Spatial Distribution of Synaptically Activated Sodium Concentration Changes in Cerebellar Purkinje Neurons

1997 ◽  
Vol 77 (1) ◽  
pp. 145-152 ◽  
Author(s):  
Joseph C. Callaway ◽  
William N. Ross
Keyword(s):  
Spatial Distribution ◽  
Purkinje Cells ◽  
Cell Body ◽  
Action Potentials ◽  
Sodium Concentration ◽  
Purkinje Neuron ◽  
Climbing Fiber ◽  
Purkinje Neurons ◽  
Concentration Changes ◽  
Cerebellar Purkinje Neurons

Callaway, Joseph C. and William N. Ross. Spatial distribution of synaptically activated sodium concentration changes in cerebellar Purkinje neurons. J. Neurophysiol. 77: 145–152, 1997. The spatial distribution of Na+-dependent events in guinea pig Purkinje cells was studied with a combination of high-speed imaging and simultaneous intracellular recording. Individual Purkinje cells in sagittal cerebellar slices were loaded with either fura-2 or the Na+ indicator sodium binding benzofuran isophthalate (SBFI) with sharp electrodes or patch electrodes on the soma or dendrites. [Na+]i changes were detected in response to climbing fiber and parallel fiber stimulation. These changes were located both at the anatomically expected sites of synaptic contact in the dendrites and in the somatic region. The variation in time course of these [Na+]i changes in different locations implies that Na+ enters at the synapse and diffuses rapidly to locations of lower initial [Na+]i. The synaptically activated somatic [Na+]i changes probably reflect Na+ entry through voltage-sensitive Na+ channels because they were detected only when regenerative potentials were recorded in the soma. [Na+]i changes in response to antidromically or intrasomatically evoked Na+ action potentials also were confined to the cell body. These observations are in agreement with other evidence that Na+ spikes are generated in the somatic region of the Purkinje neuron and spread passively into the dendrites. Plateau potentials, evoked by depolarizing pulses to the soma or dendrites, caused [Na+]i changes only in the soma, indicating that the noninactivating Na+ channels contributing to this potential also were concentrated in this region. The climbing fiber-activated [Na+]i changes were blocked by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione, indicating that these changes were not due to direct stimulation of the Purkinje neuron or activation of metabotropic receptors. Direct depolarization of the soma or dendrites never caused dendritic [Na+]i increases, suggesting that the climbing fiber-activated [Na+]i changes in the dendrites are due to Na+ entry through ligand-gated channels. A climbing fiber-like regenerative potential could be recorded in the soma after anode break stimulation, parallel fiber activation, or depolarizing pulses to the soma. The [Na+]i changes evoked by all of these potentials were confined to the cell body region of the Purkinje cell. [Ca2+]i changes in the dendrites evoked by the anode break potential were small relative to climbing fiber-activated changes, suggesting that a Ca2+ spike was not evoked by this response. The anode break and directly responses were blocked by tetrodotoxin. These results suggest that the somatically recorded climbing fiber response is predominantly a Na+-dependent event, consisting of a few fast action potentials and a slower regenerative response activating the same channels as the Na+ plateau potential.

Sodium Imaging of Climbing Fiber Innervation Fields in Developing Mouse Purkinje Cells

2003 ◽  
Vol 89 (5) ◽  
pp. 2555-2563 ◽  
Author(s):  
Bibiana Scelfo ◽  
Piergiorgio Strata ◽  
Thomas Knöpfel
Keyword(s):  
Nervous System ◽  
Purkinje Cell ◽  
Purkinje Cells ◽  
Cell Body ◽  
Sodium Concentration ◽  
Climbing Fiber ◽  
Early Postnatal Development ◽  
Postsynaptic Currents ◽  
Sodium Imaging ◽  
Neuronal Connections

Maturation of specific neuronal connections in the mature nervous system includes elimination of redundant synapses formed earlier during development. In the cerebellum of adult animals, each Purkinje cell (PC) is innervated by a single climbing fiber (CF). In early postnatal development each PC is innervated by multiple CFs and elimination of synapses formed by supernumerary CFs occurs until monoinnervation is established at around postnatal day 20 (P20) in mice. It is not clear whether multiple CFs, or only a single CF, translocate from the cell body of immature PCs to the developing dendrite and, in case several CFs translocate, whether they share or segregate their innervation fields. To localize CF innervation fields, we imaged changes in postsynaptic sodium concentration resulting from CF-mediated postsynaptic currents. We found that more than one CF translocates from an innervation field on the cell body of the PC to the developing dendrite and that these CFs share rather than segregate their innervation fields. We concluded that both the soma and the proximal dendrite of the PC are territories of competition for the developing CFs and that the overlapping of their termination fields may be the prerequisite for a local process of elimination of all but one CF, as previously demonstrated in the developing neuromuscular junction.

scholarly journals Altered Capicua expression drives regional Purkinje neuron vulnerability through ion channel gene dysregulation in spinocerebellar ataxia type 1

2020 ◽  
Vol 29 (19) ◽  
pp. 3249-3265
Author(s):  
Ravi Chopra ◽  
David D Bushart ◽  
John P Cooper ◽  
Dhananjay Yellajoshyula ◽  
Logan M Morrison ◽  
...  
Keyword(s):  
Ion Channel ◽  
Spinocerebellar Ataxia ◽  
Selective Vulnerability ◽  
Purkinje Neuron ◽  
Purkinje Neurons ◽  
Spinocerebellar Ataxia Type ◽  
Spinocerebellar Ataxia Type 1 ◽  
Gene Dysregulation ◽  
Cerebellar Purkinje Neurons

Abstract Selective neuronal vulnerability in neurodegenerative disease is poorly understood. Using the ATXN1[82Q] model of spinocerebellar ataxia type 1 (SCA1), we explored the hypothesis that regional differences in Purkinje neuron degeneration could provide novel insights into selective vulnerability. ATXN1[82Q] Purkinje neurons from the anterior cerebellum were found to degenerate earlier than those from the nodular zone, and this early degeneration was associated with selective dysregulation of ion channel transcripts and altered Purkinje neuron spiking. Efforts to understand the basis for selective dysregulation of channel transcripts revealed modestly increased expression of the ATXN1 co-repressor Capicua (Cic) in anterior cerebellar Purkinje neurons. Importantly, disrupting the association between ATXN1 and Cic rescued the levels of these ion channel transcripts, and lentiviral overexpression of Cic in the nodular zone accelerated both aberrant Purkinje neuron spiking and neurodegeneration. These findings reinforce the central role for Cic in SCA1 cerebellar pathophysiology and suggest that only modest reductions in Cic are needed to have profound therapeutic impact in SCA1.

scholarly journals Ryanodine and inositol trisphosphate receptors coexist in avian cerebellar Purkinje neurons.

1991 ◽  
Vol 113 (5) ◽  
pp. 1145-1157 ◽  
Author(s):  
P D Walton ◽  
J A Airey ◽  
J L Sutko ◽  
C F Beck ◽  
G A Mignery ◽  
...  
Keyword(s):  
Calcium Release ◽  
Inositol Trisphosphate ◽  
Ryanodine Receptors ◽  
Dendritic Tree ◽  
Purkinje Neuron ◽  
Purkinje Neurons ◽  
Branch Points ◽  
Calcium Release Channel ◽  
Cerebellar Purkinje Neurons ◽  
Insp3 Receptor

Two intracellular calcium-release channel proteins, the inositol trisphosphate (InsP3), and ryanodine receptors, have been identified in mammalian and avian cerebellar Purkinje neurons. In the present study, biochemical and immunological techniques were used to demonstrate that these proteins coexist in the same avian Purkinje neurons, where they have different intracellular distributions. Western analyses demonstrate that antibodies produced against the InsP3 and the ryanodine receptors do not cross-react. Based on their relative rates of sedimentation in continuous sucrose gradients and SDS-PAGE, the avian cerebellar InsP3 receptor has apparent native and subunit molecular weights of approximately 1,000 and 260 kD, while those of the ryanodine receptors are approximately 2,000 and 500 kD. Specific [3H]InsP3- and [3H]ryanodine-binding activities were localized in the sucrose gradient fractions enriched in the 260-kD and the approximately 500-kD polypeptides, respectively. Under equilibrium conditions, cerebellar microsomes bound [3H]InsP3 with a Kd of 16.8 nM and Bmax of 3.8 pmol/mg protein; whereas, [3H]ryanodine was bound with a Kd of 1.5 nM and a capacity of 0.08 pmol/mg protein. Immunolocalization techniques, applied at both the light and electron microscopic levels, revealed that the InsP3 and ryanodine receptors have overlapping, yet distinctive intracellular distributions in avian Purkinje neurons. Most notably the InsP3 receptor is localized in endomembranes of the dendritic tree, in both the shafts and spines. In contrast, the ryanodine receptor is observed in dendritic shafts, but not in the spines. Both receptors appear to be more abundant at main branch points of the dendritic arbor. In Purkinje neuron cell bodies, both the InsP3 and ryanodine receptors are present in smooth and rough ER, subsurface membrane cisternae and to a lesser extent in the nuclear envelope. In some cases the receptors coexist in the same membranes. Neither protein is observed at the plasma membrane, Golgi complex or mitochondrial membranes. Both the InsP3 and ryanodine receptors are associated with intracellular membrane systems in axonal processes, although they are less abundant there than in dendrites. These data demonstrate that InsP3 and ryanodine receptors exist as unique proteins in the same Purkinje neuron. These calcium-release channels appear to coexist in ER membranes in most regions of the Purkinje neurons, but importantly they are differentially distributed in dendritic processes, with the dendritic spines containing only InsP3 receptors.

scholarly journals Altered Capicua expression drives regional Purkinje neuron vulnerability through ion channel gene dysregulation in Spinocerebellar ataxia type 1

2020 ◽  
Author(s):  
Ravi Chopra ◽  
David D Bushart ◽  
John P Cooper ◽  
Dhananjay Yellajoshyula ◽  
Logan M Morrison ◽  
...  
Keyword(s):  
Ion Channel ◽  
Spinocerebellar Ataxia ◽  
Selective Vulnerability ◽  
Purkinje Neuron ◽  
Purkinje Neurons ◽  
Spinocerebellar Ataxia Type ◽  
Spinocerebellar Ataxia Type 1 ◽  
Gene Dysregulation ◽  
Cerebellar Purkinje Neurons

AbstractSelective neuronal vulnerability in neurodegenerative disease is poorly understood. Using the ATXN1[82Q] model of spinocerebellar ataxia type 1 (SCA1), we explored the hypothesis that regional differences in Purkinje neuron degeneration could provide novel insights into selective vulnerability. ATXN1[82Q] Purkinje neurons from the anterior cerebellum were found to degenerate earlier than those from the nodular zone, and this early degeneration was associated with selective dysregulation of ion channel transcripts and altered Purkinje neuron spiking. Efforts to understand the basis for selective dysregulation of channel transcripts revealed modestly increased expression of the ATXN1 corepressor Capicua (Cic) in anterior cerebellar Purkinje neurons. Importantly, lentiviral overexpression of Cic in the nodular zone accelerated both aberrant Purkinje neuron spiking and neurodegeneration. These findings reinforce the central role for Cic in SCA1 cerebellar pathophysiology and suggest that only modest reductions in Cic are needed to have profound therapeutic impact in SCA1.

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