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In vivo differences in inputs and spiking between neurons in lobules VI/VII of neocerebellum and lobule X of archaeocerebellum.

Witter L, De Zeeuw CI - Cerebellum (2015)

Bottom Line: Using whole-cell and cell-attached recordings in vivo in anesthetized mice, we show that the mossy fiber inputs to these functionally distinct areas of the cerebellum differ in that the irregularity and bursty character of their firing is significantly greater in lobules VI/VII than in lobule X.Importantly, this difference in mossy fiber regularity is propagated through the granule cells at the input stage to the Purkinje cells and molecular layer interneurons, ultimately resulting in different regularity of simple spikes.These data show that the firing behavior of cerebellar cortical neurons does not only reflect particular intrinsic properties but also an interesting interplay with the innate activity at the input stage.

View Article: PubMed Central - PubMed

Affiliation: Netherlands Institute for Neuroscience, Royal Academy for Arts and Sciences (KNAW), Meibergdreef 47, 1105 BA, Amsterdam, The Netherlands.

ABSTRACT
The cerebellum plays an important role in the coordination and refinement of movements and cognitive processes. Recently, it has been shown that the main output neuron of the cerebellar cortex, i.e., the Purkinje cell, can show a different firing behavior dependent on its intrinsic electrophysiological properties. Yet, to what extent a different nature of mossy fiber inputs can influence the firing behavior of cerebellar cortical neurons remains to be elucidated. Here, we compared the firing rate and regularity of mossy fibers and neurons in two different regions of cerebellar cortex. One region intimately connected with the cerebral cortex, i.e., lobules VI/VII of the neocerebellum, and another one strongly connected with the vestibular apparatus, i.e., lobule X of the archaeocerebellum. Given their connections, we hypothesized that activity in neurons in lobules VI/VII and lobule X may be expected to be more phasic and tonic, respectively. Using whole-cell and cell-attached recordings in vivo in anesthetized mice, we show that the mossy fiber inputs to these functionally distinct areas of the cerebellum differ in that the irregularity and bursty character of their firing is significantly greater in lobules VI/VII than in lobule X. Importantly, this difference in mossy fiber regularity is propagated through the granule cells at the input stage to the Purkinje cells and molecular layer interneurons, ultimately resulting in different regularity of simple spikes. These data show that the firing behavior of cerebellar cortical neurons does not only reflect particular intrinsic properties but also an interesting interplay with the innate activity at the input stage.

No MeSH data available.


Molecular layer interneurons. a Two examples of spiking activity of molecular layer interneurons in lobules VI/VII (left) and lobule X (right). b Histograms of interspike intervals for all cells (thin lines) for both lobules VI/VII (green) and lobule X (blue). Thick lines indicate the average interspike interval distributions. c Boxplots of spiking activity of molecular layer interneurons. d Firing rate adaptation over a 1,000 ms current input. Each bin represents the normalized (to bin 1) number of spikes fired in 50 ms. Error bars indicate ± SEM
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Fig4: Molecular layer interneurons. a Two examples of spiking activity of molecular layer interneurons in lobules VI/VII (left) and lobule X (right). b Histograms of interspike intervals for all cells (thin lines) for both lobules VI/VII (green) and lobule X (blue). Thick lines indicate the average interspike interval distributions. c Boxplots of spiking activity of molecular layer interneurons. d Firing rate adaptation over a 1,000 ms current input. Each bin represents the normalized (to bin 1) number of spikes fired in 50 ms. Error bars indicate ± SEM

Mentions: Purkinje cell activity is regulated not only by granule cell input but also by molecular layer interneurons, which provide a feed-forward inhibition from granule cells onto Purkinje cells [16, 26]. Additionally, molecular layer interneurons receive spill-over climbing fiber input and sense extracellular calcium to provide feed-forward inhibition in response to climbing fiber input and synaptic activity, in general [27–29]. To further evaluate the output of granule cells and its possible impact on Purkinje cells, we recorded from molecular layer interneurons, which are electrically more compact than Purkinje cells and thus provide an opportunity to record granule cell output in the form of EPSPs. We recorded the activity of 32 molecular layer interneurons from lobules VI/VII (N = 12) and lobule X (N = 20) in anesthetized mice. Molecular layer interneurons were characterized by low membrane resistance (144.3 ± 90.6 MΩ) and intermediate membrane time constants (3.8 ± 3.1 ms; Table 1). Irrespective of their location in lobules VI/VII or lobule X, the molecular layer interneurons all received spontaneous excitatory synaptic inputs. Due to the low amplitude and high frequency of synaptic inputs, it was impossible to reliably identify separate events (Fig. 4a). Given that most of the granule cells were silent in our preparation (see above), these findings imply that molecular layer interneurons probably receive input from a large population of granule cells [9, 30]. Although we could not reliably analyze individual EPSPs, we observed that molecular layer interneurons recorded from lobules VI/VII received excitatory inputs arriving in bursts, whereas those in lobule X occurred in a tonic fashion (Fig. 4a). Indeed, when comparing the regularity of molecular layer interneuron spiking to mossy fiber inputs to granule cells, we observed that spiking in lobules VI/VII interneurons was more irregular than that in lobule X; this held especially true at the shorter time scales (CV 1.15 ± 0.33 vs. 0.98 ± 0.54, p = 0.36; CV2 0.93 ± 0.15 vs. 0.64 ± 0.19, p = 0.001; Fig. 4b). Together, these data indicate that the level of regularity of mossy fiber inputs to granule cells is probably largely conserved in the output of the granule cells.Fig. 4


In vivo differences in inputs and spiking between neurons in lobules VI/VII of neocerebellum and lobule X of archaeocerebellum.

Witter L, De Zeeuw CI - Cerebellum (2015)

Molecular layer interneurons. a Two examples of spiking activity of molecular layer interneurons in lobules VI/VII (left) and lobule X (right). b Histograms of interspike intervals for all cells (thin lines) for both lobules VI/VII (green) and lobule X (blue). Thick lines indicate the average interspike interval distributions. c Boxplots of spiking activity of molecular layer interneurons. d Firing rate adaptation over a 1,000 ms current input. Each bin represents the normalized (to bin 1) number of spikes fired in 50 ms. Error bars indicate ± SEM
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig4: Molecular layer interneurons. a Two examples of spiking activity of molecular layer interneurons in lobules VI/VII (left) and lobule X (right). b Histograms of interspike intervals for all cells (thin lines) for both lobules VI/VII (green) and lobule X (blue). Thick lines indicate the average interspike interval distributions. c Boxplots of spiking activity of molecular layer interneurons. d Firing rate adaptation over a 1,000 ms current input. Each bin represents the normalized (to bin 1) number of spikes fired in 50 ms. Error bars indicate ± SEM
Mentions: Purkinje cell activity is regulated not only by granule cell input but also by molecular layer interneurons, which provide a feed-forward inhibition from granule cells onto Purkinje cells [16, 26]. Additionally, molecular layer interneurons receive spill-over climbing fiber input and sense extracellular calcium to provide feed-forward inhibition in response to climbing fiber input and synaptic activity, in general [27–29]. To further evaluate the output of granule cells and its possible impact on Purkinje cells, we recorded from molecular layer interneurons, which are electrically more compact than Purkinje cells and thus provide an opportunity to record granule cell output in the form of EPSPs. We recorded the activity of 32 molecular layer interneurons from lobules VI/VII (N = 12) and lobule X (N = 20) in anesthetized mice. Molecular layer interneurons were characterized by low membrane resistance (144.3 ± 90.6 MΩ) and intermediate membrane time constants (3.8 ± 3.1 ms; Table 1). Irrespective of their location in lobules VI/VII or lobule X, the molecular layer interneurons all received spontaneous excitatory synaptic inputs. Due to the low amplitude and high frequency of synaptic inputs, it was impossible to reliably identify separate events (Fig. 4a). Given that most of the granule cells were silent in our preparation (see above), these findings imply that molecular layer interneurons probably receive input from a large population of granule cells [9, 30]. Although we could not reliably analyze individual EPSPs, we observed that molecular layer interneurons recorded from lobules VI/VII received excitatory inputs arriving in bursts, whereas those in lobule X occurred in a tonic fashion (Fig. 4a). Indeed, when comparing the regularity of molecular layer interneuron spiking to mossy fiber inputs to granule cells, we observed that spiking in lobules VI/VII interneurons was more irregular than that in lobule X; this held especially true at the shorter time scales (CV 1.15 ± 0.33 vs. 0.98 ± 0.54, p = 0.36; CV2 0.93 ± 0.15 vs. 0.64 ± 0.19, p = 0.001; Fig. 4b). Together, these data indicate that the level of regularity of mossy fiber inputs to granule cells is probably largely conserved in the output of the granule cells.Fig. 4

Bottom Line: Using whole-cell and cell-attached recordings in vivo in anesthetized mice, we show that the mossy fiber inputs to these functionally distinct areas of the cerebellum differ in that the irregularity and bursty character of their firing is significantly greater in lobules VI/VII than in lobule X.Importantly, this difference in mossy fiber regularity is propagated through the granule cells at the input stage to the Purkinje cells and molecular layer interneurons, ultimately resulting in different regularity of simple spikes.These data show that the firing behavior of cerebellar cortical neurons does not only reflect particular intrinsic properties but also an interesting interplay with the innate activity at the input stage.

View Article: PubMed Central - PubMed

Affiliation: Netherlands Institute for Neuroscience, Royal Academy for Arts and Sciences (KNAW), Meibergdreef 47, 1105 BA, Amsterdam, The Netherlands.

ABSTRACT
The cerebellum plays an important role in the coordination and refinement of movements and cognitive processes. Recently, it has been shown that the main output neuron of the cerebellar cortex, i.e., the Purkinje cell, can show a different firing behavior dependent on its intrinsic electrophysiological properties. Yet, to what extent a different nature of mossy fiber inputs can influence the firing behavior of cerebellar cortical neurons remains to be elucidated. Here, we compared the firing rate and regularity of mossy fibers and neurons in two different regions of cerebellar cortex. One region intimately connected with the cerebral cortex, i.e., lobules VI/VII of the neocerebellum, and another one strongly connected with the vestibular apparatus, i.e., lobule X of the archaeocerebellum. Given their connections, we hypothesized that activity in neurons in lobules VI/VII and lobule X may be expected to be more phasic and tonic, respectively. Using whole-cell and cell-attached recordings in vivo in anesthetized mice, we show that the mossy fiber inputs to these functionally distinct areas of the cerebellum differ in that the irregularity and bursty character of their firing is significantly greater in lobules VI/VII than in lobule X. Importantly, this difference in mossy fiber regularity is propagated through the granule cells at the input stage to the Purkinje cells and molecular layer interneurons, ultimately resulting in different regularity of simple spikes. These data show that the firing behavior of cerebellar cortical neurons does not only reflect particular intrinsic properties but also an interesting interplay with the innate activity at the input stage.

No MeSH data available.