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Diversity and function of corticopetal and corticofugal GABAergic projection neurons

Abstract

It is still widely thought that cortical projections to distant brain areas derive by and large from glutamatergic neurons. However, an increasing number of reports provide evidence that cortical GABAergic neurons comprise a smaller population of ‘projection neurons’ in addition to the well-known and much-studied interneurons. GABAergic long-range axons that derive from, or project to, cortical areas are thought to entrain distant brain areas for efficient information transfer and processing. Research conducted over the past 10 years has revealed that cortical GABAergic projection neurons are highly diverse in terms of molecular marker expression, synaptic targeting (identity of targeted cell types), activity pattern during distinct behavioural states and precise temporal recruitment relative to ongoing neuronal network oscillations. As GABAergic projection neurons connect many cortical areas unidirectionally or bidirectionally, it is safe to assume that they participate in the modulation of a whole series of behavioural and cognitive functions. We expect future research to examine how long-range GABAergic projections fine-tune activity in distinct distant networks and how their recruitment alters the behaviours that are supported by these networks.

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Fig. 1: GABAergic projection neurons form classical and atypical synapses.
Fig. 2: Cortical GABAergic projections.
Fig. 3: Oscillatory coupling of rhythmically firing hippocampal and septal GABAergic projection neurons.
Fig. 4: Target specificity of septo–hippocampal GABAergic neurons.

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Supplementary information

Glossary

Disinhibition

The release of inhibition from a neuron by the inhibition of inhibitory neurons; usually leads to increased excitability of the disinhibited neuron.

Tonic

This refers here to currents that are relatively long lasting and emerge through the opening of extrasynaptic receptors.

Theta oscillations

Oscillations of extracellularly recorded currents in the hippocampus at frequencies between 5 and 12 Hz; this rhythmic activity is most prominent during exploratory behaviour.

Grid cells

Neurons in the medial entorhinal cortex that are spatially tuned and whose hexagonal firing pattern accounts for the naming of this cell type; they support spatial memory and navigation.

Sharp wave–ripples

(SWRs). SWRs are extracellularly recorded, high frequency (150–250 Hz) synaptic currents that emerge through the highly synchronous firing of neurons in the hippocampus during immobility and slow wave sleep.

Phase coupling

Temporal alignment of the phases of two oscillators such that the first oscillator coincides with a fixed phase of the second oscillator.

Long-term potentiation

(LTP). Long-term potentiation is a form of plasticity reflecting long-lasting increases in synaptic strength.

Progenitor cells

Descendants from stem cells that have the ability to divide and differentiate but with a more limited differentiation potential than stem cells.

Stem cell quiescence

The state of a stem cell in which it does not divide but can be re-activated by external cues.

Long-term depression

Long-term depression is a form of plasticity reflecting long-lasting decreases in synaptic strength.

Schaffer collateral

An excitatory pathway from the CA3 area to the CA1 area of the hippocampus that undergoes plasticity and is thought to underlie certain forms of memory formation in the hippocampus.

AAV2-retro

A designed variant of recombinant adeno-associated viruses that allows the virus to be efficiently retrogradely transported from the axon terminal to the neuronal cell body.

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Melzer, S., Monyer, H. Diversity and function of corticopetal and corticofugal GABAergic projection neurons. Nat Rev Neurosci 21, 499–515 (2020). https://doi.org/10.1038/s41583-020-0344-9

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