sleep-related variations of membrane potential in the lateral geniculate body relay neurons of the cat. Brain Res. 259, 308–312, with permission.
From Cellular and Molecular Neurophysiology, Fourth Edition.
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