scholarly journals A model of on/off transitions in neurons of the deep cerebellar nuclei: deciphering the underlying ionic mechanisms

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hugues Berry ◽  
Stéphane Genet
Keyword(s):  
Cerebellar Nuclei ◽  
Biophysical Model ◽  
High Threshold ◽  
Deep Cerebellar Nuclei ◽  
Functional Link ◽  
Electrophysiological Properties ◽  
Voltage Dependent ◽  
Ionic Mechanisms ◽  
The Central Nervous System ◽  
Overall Functioning

AbstractThe neurons of the deep cerebellar nuclei (DCNn) represent the main functional link between the cerebellar cortex and the rest of the central nervous system. Therefore, understanding the electrophysiological properties of DCNn is of fundamental importance to understand the overall functioning of the cerebellum. Experimental data suggest that DCNn can reversibly switch between two states: the firing of spikes (F state) and a stable depolarized state (SD state). We introduce a new biophysical model of the DCNn membrane electro-responsiveness to investigate how the interplay between the documented conductances identified in DCNn give rise to these states. In the model, the F state emerges as an isola of limit cycles, i.e. a closed loop of periodic solutions disconnected from the branch of SD fixed points. This bifurcation structure endows the model with the ability to reproduce the $\text{F}\to \text{SD}$ F → SD transition triggered by hyperpolarizing current pulses. The model also reproduces the $\text{F}\to \text{SD}$ F → SD transition induced by blocking Ca currents and ascribes this transition to the blocking of the high-threshold Ca current. The model suggests that intracellular current injections can trigger fully reversible $\text{F}\leftrightarrow \text{SD}$ F ↔ SD transitions. Investigation of low-dimension reduced models suggests that the voltage-dependent Na current is prominent for these dynamical features. Finally, simulations of the model suggest that physiological synaptic inputs may trigger $\text{F}\leftrightarrow \text{SD}$ F ↔ SD transitions. These transitions could explain the puzzling observation of positively correlated activities of connected Purkinje cells and DCNn despite the former inhibit the latter.

scholarly journals Electrophysiological Properties of Inferior Olive Neurons: A Compartmental Model

1999 ◽  
Vol 82 (2) ◽  
pp. 804-817 ◽  
Author(s):  
Nicolas Schweighofer ◽  
Kenji Doya ◽  
Mitsuo Kawato
Keyword(s):  
Calcium Current ◽  
Potassium Current ◽  
Inferior Olive ◽  
Sodium Current ◽  
Electrical Coupling ◽  
Biophysical Model ◽  
Delayed Rectifier ◽  
High Threshold ◽  
Electrophysiological Properties

As a step in exploring the functions of the inferior olive, we constructed a biophysical model of the olivary neurons to examine their unique electrophysiological properties. The model consists of two compartments to represent the known distribution of ionic currents across the cell membrane, as well as the dendritic location of the gap junctions and synaptic inputs. The somatic compartment includes a low-threshold calcium current ( I Ca_l), an anomalous inward rectifier current ( I h), a sodium current ( I Na), and a delayed rectifier potassium current ( I K_dr). The dendritic compartment contains a high-threshold calcium current ( I Ca_h), a calcium-dependent potassium current ( I K_Ca), and a current flowing into other cells through electrical coupling ( I c). First, kinetic parameters for these currents were set according to previously reported experimental data. Next, the remaining free parameters were determined to account for both static and spiking properties of single olivary neurons in vitro. We then performed a series of simulated pharmacological experiments using bifurcation analysis and extensive two-parameter searches. Consistent with previous studies, we quantitatively demonstrated the major role of I Ca_l in spiking excitability. In addition, I h had an important modulatory role in the spike generation and period of oscillations, as previously suggested by Bal and McCormick. Finally, we investigated the role of electrical coupling in two coupled spiking cells. Depending on the coupling strength, the hyperpolarization level, and the I Ca_l and I hmodulation, the coupled cells had four different synchronization modes: the cells could be in-phase, phase-shifted, or anti-phase or could exhibit a complex desynchronized spiking mode. Hence these simulation results support the counterintuitive hypothesis that electrical coupling can desynchronize coupled inferior olive cells.

Postsynaptic Currents in Deep Cerebellar Nuclei

2001 ◽  
Vol 85 (1) ◽  
pp. 323-331 ◽  
Author(s):  
Davide Anchisi ◽  
Bibiana Scelfo ◽  
Filippo Tempia
Keyword(s):  
Nmda Receptors ◽  
Time Constant ◽  
Exponential Decay ◽  
Reversal Potential ◽  
Cerebellar Nuclei ◽  
Deep Cerebellar Nuclei ◽  
Time Constants ◽  
Postsynaptic Currents ◽  
Voltage Dependent ◽  
Single Exponential

Postsynaptic currents were studied by whole cell recordings in visually identified large neurons of the deep cerebellar nuclei (DCN) in slices of 4- to 11-day-old mice. Spontaneous postsynaptic currents were abolished by the GABAA receptor antagonist bicuculline and had a single-exponential decay with a mean time constant of 13.6 ± 3.2 (SD) ms. Excitatory postsynaptic currents (EPSCs) were evoked in 48/56 neurons recorded. The addition of AMPA and N-methyl-d-aspartate (NMDA) receptor antagonists together completely abolished all synaptic responses. In 1 mM [Mg2+]o and at a holding potential of −60 mV, the peak amplitude of the NMDA component of the EPSC (NMDA-EPSC) was 83.2 ± 21.2% of the AMPA component (AMPA-EPSC). This indicates that in DCN neurons, at a physiological [Mg2+]o and at the resting membrane potential, NMDA receptors contribute to the synaptic signal. AMPA-EPSCs had a linear current-voltage relationship with a reversal potential of +2.3 ± 0.4 mV and a single-exponential decay with a voltage-dependent time constant that at −60 mV was 7.1 ± 3.3 ms. In 10 μM glycine and 1 mM [Mg2+]o, the I-V relationship of NMDA-EPSCs had a reversal potential of −0.5 ± 3.3 mV and a maximal inward current at −33.4 ± 5.8 mV. The apparent dissociation constant ( K D) of Mg2+ for the NMDA receptor-channel at −60 mV, measured by varying [Mg2+]o, was 135.5 ± 55.3 μM, and when measured by fitting the I-V curves with a theoretical function, it was 169.9 ± 119.5 μM. Thus in the DCN, NMDA receptors have a sensitivity to Mg2+ that corresponds to subunits that are weakly blocked by this ion (ε3 and ε4) of which the DCN express ε4. NMDA-EPSCs had a double-exponential decay with voltage-dependent time constants that at −60 mV were 20.2 ± 8.9 and 136.4 ± 62.8 ms. At positive voltages, the time constants were slower and their contributions were about equal, while in the negative slope conductance region of the I-V curve, the faster time constant became predominant, conferring faster kinetics to the EPSC. The weak sensitivity to Mg2+ of NMDA receptors, together with a relatively fast kinetics, provide DCN neurons with strong excitatory inputs in which fast dynamic signals are relatively well preserved.

Morphological and Electrophysiological Properties of GABAergic and Non-GABAergic Cells in the Deep Cerebellar Nuclei

2007 ◽  
Vol 97 (1) ◽  
pp. 901-911 ◽  
Author(s):  
Marylka Uusisaari ◽  
Kunihiko Obata ◽  
Thomas Knöpfel
Keyword(s):  
Fluorescent Protein ◽  
Cerebellar Nuclei ◽  
Spike Rate ◽  
Deep Cerebellar Nuclei ◽  
Homogeneous Population ◽  
Electrophysiological Properties ◽  
Glutamatergic Neurons ◽  
Green Fluorescent ◽  
The Brain ◽  
High Firing

The deep cerebellar nuclei (DCN) integrate inputs from the brain stem, the inferior olive, and the spinal cord with Purkinje cell output from cerebellar cortex and provide the major output of the cerebellum. Despite their crucial function in motor control and learning, the various populations of neurons in the DCN are poorly defined and characterized. Importantly, differences in electrophysiological properties between glutamatergic and GABAergic cells of the DCN have been largely elusive. Here, we used glutamate decarboxylase (GAD) 67-green fluorescent protein (GFP) knock-in mice to unambiguously identify GABAergic (GAD-positive) and non-GABAergic (GAD-negative, most likely glutamatergic) neurons of the DCN. Morphological analysis of DCN neurons patch-clamped with biocytin-containing electrodes revealed a significant overlap in the distributions of the soma sizes of GAD-positive and GAD-negative cells. Compared with GAD-negative DCN neurons, GAD-positive DCN neurons fire broader action potentials, display stronger frequency accommodation, and do not reach as high firing frequencies during depolarizing current injections. Furthermore, GAD-positive cells display slower spontaneous firing rates and have a more shallow frequency-to-current relationship than the GAD-negative cells but exhibit a longer-lasting rebound depolarization and associated spiking after a transient hyperpolarization. In contrast to the rather homogeneous population of GAD-positive cells, the GAD-negative cells were found to consist of two distinct populations as defined by cell size and electrophysiological features. We conclude that GABAergic DCN neurons are specialized to convey phasic spike rate information, whereas tonic spike rate is more faithfully relayed by the large non-GABAergic cells.

Electrophysiology of the mammillary complex in vitro. II. Medial mammillary neurons

1992 ◽  
Vol 68 (4) ◽  
pp. 1321-1331 ◽  
Author(s):  
A. Alonso ◽  
R. R. Llinas
Keyword(s):  
Low Frequency ◽  
Input Resistance ◽  
Resting Potential ◽  
High Threshold ◽  
Potential Oscillations ◽  
Electrophysiological Properties ◽  
Voltage Dependent ◽  
Low Threshold ◽  
Membrane Potential Oscillations

1. The electrophysiological properties of guinea pig medial mammillary body (MMB) neurons were studied using an in vitro slice preparation. 2. The neurons (n = 80) had an average resting potential of -57 +/- 5.5 (SD) mV, an input resistance of 176 +/- 83 M omega, and a spike amplitude of 58 +/- 15.7 mV. Most of the neurons were silent at rest (n = 52), but some fired spontaneous single spikes (n = 16) or spike bursts (n = 14). 3. The main electrophysiological characteristic of MMB neurons was the ability to generate Ca(2+)-dependent regenerative events, which resulted in very robust burst responses. However, this regenerative event was not the same for all neurons, ranging from typical low-threshold Ca2+ spikes (LTSs) to intermediate-threshold plateau potentials (ITPs). 4. The ITPs were distinct from the LTSs in that they lasted > or = 100 ms and were not inactivated at membrane potentials at or positive to -55 mV. 5. Some cells with a prominent ITP and no LTS (n = 36) displayed repetitive, usually rhythmic, bursting (n = 14). This ITP could be powerful enough to maintain rhythmic membrane potential oscillations after pharmacological block of Na+ conductances. 6. A group of 32 MMB neurons displayed complex bursting that was generated by activation of both LTSs and ITPs. This was established on the basis of their distinct time- and voltage-dependent characteristics. In a group of neurons (n = 14), the burst responses were exclusively generated by an LTS; however, a Ca(2+)-dependent plateau potential contributed to the generation of rebound-triggered oscillatory firing. 7. In addition to the Ca(2+)-dependent LTS and/or ITP, MMB neurons always displayed high-threshold Ca2+ spikes after reduction of K+ conductances with tetraethylammonium. 8. MMB neurons display one of the richer varieties of voltage-dependent Ca2+ conductances so far encountered in mammalian CNS. We propose that the very prominent endogenous bursting and oscillatory properties of MB neurons allow this nuclear complex to function as an oscillatory relay for the transmission of low-frequency rhythmic activities throughout the limbic circuit.

scholarly journals Mapping of long-term cognitive and motor deficits in pediatric cerebellar brain tumor survivors into a cerebellar white matter atlas

2021 ◽  
Author(s):  
Frederik Grosse ◽  
Stefan Mark Rueckriegel ◽  
Ulrich-Wilhelm Thomale ◽  
Pablo Hernáiz Driever
Keyword(s):  
Brain Tumor ◽  
Executive Function ◽  
Cognitive Function ◽  
White Matter ◽  
Cerebellar Nuclei ◽  
Motor Deficits ◽  
Deep Cerebellar Nuclei ◽  
Cerebellar White Matter ◽  
Lesion Symptom Mapping

Abstract Purpose Diaschisis of cerebrocerebellar loops contributes to cognitive and motor deficits in pediatric cerebellar brain tumor survivors. We used a cerebellar white matter atlas and hypothesized that lesion symptom mapping may reveal the critical lesions of cerebellar tracts. Methods We examined 31 long-term survivors of pediatric posterior fossa tumors (13 pilocytic astrocytoma, 18 medulloblastoma). Patients underwent neuronal imaging, examination for ataxia, fine motor and cognitive function, planning abilities, and executive function. Individual consolidated cerebellar lesions were drawn manually onto patients’ individual MRI and normalized into Montreal Neurologic Institute (MNI) space for further analysis with voxel-based lesion symptom mapping. Results Lesion symptom mapping linked deficits of motor function to the superior cerebellar peduncle (SCP), deep cerebellar nuclei (interposed nucleus (IN), fastigial nucleus (FN), ventromedial dentate nucleus (DN)), and inferior vermis (VIIIa, VIIIb, IX, X). Statistical maps of deficits of intelligence and executive function mapped with minor variations to the same cerebellar structures. Conclusion We identified lesions to the SCP next to deep cerebellar nuclei as critical for limiting both motor and cognitive function in pediatric cerebellar tumor survivors. Future strategies safeguarding motor and cognitive function will have to identify patients preoperatively at risk for damage to these critical structures and adapt multimodal therapeutic options accordingly.

scholarly journals Cerebellar Theta-Burst Stimulation Impairs Memory Consolidation in Eyeblink Classical Conditioning

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Jessica Monaco ◽  
Lorenzo Rocchi ◽  
Francesca Ginatempo ◽  
Egidio D'Angelo ◽  
John C. Rothwell
Keyword(s):  
Classical Conditioning ◽  
Cerebellar Nuclei ◽  
Cerebellar Hemisphere ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Deep Cerebellar Nuclei ◽  
Significant Impairment ◽  
Conditioned Responses ◽  
The Right ◽  
Theta Burst

Associative learning of sensorimotor contingences, as it occurs in eyeblink classical conditioning (EBCC), is known to involve the cerebellum, but its mechanism remains controversial. EBCC involves a sequence of learning processes which are thought to occur in the cerebellar cortex and deep cerebellar nuclei. Recently, the extinction phase of EBCC has been shown to be modulated after one week by cerebellar continuous theta-burst stimulation (cTBS). Here, we asked whether cerebellar cTBS could affect retention and reacquisition of conditioned responses (CRs) tested immediately after conditioning. We also investigated a possible lateralized cerebellar control of EBCC by applying cTBS on both the right and left cerebellar hemispheres. Both right and left cerebellar cTBSs induced a statistically significant impairment in retention and new acquisition of conditioned responses (CRs), the disruption effect being marginally more effective when the left cerebellar hemisphere was stimulated. These data support a model in which cTBS impairs retention and reacquisition of CR in the cerebellum, possibly by interfering with the transfer of memory to the deep cerebellar nuclei.

Comparative immunohistochemical distribution of amylin-like and calcitonin gene related peptide like immunoreactivity in the rat central nervous system

1995 ◽  
Vol 73 (7) ◽  
pp. 945-956 ◽  
Author(s):  
Gerhard Skofitseh ◽  
Wolfgang Gubisch ◽  
Sunil J. Wimalawansa ◽  
David M. Jacobowitz
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cerebellar Nuclei ◽  
Calcitonin Gene Related Peptide ◽  
Polyclonal Antiserum ◽  
Related Peptide ◽  
Diagonal Band ◽  
Large Numbers ◽  
Calcitonin Gene ◽  
The Central Nervous System

Using the indirect immunofluorescence method with a polyclonal antiserum raised in rabbits and directed against amylin (AMY), we have investigated the distribution of AMY-like immunoreactivity (-ir) throughout the central nervous system of the rat. The widespread distribution of AMY-ir was much more abundant than that previously reported for calcitonin gene related peptide (CGRP) immunoreactivity. In most brain areas there was no overlap between AMY- and CGRP-ir cell body groupings, with the exception of the motor nuclei of the hindbrain and spinal cord, which were found to contain large numbers of AMY- and CGRP-immunoreactive cell bodies. Areas with a moderate to dense appearance of AMY-ir were the rhinencephalon, the nucleus of the diagonal band, the magnocellular, dorso- and ventro-medial and mammillary nuclei of the hypothalamus, the habenula, the compact part of the substantia nigra, the ruber and pontine nuclei, and the inferior olive and the cerebellar nuclei. The widespread immunohistochemical distribution of AMY-ir in the rat brain is in partial agreement with the distribution of AMY-binding sites.Key words: calcitonin gene related peptide, amylin, central nervous system, immunohistochemistry, rat.

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