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Presynaptic calcium signalling in cerebellar mossy fibres.

Thomsen LB, Jörntell H, Midtgaard J - Front Neural Circuits (2010)

Bottom Line: A paired-pulse depression of the calcium signal lasting more than 1 s affected burst firing in mossy fibres; this paired-pulse depression was reduced by GABA B antagonists.While our results indicated that a presynaptic rosette electrophysiologically functioned as a unit, topical GABA application showed that calcium signals in the branches of complex rosettes could be modulated locally, suggesting that cerebellar glomeruli may be dynamically sub-compartmentalized due to ongoing inhibition mediated by Golgi cells.This could provide a fine-grained control of mossy fibre-granule cell information transfer and synaptic plasticity within a mossy fibre rosette.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen Copenhagen, Denmark.

ABSTRACT
Whole-cell recordings were obtained from mossy fibre terminals in adult turtles in order to characterize the basic membrane properties. Calcium imaging of presynaptic calcium signals was carried out in order to analyse calcium dynamics and presynaptic GABA B inhibition. A tetrodotoxin (TTX)-sensitive fast Na(+) spike faithfully followed repetitive depolarizing pulses with little change in spike duration or amplitude, while a strong outward rectification dominated responses to long-lasting depolarizations. High-threshold calcium spikes were uncovered following addition of potassium channel blockers. Calcium imaging using Calcium-Green dextran revealed a stimulus-evoked all-or-none TTX-sensitive calcium signal in simple and complex rosettes. All compartments of a complex rosette were activated during electrical activation of the mossy fibre, while individual simple and complex rosettes along an axon appeared to be isolated from one another in terms of calcium signalling. CGP55845 application showed that GABA B receptors mediated presynaptic inhibition of the calcium signal over the entire firing frequency range of mossy fibres. A paired-pulse depression of the calcium signal lasting more than 1 s affected burst firing in mossy fibres; this paired-pulse depression was reduced by GABA B antagonists. While our results indicated that a presynaptic rosette electrophysiologically functioned as a unit, topical GABA application showed that calcium signals in the branches of complex rosettes could be modulated locally, suggesting that cerebellar glomeruli may be dynamically sub-compartmentalized due to ongoing inhibition mediated by Golgi cells. This could provide a fine-grained control of mossy fibre-granule cell information transfer and synaptic plasticity within a mossy fibre rosette.

No MeSH data available.


Related in: MedlinePlus

Diagram of hypothetical Golgi cell innervation patterns in a glomerulus with a complex mossy fibre rosette.  (A) In one possible scenario, Golgi cells (GoC) innervating the same glomerulus overlap in their axonal innervation territory, making a large glomerulus a functional entity. The global presynaptic inhibition of the rosette is due to summation of activity of all Golgi cells innervating the glomerulus. Control situation for (A) and (B) with no Golgi cell inhibition is indicated in Figure 7G. (B) In another scenario, no or marginal overlap of Golgi cell axons occur within a large glomerulus. Different compartments of a large complex rosette could in this way be subject to local presynaptic inhibition by different Golgi cell populations. This indicates that control of input to the cerebellar cortex could be more fine-grained than suggested by the scenario in (A), where an entire glomerulus functions as an input unit. Future anatomical analysis may allow to differentiate between these alternatives. In (B), the relative activity levels (indicated by the number and spacing of small vertical lines close to each cell) of Golgi cells may dynamically control presynaptic calcium influx in different branches of a rosette. Feedback as well as lateral-inhibition by Golgi cells could functionally compartmentalize the glomerulus. Note that the Golgi cells in the diagrams (A) and (B) represent two different cell populations and are not an indication of the actual number of Golgi cells innervating a glomerulus. Note also that the innervation scenarios depicted in (A) and (B) could be considered to illustrate opposite ends of a spectrum.
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Figure 8: Diagram of hypothetical Golgi cell innervation patterns in a glomerulus with a complex mossy fibre rosette. (A) In one possible scenario, Golgi cells (GoC) innervating the same glomerulus overlap in their axonal innervation territory, making a large glomerulus a functional entity. The global presynaptic inhibition of the rosette is due to summation of activity of all Golgi cells innervating the glomerulus. Control situation for (A) and (B) with no Golgi cell inhibition is indicated in Figure 7G. (B) In another scenario, no or marginal overlap of Golgi cell axons occur within a large glomerulus. Different compartments of a large complex rosette could in this way be subject to local presynaptic inhibition by different Golgi cell populations. This indicates that control of input to the cerebellar cortex could be more fine-grained than suggested by the scenario in (A), where an entire glomerulus functions as an input unit. Future anatomical analysis may allow to differentiate between these alternatives. In (B), the relative activity levels (indicated by the number and spacing of small vertical lines close to each cell) of Golgi cells may dynamically control presynaptic calcium influx in different branches of a rosette. Feedback as well as lateral-inhibition by Golgi cells could functionally compartmentalize the glomerulus. Note that the Golgi cells in the diagrams (A) and (B) represent two different cell populations and are not an indication of the actual number of Golgi cells innervating a glomerulus. Note also that the innervation scenarios depicted in (A) and (B) could be considered to illustrate opposite ends of a spectrum.

Mentions: If the axonal territories of Golgi cells do not overlap completely within a large complex glomerulus (Figure 8; cf. Figures 1 and 7), the restricted extracellular GABA diffusion within a glomerulus at physiological temperature (cf. Mitchell and Silver, 2000) opens the possibility that a large glomerulus may be functionally compartmentalized by local differences in extracellular GABA concentration, depending on the spatial activity pattern of Golgi cells. In this way, presynaptic inhibition by Golgi cell-mediated feedback- and lateral-inhibition to a particular glomerulus may finely regulate the mossy fibre input to specific granule cell subpopulations contacting this glomerulus (Figure 8). Evidence has previously been obtained in the cat that Golgi cell inhibition of separate mossy fibre inputs could be due to anatomically very specific distribution patterns of Golgi cell axons (Precht and Llinás, 1969), but it is presently not clear if this may be related to the scenario proposed in Figure 8. Compartmentalization of a glomerulus by Golgi cell activity (Figure 8B) may hypothetically lead to differential LTP/LTD induction (cf. Gall et al., 2005) at different mossy fibre-granule cell synapses in this glomerulus (cf. D'Angelo et al., 1999), due to spatially specific and varying degrees of Golgi cell-mediated inhibition (cf. Eccles et al., 1966; Precht and Llinás, 1969; Gabbiani et al., 1994) of voltage-dependent calcium influx in different granule cells belonging to the glomerulus. This would increase the cerebellar information storage capacity at the glomerular level compared to a scenario where each glomerulus functions as a unit. This hypothesis could be directly tested in future LTP/LTD-induction experiments by recording simultaneously from two granule cells belonging to the same glomerulus.


Presynaptic calcium signalling in cerebellar mossy fibres.

Thomsen LB, Jörntell H, Midtgaard J - Front Neural Circuits (2010)

Diagram of hypothetical Golgi cell innervation patterns in a glomerulus with a complex mossy fibre rosette.  (A) In one possible scenario, Golgi cells (GoC) innervating the same glomerulus overlap in their axonal innervation territory, making a large glomerulus a functional entity. The global presynaptic inhibition of the rosette is due to summation of activity of all Golgi cells innervating the glomerulus. Control situation for (A) and (B) with no Golgi cell inhibition is indicated in Figure 7G. (B) In another scenario, no or marginal overlap of Golgi cell axons occur within a large glomerulus. Different compartments of a large complex rosette could in this way be subject to local presynaptic inhibition by different Golgi cell populations. This indicates that control of input to the cerebellar cortex could be more fine-grained than suggested by the scenario in (A), where an entire glomerulus functions as an input unit. Future anatomical analysis may allow to differentiate between these alternatives. In (B), the relative activity levels (indicated by the number and spacing of small vertical lines close to each cell) of Golgi cells may dynamically control presynaptic calcium influx in different branches of a rosette. Feedback as well as lateral-inhibition by Golgi cells could functionally compartmentalize the glomerulus. Note that the Golgi cells in the diagrams (A) and (B) represent two different cell populations and are not an indication of the actual number of Golgi cells innervating a glomerulus. Note also that the innervation scenarios depicted in (A) and (B) could be considered to illustrate opposite ends of a spectrum.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
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Figure 8: Diagram of hypothetical Golgi cell innervation patterns in a glomerulus with a complex mossy fibre rosette. (A) In one possible scenario, Golgi cells (GoC) innervating the same glomerulus overlap in their axonal innervation territory, making a large glomerulus a functional entity. The global presynaptic inhibition of the rosette is due to summation of activity of all Golgi cells innervating the glomerulus. Control situation for (A) and (B) with no Golgi cell inhibition is indicated in Figure 7G. (B) In another scenario, no or marginal overlap of Golgi cell axons occur within a large glomerulus. Different compartments of a large complex rosette could in this way be subject to local presynaptic inhibition by different Golgi cell populations. This indicates that control of input to the cerebellar cortex could be more fine-grained than suggested by the scenario in (A), where an entire glomerulus functions as an input unit. Future anatomical analysis may allow to differentiate between these alternatives. In (B), the relative activity levels (indicated by the number and spacing of small vertical lines close to each cell) of Golgi cells may dynamically control presynaptic calcium influx in different branches of a rosette. Feedback as well as lateral-inhibition by Golgi cells could functionally compartmentalize the glomerulus. Note that the Golgi cells in the diagrams (A) and (B) represent two different cell populations and are not an indication of the actual number of Golgi cells innervating a glomerulus. Note also that the innervation scenarios depicted in (A) and (B) could be considered to illustrate opposite ends of a spectrum.
Mentions: If the axonal territories of Golgi cells do not overlap completely within a large complex glomerulus (Figure 8; cf. Figures 1 and 7), the restricted extracellular GABA diffusion within a glomerulus at physiological temperature (cf. Mitchell and Silver, 2000) opens the possibility that a large glomerulus may be functionally compartmentalized by local differences in extracellular GABA concentration, depending on the spatial activity pattern of Golgi cells. In this way, presynaptic inhibition by Golgi cell-mediated feedback- and lateral-inhibition to a particular glomerulus may finely regulate the mossy fibre input to specific granule cell subpopulations contacting this glomerulus (Figure 8). Evidence has previously been obtained in the cat that Golgi cell inhibition of separate mossy fibre inputs could be due to anatomically very specific distribution patterns of Golgi cell axons (Precht and Llinás, 1969), but it is presently not clear if this may be related to the scenario proposed in Figure 8. Compartmentalization of a glomerulus by Golgi cell activity (Figure 8B) may hypothetically lead to differential LTP/LTD induction (cf. Gall et al., 2005) at different mossy fibre-granule cell synapses in this glomerulus (cf. D'Angelo et al., 1999), due to spatially specific and varying degrees of Golgi cell-mediated inhibition (cf. Eccles et al., 1966; Precht and Llinás, 1969; Gabbiani et al., 1994) of voltage-dependent calcium influx in different granule cells belonging to the glomerulus. This would increase the cerebellar information storage capacity at the glomerular level compared to a scenario where each glomerulus functions as a unit. This hypothesis could be directly tested in future LTP/LTD-induction experiments by recording simultaneously from two granule cells belonging to the same glomerulus.

Bottom Line: A paired-pulse depression of the calcium signal lasting more than 1 s affected burst firing in mossy fibres; this paired-pulse depression was reduced by GABA B antagonists.While our results indicated that a presynaptic rosette electrophysiologically functioned as a unit, topical GABA application showed that calcium signals in the branches of complex rosettes could be modulated locally, suggesting that cerebellar glomeruli may be dynamically sub-compartmentalized due to ongoing inhibition mediated by Golgi cells.This could provide a fine-grained control of mossy fibre-granule cell information transfer and synaptic plasticity within a mossy fibre rosette.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen Copenhagen, Denmark.

ABSTRACT
Whole-cell recordings were obtained from mossy fibre terminals in adult turtles in order to characterize the basic membrane properties. Calcium imaging of presynaptic calcium signals was carried out in order to analyse calcium dynamics and presynaptic GABA B inhibition. A tetrodotoxin (TTX)-sensitive fast Na(+) spike faithfully followed repetitive depolarizing pulses with little change in spike duration or amplitude, while a strong outward rectification dominated responses to long-lasting depolarizations. High-threshold calcium spikes were uncovered following addition of potassium channel blockers. Calcium imaging using Calcium-Green dextran revealed a stimulus-evoked all-or-none TTX-sensitive calcium signal in simple and complex rosettes. All compartments of a complex rosette were activated during electrical activation of the mossy fibre, while individual simple and complex rosettes along an axon appeared to be isolated from one another in terms of calcium signalling. CGP55845 application showed that GABA B receptors mediated presynaptic inhibition of the calcium signal over the entire firing frequency range of mossy fibres. A paired-pulse depression of the calcium signal lasting more than 1 s affected burst firing in mossy fibres; this paired-pulse depression was reduced by GABA B antagonists. While our results indicated that a presynaptic rosette electrophysiologically functioned as a unit, topical GABA application showed that calcium signals in the branches of complex rosettes could be modulated locally, suggesting that cerebellar glomeruli may be dynamically sub-compartmentalized due to ongoing inhibition mediated by Golgi cells. This could provide a fine-grained control of mossy fibre-granule cell information transfer and synaptic plasticity within a mossy fibre rosette.

No MeSH data available.


Related in: MedlinePlus