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Sensory transmission in cerebellar granule cells relies on similarly coded mossy fiber inputs.

ABSTRACT: The computational principles underlying the processing of sensory-evoked synaptic inputs are understood only rudimentarily. A critical missing factor is knowledge of the activation patterns of the synaptic inputs to the processing neurons. Here we use well-defined, reproducible skin stimulation to describe the specific signal transformations that occur in different parallel mossy fiber pathways and analyze their representation in the synaptic inputs to cerebellar granule cells. We find that mossy fiber input codes are preserved in the synaptic responses of granule cells, suggesting a coding-specific innervation. The computational consequences of this are that it becomes possible for granule cells to also transmit weak sensory inputs in a graded fashion and to preserve the specific activity patterns of the mossy fibers.

SUBMITTER: Bengtsson F

PROVIDER: S-EPMC2650166 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Sensory transmission in cerebellar granule cells relies on similarly coded mossy fiber inputs.

Bengtsson Fredrik F Jörntell Henrik H

Proceedings of the National Academy of Sciences of the United States of America 20090121 7

The computational principles underlying the processing of sensory-evoked synaptic inputs are understood only rudimentarily. A critical missing factor is knowledge of the activation patterns of the synaptic inputs to the processing neurons. Here we use well-defined, reproducible skin stimulation to describe the specific signal transformations that occur in different parallel mossy fiber pathways and analyze their representation in the synaptic inputs to cerebellar granule cells. We find that moss ...[more]

PMID: 19164536

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Project description:Epileptic seizures potently modulate hippocampal adult neurogenesis, and adult-born dentate granule cells contribute to the pathologic retrograde sprouting of mossy fiber axons, both hallmarks of temporal lobe epilepsy. The characteristics of these sprouted synapses, however, have been largely unexplored, and the specific contribution of adult-born granule cells to functional mossy fiber sprouting is unknown, primarily due to technical barriers in isolating sprouted mossy fiber synapses for analysis. Here, we used DcxCreERT2 transgenic mice to permanently pulse-label age-defined cohorts of granule cells born either before or after pilocarpine-induced status epilepticus (SE). Using optogenetics, we demonstrate that adult-born granule cells born before SE form functional recurrent monosynaptic excitatory connections with other granule cells. Surprisingly, however, although healthy mossy fiber synapses in CA3 are well characterized "detonator" synapses that potently drive postsynaptic cell firing through their profound frequency-dependent facilitation, sprouted mossy fiber synapses from adult-born cells exhibited profound frequency-dependent depression, despite possessing some of the morphological hallmarks of mossy fiber terminals. Mature granule cells also contributed to functional mossy fiber sprouting, but exhibited less synaptic depression. Interestingly, granule cells born shortly after SE did not form functional excitatory synapses, despite robust sprouting. Our results suggest that, although sprouted mossy fibers form recurrent excitatory circuits with some of the morphological characteristics of typical mossy fiber terminals, the functional characteristics of sprouted synapses would limit the contribution of adult-born granule cells to hippocampal hyperexcitability in the epileptic hippocampus.SIGNIFICANCE STATEMENT In the hippocampal dentate gyrus, seizures drive retrograde sprouting of granule cell mossy fiber axons. We directly activated sprouted mossy fiber synapses from adult-born granule cells to study their synaptic properties. We reveal that sprouted synapses from adult-born granule cells have a diminished ability to sustain recurrent excitation in the epileptic hippocampus, which raises questions about the role of sprouting and adult neurogenesis in sustaining seizure-like activity.

Dataset Information

Sensory transmission in cerebellar granule cells relies on similarly coded mossy fiber inputs.

Publications

Sensory transmission in cerebellar granule cells relies on similarly coded mossy fiber inputs.

Similar Datasets

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