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Intrinsic Electrical Properties of Mammalian Neurons and CNS Function: A Historical Perspective

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Review

Intrinsic Electrical Properties of Mammalian Neurons and CNS Function: A Historical Perspective

Rodolfo R Llinás. Front Cell Neurosci.

Abstract

This brief review summarizes work done in mammalian neuroscience concerning the intrinsic electrophysiological properties of four neuronal types; Cerebellar Purkinje cells, inferior olivary cells, thalamic cells, and some cortical interneurons. It is a personal perspective addressing an interesting time in neuroscience when the reflex view of brain function, as the paradigm to understand global neuroscience, began to be modified toward one in which sensory input modulates rather than dictates brain function. The perspective of the paper is not a comprehensive description of the intrinsic electrical properties of all nerve cells but rather addresses a set of cell types that provide indicative examples of mechanisms that modulate brain function.

Keywords: mammalian neurons; oscillations; oscillatory phase reset; oscillatory resonance; voltage-gated ion channels.

Figures

Figure 1
Figure 1
Simultaneous intracellular recording from Guinea pig cerebellar Purkinje cell dendrite and soma in vitro. (A) Diagram of intracellular recording sites at somatic and dendritic levels and the location of the extracellular glutamic acid iontophoretic application site. (B) Intradendritic recording. The large amplitude wide action potentials are Ca-dependent while the smaller fast action potentials represent the passive invasion of the somatic action potentials into the dendritic tree. Note the presence of a sustained plateau depolarization at the dendritic level following the spiking phase of the dendritic response. (C) Simultaneous intrasomatic recording showing fast somatic Na-dependent action potentials. Note that each of the large somatic spikes is seen at dendritic level with a short delay and that the calcium dependent dendritic spikes generate high frequency spiking as somatic level. (D) Superposition of dendritic (red) and somatic (blue) spikes to illustrate the temporal relationship between somatic and dendritic spikes and plateau amplitudes (Llinás and Sugimori, ,. This example is unpublished).
Figure 2
Figure 2
Ionic basis for Purkinje somatic recordings. (A) Activity elicited from Purkinje cell soma by direct depolarization. Note fast spikes and underlying slower depolarizations. (B) After blocking the calcium conductance by addition of Co to the bath direct depolarization elicited fast spikes. Note that with increased depolarization spike onset moved to the left (arrows), but the plateau level of spike threshold did not change. (C) Repetitive response to somatic depolarization. (D) Block of sodium channels with TTX reveals underlying slow spikes and afterdepolarization (arrow). (From Llinás and Sugimori, .).
Figure 3
Figure 3
High-resolution fluorescent image of a dendritic calcium spike in a Purkinje cell filled with fura-2 by microinjection (380-nm excitation). (From Tank et al., .).
Figure 4
Figure 4
Multiple conductance of Ca2+ channels in the somata and dendrites of cerebellar Purkinje cells. (A) Single Ca2+ channel currents carried by 110 mM Ba2+ in a somatic patch, evoked by voltage step jumps (≈70 ms) applied once every 5 s. Three opening levels are indicated by solid, dashed, and dotted lines. (B) Currents in a dendritic patch. Same conditions as in (A). Voltage dependence (C,D) for the currents levels illustrated in (A,B). Pooled data for 8 somatic and 5 dendritic patches. The indicated conductances are the slope of the lines through the dots (from Usowicz et al., 1992).
Figure 5
Figure 5
Ionic conductances and the mechanism for oscillation in inferior olivary cells. Left: Drawing of an inferior olivary cell by Ramón y Cajal. Center: Table giving the distribution of ionic conductances in somatic and dendritic regions. At the soma a set of conductances (gNa and gk) generating fast action potentials may be observed. In addition, a strongly inactivated Ca2+ conductance is present, which produces rebound spikes, as seen in (B) [gCa (somatic)]. Also recorded at the soma is a large Ca2+-dependent dendritic spike [gCa (dendtritic)] that generates the afterdepolarization and the powerful, long-lasting afterhypolarization, which is produced by a Ca2+-dependent K+ conductance [gK(Ca)]. In addition, a voltage-dependent K+ conductance (gK) seems to be present in the dendrites. Right A: Rebound spikes in the inferior olivary neuron (arrow) following blockage of the Na spike with tetrodotoxin (TTX). Right B: Summary of the ionic conductances that generate single-cell oscillations in neurons of the inferior olive.
Figure 6
Figure 6
Inward current in inferior olive cell after block of sodium and potassium currents with TTX and TEA, respectively. (A) A set of transmembrane square voltage camp steps of increasing amplitude generated a rapidly inactivating, transient, Ca current (Ica). (B) This current is blocked by addition of octanol. (C) Plot of the current voltage relation in (A). (From Llinás and Yarom in Llinás et al., 1989).
Figure 7
Figure 7
Spontaneous bursts of spikes recorded intracellularly from an IO neuron displayed at different sweep speeds. (A) The neuron fired four action potentials and a fifth subthreshold response that corresponds to a subthreshold somatic Ca2+-dependent spike. (B) A longer burst of spikes is shown at a slower sweep speed. Note that the first interspike interval in the burst was longer than the rest. (C) The rising phase of the action potentials in (B) are superimposed to illustrate the change in after-depolarization duration during the train. Note that the first action potential (which arises from the resting membrane potential level) has the longest after-depolarization. The other spikes in the train became progressively shorter until failure of spike generation occurred and the burst terminated. (D) The same set of records as in (B), showing the duration of the after-hyperpolarization and the rebound somatic Ca2+-dependent spikes. (Modified from Llinás and Yarom, 1986).
Figure 8
Figure 8
IO oscillatory properties following spike activation. (A) One extracellular stimulus briefly interrupted the spontaneous oscillation. (B) Superimposition of six traces demonstrating the reset oscillatory phase is the same regardless at which point of the intrinsic oscillation the stimulus was delivered. Inset, power spectra for traces. (Leznik et al., 2002). (C) Lissageu figure obtained from the analysis of an IO neuron oscillation. The regularity of the figure shows that the IO attractor has a regular, periodic trajectory. (D) Calculated Lyapunov exponents indicative of low-dimensional chaotic dynamics.
Figure 9
Figure 9
Electrophysiological properties of thalamic cells recorded in vitro. (A,B) Depolarizing current pulses (bottom traces) elicited no response when delivered from the resting potential, tonic firing when delivered from a depolarized potential (A) and a burst response when delivered from a hyperpolarized level (B). (C) Rebound response seen after hyperpolarizing pulses. (D,E) Calcium currents elicited by membrane depolarization from a hyperpolarized potential (D) and current–voltage relationship (E). (Geijo-Barrientos and Llinás, unpublished observations).
Figure 10
Figure 10
The spike generation properties and EPSP amplitude generated by a thalamic neurons to cortico-thalamic volleys is membrane potential depend. (A) At −70 mV the thalamic cell generated spikes at frequencies bellow 10 Hz. Note that the EPSPs generated are all of the same amplitude (bottom trace). (B) At a resting potential of −56 mV the EPSP amplitude for the same cortical volley was initially smaller, but increased in amplitude with stimulus frequency. It could follow high frequency stimulation and produce rapid neuronal spike firing. (From Pedroarena and Llinás, .).
Figure 11
Figure 11
Generation of gamma band oscillation by thalamic dendrites. (A) Three different levels of membrane potential are accompanied by a rapid membrane potential oscillation with clear gamma band frequency at −46 and −43 mV. This is demonstrated by the dominant frequency at 37.5 Hz at −43 mV as shown in the auto-correlogram (insert). (B) At a membrane potential of −40 mV action potentials were generated at the peak of each oscillatory wavelet and so the subthreshold oscillatory membrane properties are transformed into gamma band spike frequency projected via thalamocortical axons on to the cortical mantle. (C,D) The mechanism for this gamma band oscillation was of dendritic origin was tested with a computer model. (E) Direct demonstration that the gamma oscillations are mostly dendritic and carried by calcium ions was accomplished using calcium specific fura 2 fluorescence imaging. The cell was depolarized to the level that elicited fast firing calcium entry was restricted to the dendritic tree (yellow and red) (F). Diagram of the oscillatory properties of thalamic neurons and the recurrent inhibition at somatic level via the thalamic nucleus reticular nucleus. [(A,B,E,F) from Pedroarena and Llinás, ; (C,D) from Rhodes and Llinás, .].
Figure 12
Figure 12
Conducances underlying the oscillatory properties of thalamic neurons. In black, usual Na+ dependent spike is followed by an after hyperpolarization generated by the classical voltage-sensitive K+ conductance. Depending on membrane potential, this event can be followed by a persistent sodium current [(gNa(Ip)) black spikes]. Following an inhibitory synaptic potential a hyperpolarization dependant deinactivation of type a gCa (T) conductance, and the simultaneous inactivation of the potassium conductance gK(Ih) together generate a rebound response (green). The membrane potential is brought back to the threshold for the fast spike by the slow potassium conductance. In addition to the 10-Hz oscillations, slower oscillations (about 6 Hz) can occur by the rebound excitation (blue trace) following hyperpolarization of the cell [gK (Ca)] and inhibitory postsynaptic potentials (IPSPs). Such hyperpolarization deinactivates the low-threshold Ca2+ conductance generating a rebound low threshold spike, which triggers the process once again activating potassium conductance (Ih). (Jahnsen and Llinás, ,; McCormick and Prince, 1986).
Figure 13
Figure 13
In vitro intracellular recording from a sparsely spinous neuron of the fourth layer of the frontal cortex of guinea pig. (A) Characteristic response obtained in the cell following direct depolarization, consisting of sustained subthreshold oscillatory activity on which single spikes can be observed. (B) Autocorrelogram of the intrinsic oscillatory frequency indicated a 42 Hz intrinsic oscillation (Llinás et al., 1991).
Figure 14
Figure 14
Diagram of the proposed cortico-thalamo-cortical reverberating circuit, which may underlie 40-Hz oscillation at the cortex. See text.
Figure 15
Figure 15
Magnetoencephalographic (MEG) recordings in three functional states. (A) Magnetic recording demonstrating gamma band activity following a sensory stimulus in awake subject. (B) Recordings from same subject during deep, dreamless sleep. (C) Gamma band activity while dreaming. (D) Instrument noise in the absence of a subject. (E) Localization of gamma band activity in an awake subject note frontal and parietal and temporal association lobe activity. (F) Localization of gamma band activity recorded when the subject was dreaming. Note the lack of frontal lobe activity and the powerful activation of the temporal pole. (Llinás and Ribary, and unpublished observations.).

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