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The enigmatic mossy cell of the dentate gyrus

Nature Reviews Neuroscience volume 17, pages 562–575 (2016)Cite this article

Subjects

Key Points

  • Mossy cells are a major subpopulation of dentate gyrus neurons with unique structure and physiological properties.

  • Deletion of both mossy cells and some of the pyramidal cells in area CA3 leads to a transient increase in excitability, anxiety and impaired contextual discrimination, suggesting that mossy cells have a role in excitability and behaviour.

  • Optogenetic activation of mossy cells primarily inhibits granule cells rather than exciting them, supporting the view that mossy cells primarily activate GABAergic interneurons that inhibit granule cells, at least in hippocampal slices.

  • Evidence suggests that mossy cells could also play a part in associative learning, pattern separation, conditional excitation of granule cells and novelty detection.

  • Mossy cells are vulnerable to neurotoxic insults, and damage to these cells may have an important role in the pathophysiology of neurological conditions and psychiatric illness.

  • The vulnerability of mossy cells may arise as a result of the strong input that they receive from granule cells, their pattern of gene expression, their subcellular metabolism and their physiological properties.

Abstract

Mossy cells comprise a large fraction of the cells in the hippocampal dentate gyrus, suggesting that their function in this region is important. They are vulnerable to ischaemia, traumatic brain injury and seizures, and their loss could contribute to dentate gyrus dysfunction in such conditions. Mossy cell function has been unclear because these cells innervate both glutamatergic and GABAergic neurons within the dentate gyrus, contributing to a complex circuitry. It has also been difficult to directly and selectively manipulate mossy cells to study their function. In light of the new data generated using methods to preferentially eliminate or activate mossy cells in mice, it is timely to ask whether mossy cells have become any less enigmatic than they were in the past.

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Figure 1: The organization of the dentate gyrus of rodents and primates.
Figure 2: The cell types of the dentate gyrus.
Figure 3: Organization of the mossy cell axon.
Figure 4: Possible roles of mossy cells in dentate gyrus function.

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Acknowledgements

This work is supported by the US National Institutes of Health, the Alzheimer's Association and the New York State Office of Mental Health.

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Authors and Affiliations

  1. Departments of Child and Adolescent Psychiatry, Physiology and Neuroscience, and Psychiatry, New York University Langone Medical Center, 10016, New York, USA

    Helen E. Scharfman

  2. Center for Dementia Research, The Nathan Kline Institute for Psychiatric Research, Orangeburg, 10962, New York, USA

    Helen E. Scharfman

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Glossary

Golgi technique

A method established by Camillo Golgi that stains many neurons almost completely (except for their axons) so they can be visualized in detail.

Optogenetics

The use of light to activate opsins (located in the plasma membrane), which open channels for cations or anions to flow. After opsins are expressed in one cell type, they can be activated selectively by light. Targeting opsins to specific cell types is done after identifying unique genes in the cell type, so the combination of light (opto-) and genetics (optogenetics) is fundamental to the approach.

Electron microscopy

The use of microscopes with very high (nanometre) resolution, made possible by accelerating the electrons through a specialized microscope. Electron microscopy can be used with very thin brain sections, allowing parts of neurons (such as synapses) to be detected.

Contextual fear conditioning

A behavioural test that examines the response to an environment or context after a prior exposure to the context and a painful stimulus.

Cre recombinase

(Cre). Part of a site-specific recombination system derived from Escherichia coli bacteriophage P1. Two short DNA sequences (loxP sites) are engineered to flank the target DNA. Activation of the Cre recombinase enzyme catalyses the recombination between the loxP sites, leading to excision of the intervening sequence.

Disinhibition

A decrease in inhibition (usually GABAergic). For example, blockade of the release of GABA from GABAergic neurons would result in a decrease in inhibition of the neuron that is postsynaptic to the GABAergic neuron.

Long-term potentiation

(LTP). A lasting increase in synaptic transmission. LTP is often elicited by a brief period of high-frequency presynaptic firing. However, other types of stimulation can elicit LTP, such as exposure to neuromodulators.

Field potentials

The changes in the extracellular potential that reflect changes in the flow of cations and anions in the extracellular space.

Retrograde signalling

The changes induced in a presynaptic terminal, usually mediated by a neuromodulator acting on its presynaptic receptors, which are evoked by release of the neuromodulator from the postsynaptic site.

Voltage imaging

The identification of neuronal activity by capturing changes in fluorescence that are proportional to changes in membrane potential. Typically, a voltage-sensitive dye is applied to the preparation of neurons so that voltage imaging can be conducted.

Electroencephalogram

(EEG). Recordings of the electrical activity of the brain with electrodes that are not inside the neurons (intracellular), but outside (extracellular) or remote (on the brain surface or skull).

Oscillations

The intermittent activity of neurons that is sufficiently synchronous to induce rhythmic fluctuations in the extracellular potential.

Recurrent collaterals

The branches of the axons of a population of neurons that innervate the dendrites of the same population of neurons. In area CA3, the pyramidal cells do not innervate their own dendrites but the dendrites of other CA3 pyramidal neurons.

Afterdepolarization

A depolarization occurring after an event, typically after an action potential.

Spike frequency adaptation

(SFA). A reduction in frequency of action potential discharge during a constant depolarizing input. Most neurons have a high firing frequency after the beginning of a strong depolarization, and the firing frequency decays if the depolarization continues.

Contextual discrimination

A behavioural task that tests the ability to distinguish two environments or contexts.

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Scharfman, H. The enigmatic mossy cell of the dentate gyrus. Nat Rev Neurosci 17, 562–575 (2016). https://doi.org/10.1038/nrn.2016.87

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