Effects Produced by Local Applications of Harmaline in the Inferior Olive

1975 ◽  
Vol 53 (5) ◽  
pp. 845-849 ◽  
Author(s):  
C. De Montigny ◽  
Y. Lamarre
Keyword(s):  
Inferior Olive ◽  
Rhythmic Activity ◽  
Coupling Mechanism ◽  
Electrotonic Coupling ◽  
Accessory Nuclei ◽  
Inferior Olivary ◽  
Decerebrate Cats ◽  
Inferior Olivary Complex

Local microinjections of harmaline evoked sustained rhythmic activity in the inferior olive of decerebrate cats. Harmaline appears to exert its action within restricted areas of the inferior olivary complex: the caudal halves of the dorsal and medial accessory nuclei. Since the highly synchronized activity generated by harmaline can be attributed to extensive electrotonic coupling between olivary neurones, it is postulated that such a coupling mechanism is weaker if not absent in the principal olive and in the rostral parts of the accessory nuclei.

Induction of Rhythmic Activity by Harmaline

1974 ◽  
Vol 52 (4) ◽  
pp. 905-908 ◽  
Author(s):  
Y. Lamarre ◽  
E. Puil
Keyword(s):  
High Frequency ◽  
Inferior Olive ◽  
Rhythmic Activity ◽  
Multiunit Activity ◽  
Strong Excitation ◽  
Decerebrate Cats

Microiontophoretic application of harmaline evoked rhythmic multiunit activity in the inferior olive of decerebrate cats. Harmaline caused strong excitation of individual olivary neurones but did not seem to cause them to discharge in high frequency bursts. These effects suggest that the tremorgenic action of harmaline may be due to an exaggeration of the normal tendency of olivary neurones to fire rhythmically in multiunit bursts.

scholarly journals Quasiperiodic Rhythms of the Inferior Olive

2018 ◽  
Author(s):  
Mario Negrello ◽  
Pascal Warnaar ◽  
Vincenzo Romano ◽  
Cullen B Owens ◽  
Sander Lindeman ◽  
...  
Keyword(s):  
Inferior Olive ◽  
Rhythmic Activity ◽  
Sensory Stimulation ◽  
Short Term ◽  
Subthreshold Oscillations ◽  
Electrophysiological Recordings ◽  
Long Term Changes ◽  
Inferior Olivary ◽  
Spiking Activity

Inferior olivary activity causes both short-term and long-term changes in cerebellar output underlying motor performance and motor learning. Many of its neurons engage in coherent subthreshold oscillations and are extensively coupled via gap junctions. Studies in reduced preparations suggest that these properties promote rhythmic, synchronized output. However, how these properties interact with synaptic inputs controlling inferior olivary output in intact, awake behaving animals is poorly understood. Here we combine electrophysiological recordings in awake mice with a novel and realistic tissue-scale computational model of the inferior olive to study the relative impact of intrinsic and extrinsic mechanisms governing its activity. Our data and model suggest that if subthreshold oscillations are present in the awake state, the period of these oscillations will be transient and variable. Accordingly, by using different temporal patterns of sensory stimulation, we found that complex spike rhythmicity was readily evoked but limited to short intervals of no more than a few hundred milliseconds and that the periodicity of this rhythmic activity was not fixed but dynamically related to the synaptic input to the inferior olive as well as to motor output. In contrast, in the long-term the average olivary spiking activity was not affected by the strength and duration of the sensory stimulation, while the level of gap junctional coupling determined the stiffness of the rhythmic activity in the olivary network during its dynamic response to sensory modulation. Thus, interactions between intrinsic properties and extrinsic inputs can explain the variations of spiking activity of olivary neurons, providing a conceptual framework for the creation of both the short-term and long-term changes in cerebellar output.

The embryonic cerebellum contains topographic cues that guide developing inferior olivary axons

Development ◽  
1997 ◽  
Vol 124 (4) ◽  
pp. 861-870 ◽  
Author(s):  
A. Chedotal ◽  
E. Bloch-Gallego ◽  
C. Sotelo
Keyword(s):  
Inferior Olive ◽  
Positional Information ◽  
Original Position ◽  
Chick Embryos ◽  
In Vitro Experiments ◽  
In Vitro System ◽  
Target Region ◽  
Inferior Olivary ◽  
Anteroposterior Polarity

The formation of the olivocerebellar projection is supposed to be regulated by positional information shared between pre- and postsynaptic neurons. However, experimental evidence to support this hypothesis is missing. In the chick, caudal neurons in the inferior olive project to the anterior cerebellum and rostral ones to the posterior cerebellum. We here report in vitro experiments that strongly support the existence of anteroposterior polarity cues in the embryonic cerebellum. We developed an in vitro system that was easily accessible to experimental manipulations. Large hindbrain explants of E7.5-E8 chick embryos, containing the cerebellum and its attached brainstem, were plated and studied using axonal tracing methods. In these cultures, we have shown that the normal anteroposterior topography of the olivocerebellar projection was acquired, even when the cerebellar lamella was detached from the brainstem and placed again in its original position. We also found that, following various experimental rotations of the anteroposterior axis of the cerebellum, the rostromedian olivary neurons still project to the posterior vermis and the caudolateral neurons to the anterior vermis, that now have inverted locations. Thus, the rotation of the target region results in the rotation of the projection. In addition, we have shown that the formation of the projection map could be due to the inability of rostromedian inferior olivary axons to grow in the anterior cerebellum. All these experiments strongly indicate that olivocerebellar fibers recognize within their target region polarity cues that organize their anteroposterior topography, and we suggest that Purkinje cells might carry these cues.

scholarly journals Low-Amplitude Oscillations in the Inferior Olive: A Model Based on Electrical Coupling of Neurons With Heterogeneous Channel Densities

1997 ◽  
Vol 77 (5) ◽  
pp. 2736-2752 ◽  
Author(s):  
Yair Manor ◽  
John Rinzel ◽  
Idan Segev ◽  
Yosef Yarom
Keyword(s):  
Inferior Olive ◽  
Electrical Coupling ◽  
The Other ◽  
Sustained Oscillation ◽  
Large Coupling ◽  
Model Based ◽  
Subthreshold Oscillations ◽  
Coupling Current ◽  
Low Amplitude ◽  
Inferior Olivary

Manor, Yair, John Rinzel, Idan Segev, and Yosef Yarom. Low-amplitude oscillations in the inferior olive: a model based on electrical coupling of neurons with heterogeneous channel densities. J. Neurophysiol. 77: 2736–2752, 1997. The mechanism underlying subthreshold oscillations in inferior olivary cells is not known. To study this question, we developed a single-compartment, two-variable, Hodgkin-Huxley-like model for inferior olive neurons. The model consists of a leakage current and a low-threshold calcium current, whose kinetics were experimentally measured in slices. Depending on the maximal calcium and leak conductances, we found that a neuron model's response to current injection could be of four qualitatively different types: always stable, spontaneously oscillating, oscillating with injection of current, and bistable with injection of current. By the use of phase plane techniques, numerical integration, and bifurcation analysis, we subdivided the two-parameter space of channel densities into four regions corresponding to these behavioral types. We further developed, with the use of such techniques, an empirical rule of thumb that characterizes whether two cells when coupled electrically can generate sustained, synchronized oscillations like those observed in inferior olivary cells in slices, of low amplitude (0.1–10 mV) in the frequency range 4–10 Hz. We found that it is not necessary for either cell to be a spontaneous oscillator to obtain a sustained oscillation. On the other hand, two spontaneous oscillators always form an oscillating network when electrically coupled with any arbitrary coupling conductance. In the case of an oscillating pair of electrically coupled nonidentical cells, the coupling current varies periodically and is nonzero even for very large coupling values. The coupling current acts as an equalizing current to reconcile the differences between the two cells' ionic currents. It transiently depolarizes one cell and/or hyperpolarizes the other cell to obtain the regenerative response(s) required for the synchronized oscillation. We suggest that the subthreshold oscillations observed in the inferior olive can emerge from the electrical coupling between neurons with different channel densities, even if the inferior olive nucleus contains no or just a small proportion of spontaneously oscillating neurons.

GABAergic and Glutamatergic Modulation of Spontaneous and Motor-Cortex-Evoked Complex Spike Activity

2002 ◽  
Vol 87 (4) ◽  
pp. 1993-2008 ◽  
Author(s):  
Eric J. Lang
Keyword(s):  
Motor Cortex ◽  
Banding Pattern ◽  
Spike Activity ◽  
Afferent Input ◽  
Excitatory Input ◽  
Relative Strength ◽  
Spike Synchrony ◽  
Complex Spike ◽  
Electrotonic Coupling ◽  
Inferior Olivary

Olivocerebellar activity is organized such that synchronous complex spikes occur primarily among Purkinje cells located within the same parasagittally oriented strip of cortex. Previous findings have shown that this synchrony distribution is modulated by the release of GABA and glutamate within the inferior olive, which probably act by controlling the efficacy of the electrotonic coupling between olivary neurons. The relative strengths of these two neurotransmitters in modulating the patterns of synchrony were compared by obtaining multiple electrode recordings of spontaneous crus 2a complex spike activity during intraolivary injection of solutions containing a GABAA (picrotoxin) and/or AMPA [1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium (NBQX)] receptor antagonist. Injection of either antagonist led to increased synchrony between cells located within the same parasagittally oriented ≈250-μm-wide cortical strip. Picrotoxin also increased complex spike synchrony among cells located in different cortical strips, leading to a less prominent banding pattern, whereas injections of NBQX tended to decrease complex spike synchrony among such cells, enhancing the banding pattern. The relative strength of these two classes of olivary afferents was assessed by first injecting one of the antagonists alone and then in combination with the other. The enhanced banding pattern of complex spike synchrony following injection of NBQX alone remained during the subsequent combined injection of both antagonists. Furthermore, the widespread synchronization of complex spike activity following injection of picrotoxin alone was partially or completely reversed by combined injection of picrotoxin and NBQX. Changes in the climbing fiber reflex induced by the intraolivary injections paralleled the changes observed for spontaneous complex spike activity, indicating that the effects of picrotoxin and NBQX on the synchrony distribution reflect changes in the pattern of effective coupling of inferior olivary neurons and demonstrating that synchronous complex spike activity does not require simultaneous excitatory input to olivary cells. Finally the pattern of synchrony during motor cortical stimulation was examined. It was found that the patterns of synchrony for motor-cortex-evoked complex spike activity were similar to those of spontaneous activity, indicating an important role for electrotonic coupling in determining the response of the olivocerebellar system to afferent input. Moreover, intraolivary injections of picrotoxin increased the spatial distribution of the evoked response. In sum, the results provide evidence for the hypothesis that electrotonic coupling of inferior olivary neurons via gap junctions is the mechanism underlying complex spike synchrony and that this coupling plays an important role in determining the responses of the olivocerebellar system to synaptic input.

scholarly journals Generation and Propagation of Subthreshold Waves in a Network of Inferior Olivary Neurons

2002 ◽  
Vol 87 (6) ◽  
pp. 3059-3069 ◽  
Author(s):  
Anna Devor ◽  
Yosef Yarom
Keyword(s):  
Optical Imaging ◽  
Phase Difference ◽  
Maximum Amplitude ◽  
Nmda Receptor Antagonist ◽  
Oscillatory Activity ◽  
Electrotonic Coupling ◽  
Cell Pair ◽  
Subthreshold Oscillations ◽  
High Level ◽  
Inferior Olivary

The cells of the inferior olivary (IO) nucleus generate a large repertoire of electrical signals, among them subthreshold oscillations of the membrane potential (STO). To date, subthreshold oscillations have been studied at the level of single-cell recordings, from which network properties were inferred. In this study we used whole cell patch recordings and optical imaging to address the following issues: 1) synchrony of STO in neighboring neurons; 2) stability of the oscillatory activity in the temporal and spatial domain; and 3) the size of the oscillating network. Recordings were made from 126 pairs of IO neurons in 13- to 30-day-old rats. An additional 262 neurons were recorded individually. The frequency of STO varied from 0.8 to 8.6 Hz. The frequency distribution revealed two subpopulations with peaks at about 3 and 6 Hz. The maximum amplitude among the cells varied from 2 to 25 mV. Oscillations in most neurons showed ongoing modulations in both frequency and amplitude. These modulations were largely abolished following bath application of 40 μM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a competitive non– N-methyl-d-aspartate (non-NMDA) receptor antagonist, suggesting that they were caused by glutamatergic action. In 35 of 61 recorded pairs at least one neuron exhibited STO permitting us to compare frequency and phase relations. In 22 pairs there was coherent activity with zero phase difference between oscillations in the 2 cells. In these pairs, frequency and amplitude modulation occurred simultaneously in both neurons. Electrotonic coupling was tested in 13 pairs, that had coherent STO, and it was detected in 12. An additional seven pairs showed coherent oscillations but with a phase difference of 20–50 ms. Electrotonic coupling was observed in three of these pairs. Electrotonic coupling was also observed in two of five pairs in which only one neuron oscillated. No coupling was detected in one pair where both neurons oscillated but at different frequencies. Optical imaging using a voltage-sensitive dye (RH 414) was performed on 40 IO slices using an array of 128 photodiodes. Patches of oscillatory activity were observed in 10 slices. Among them six showed spontaneous oscillations, and four exhibited oscillations following extracellular stimulation. In agreement with cell pair recording, optical imaging demonstrated phase-shifted activity in the form of propagating waves of activity within an oscillating patch. We conclude that 1) STO exhibit ongoing modulations of frequency and amplitude that are probably caused by extrinsic inputs to the IO nucleus; 2) electrotonically coupled neurons show a high level of STO synchrony; and 3) the oscillatory activity can propagate within a network of coupled olivary neurons.

scholarly journals Harmaline Attenuates Voltage - Sensitive Ca2+ Currents in Neurons of the Inferior Olive

2012 ◽  
Vol 15 (5) ◽  
pp. 657 ◽  
Author(s):  
Xiping Zhan ◽  
Werner M Graf
Keyword(s):  
Inferior Olive ◽  
Low Voltage ◽  
Brain Slices ◽  
Cell Voltage ◽  
Current Clamp ◽  
Neuroprotective Effects ◽  
Neuron Activation ◽  
Harmala Alkaloids ◽  
Large Spike ◽  
Inferior Olivary

Purpose. Harmaline is one member of a class of tremorgenic harmala alkaloids that have been implicated in neuroprotective effects and neurodegenerative disorders. It has been reported to interact with several neurotransmitter receptors as well as ion exchangers and voltage-sensitive channels. One site of harmaline action in the brain is the inferior olive (IO). Either local or systemic harmaline injection has been reported to increase spiking rate and coherence in the inferior olive and this activation is thought to produce tremor and ataxia through inferior olivary neuron activation of target neurons in the cerebellum, but the cellular mechanism is not yet known. Methods. Here, we have performed whole cell voltage-clamp and current clamp recordings from olivary neurons in brain slices derived from newborn rats. Results. We found that both transient low-voltage activated (LVA) and sustained high voltage-activated (HVA) Ca2+ currents are significantly attenuated by 0.125 – 0.25 mM harmaline applied to the bath and that this attenuation is partially reversible. In current clamp recordings, spike-afterhyperpolarization complexes were evoked by brief positive current injections. Harmaline produced a small attenuation of spike amplitude, but large spike broadening associated with attenuation of the fast and medium afterhyperpolarization. Conclusion. Our data suggest that one mode of olivary neuron activation by harmaline involves attenuation of both HVA and LVA Ca2+ conductances and consequent attenuation of Ca2+-sensitive K+ conductances resulting in spike broadening and attenuation of the afterhyperpolarization. Both of HVA and LVA attenuation also suggests a role to regulate intracelluar Ca2+, thereby to protect neurons from apoptosis. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Sign in / Sign up

Export Citation Format

Share Document