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  • Review Article
  • Published:

Long-term synaptic plasticity in hippocampal interneurons

Nature Reviews Neuroscience volume 8, pages 687–699 (2007)Cite this article

Key Points

  • Hippocampal interneurons express at least two forms of activity-dependent long-term potentiation (LTP) at glutamatergic synapses.

  • One form ('Hebbian' LTP) depends on N-methyl-D-aspartate (NMDA) receptors and has similar induction and expression mechanisms to the LTP that takes place in pyramidal cells.

  • However, different Ca2+–calmodulin-dependent kinases (acting downstream from NMDA receptors) from those that mediate LTP induction in pryamidal cells mediate LTP induction in interneurons.

  • The other form of LTP ('anti-Hebbian' LTP) depends on Ca2+-permeable AMPA receptors, but not NMDA receptors. The voltage-dependent conductance of these receptors allows Ca2+ flow during negative membrane potentials but not during depolarisation. Metabotropic glutamate receptors also contribute to the induction of NMDA receptor-independent LTP.

  • Neither form of LTP spreads to afferent pathways that were inactive during induction. Because interneurons do not have profuse dendritic spines, this observation argues against an obligatory role for spines in preventing the spread of LTP.

  • Both forms of LTP have their counterparts in two complementary forms of long-term depression (LTD).

  • NMDA receptor-dependent LTP and LTD appear to be expressed postsynaptically. NMDA receptor-independent LTP and LTD appear to be expressed presynaptically.

  • Different forms of plasticity occur at distinct synapses in the hippocampus and greatly expand the computational capacity of hippocampal networks.

Abstract

Rapid memory formation relies, at least in part, on long-term potentiation (LTP) of excitatory synapses. Inhibitory interneurons of the hippocampus, which are essential for information processing, have recently been found to exhibit not one, but two forms of LTP. One form resembles LTP that occurs in pyramidal neurons, which depends on N-methyl-D-aspartate receptors and is triggered by coincident pre- and postsynaptic activity. The other depends on Ca2+ influx through glutamate receptors that preferentially open when the postsynaptic neuron is at rest. Here we review these contrasting forms of LTP and describe how they are mirrored by two forms of long-term depression. We further discuss how the remarkable plasticity of glutamatergic synapses on interneurons greatly enhances the computational capacity of the cortical microcircuit.

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Figure 1: The rectification of ionotropic glutamate receptors and Ca2+ influx at different types of glutamatergic synapse.
Figure 2: Long-term potentiation (LTP) and long-term depression (LTD) in the hippocampal formation.
Figure 3: Complementary forms of synaptic plasticity at different types of glutamatergic synapse.
Figure 4: The possible computational roles of long-term potentiation (LTP) in cortical interneurons.

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Acknowledgements

Work in the authors' laboratory that was relevant to this Review was supported by the Medical Research Council, the Wellcome Trust and the Academy of Finland.

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Authors and Affiliations

  1. Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, United Kingdom

    Dimitri M. Kullmann

  2. Department of Pharmacology, Oxford University, Mansfield Road, Oxford, OX1 3QT, United Kingdom

    Karri P. Lamsa

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Glossary

Long-term potentiation

(LTP). The activity-dependent strengthening of synaptic transmission (usually lasting longer than 30 minutes) that is widely thought to underlie certain forms of memory acquisition. LTP is commonly induced by brief, high-frequency (100 Hz) stimulation (tetanization) of presynaptic axons, or by pairing low-frequency (1–2 Hz) presynaptic stimulation with postsynaptic depolarization. LTP at some glutamatergic synapses on interneurons obeys different induction rules.

NMDA receptor

A type of ionotropic glutamate receptor that is characterized by its slow kinetics and strong permeability to calcium. Its name derives from the potent and specific agonist N-methyl-D-aspartate.

Long-term depression

The counterpart of LTP. It is defined as an activity-dependent weakening of synaptic strength.

Inhibitory interneuron

A GABA-releasing neuron in the brain that projects mainly to local target neurons.

Principal cell

A type of neuron that usually releases glutamate and that integrates multiple synaptic inputs and sends the resultant information out through axons that project to relatively remote structures. Principal cells account for 80–90% of neurons in the cortex.

Fast-spiking axo-axonic cell

An interneuron that forms characteristic 'cartridge' synapses on the initial segments of axons. They are also known as 'chandelier' cells.

Neurogliaform cell

An interneuron that forms a dense axonal and dendritic plexus. Its shape is reminiscent of that of astrocytic glial cells.

O-LM cell

An inteneuron that has its soma and dendrites in the stratum oriens, and that projects to the stratum lacunosum-moleculare.

Basket cell

An interneuron that innervates the perisomatic region of target neurons. The axonal arborization of basket cells often resembles a basket surrounding the target cell body.

Feedback–feedforward dichotomy

The idea that interneurons mediate either feedback or feedforward inhibition, depending on whether they are innervated by the axons of remote principal cells or by the recurrent collaterals of local principal cells, respectively.

Acute brain slice

An experimental preparation that consists of freshly isolated slabs of brain tissue maintained in a chamber that is supplied with oxygenated artificial cerebrospinal fluid. It allows synaptic and neuronal properties to be studied with electrophysiological, optical, pharmacological and biochemical methods.

Latency jitter

Information transmission in the brain can be degraded in several ways – latency jitter describes trial-to-trial variability in the initiation of a synaptic signal or action potential.

Theta band

The frequency range of the power spectrum of an electro-encephalograph that ranges from approximately 4Hz to 8 Hz.

Theta oscillation

A type of brain activity that is characterized by prominent theta-band neuronal and synaptic activity. It typically occurs during exploratory activity in freely moving rodents.

Gamma band

The 30–70 Hz range of the electroencephalograph power spectrum. It is associated with high-level information processing.

Sharp-wave ripple

A brief (approximately 100 ms) episode of high-frequency (>100 Hz) population activity.

AMPA receptor

An ionotropic glutamate receptor that is characterized by fast kinetics. Its name is derived from the potent and specific agonist α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid. AMPA receptors can be differentiated into Ca2+-permeable and Ca2+-impermeable subtypes.

Post-transcriptional editing

The processing that some mRNA transcripts (including those that encode some of the AMPA and kainate receptor subunits) undergo before splicing and translation. One form of post-transcriptional editing results in the substitution of an arginine (R) codon for a glutamine (Q) codon: a change that affects several biophysical properties.

Rectifying AMPA receptor

An AMPA receptor that has a conductance that decreases with depolarization, and thus deviates from Ohm's law.

Non-rectifying AMPA receptor

An AMPA receptor that contains an edited GluR2 subunit and has a voltage-independent conductance.

Mossy fibres

The axons of dentate granule cells. They project to the hilus of the dentate gyrus and to the CA3 region of the hippocampus proper. These axons have several unusual properties, including abundant presynaptic expression of the metabotropic glutamate receptor mGluR7, and the occurrence of giant boutons that synapse on CA3 pyramidal neurons. Mossy fibres also synapse with interneurons in the hippocampus.

Metabotropic glutamate receptors

A family of eight G-protein-coupled glutamate receptors that have a characteristic seven-transmembrane segment topology. They are grouped into three classes (I–III) depending on their pharmacological properties and their downstream metabolic cascades.

Tetanic stimulation

The high-frequency activation of axons evokes a postsynaptic signal in which the responses to individual presynaptic action potentials merge together (a tetanus) – such stimulation is said to be tetanic.

Whole-cell patch-clamp recording

A variation of the patch-clamp method whereby the membrane under the mouth of a pipette that has been applied to a neuron is ruptured, providing excellent electrical access to the neuron. The drawback of this technique is that cytoplasmic integrity is compromised.

Protracted recording period

When a whole-cell patch-clamp recording lasts longer than approximately 20 minutes, precluding LTP induction in pyramidal cells. In aspiny interneurons, the viable recording period before LTP induction is much shorter.

Perforated patch method

A variant of the cell-attached patch-clamp method in which the membrane under the mouth of the pipette is not ruptured, but instead an antibiotic (typically gramicidin, nystatin or amphotericin B) is included in the pipette solution to form ion-conducting pores. This allows good electrical access to the cell without compromising cytoplasmic integrity.

Aspiny dendrites

Dendrites that are devoid of spines or equipped with only sparse spines. Cortical inhibitory interneurons typically have aspiny dendrites.

Transient receptor potential channels

A family of ion channels that are related to voltage-gated potassium channels. Many are permeable to multiple cations and are opened in response to intracellular messengers.

Paired-pulse ratio

A measure of short-term, use-dependent synaptic plasticity that is obtained by dividing the response to the second of two stimuli by the response to the first stimulus. A presynaptic alteration in release probability is almost universally accompanied by a change in paired-pulse ratio.

Failure rate

The rate at which a synapse fails to release any neurotransmitter and hence to generate any postsynaptic response (action-potential-dependent neurotransmitter release is probabilistic). The failure rate gives an indirect indication of the state of the presynaptic release machinery.

Coefficient of variation of EPSCs

The standard deviation of action-potential-dependent EPSCs divided by their mean amplitude. This measure is used to describe the EPSCs' trial-to-trial amplitude fluctuation. An increase in transmitter release probability is typically associated with a decrease in the coefficient of variation.

Hebbian LTP

A type of long-term potentiation in which the induction rules approximate Hebb's postulate (the need for a conjunction of pre- and postsynaptic activity).

Asynchronous afferent volley

When multiple input axons fire independently of one another.

Place cells

Neurons that tend to fire when an animal is in a specific region of its spatial arena. Such behaviour is typical of hippocampal principal cells.

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Kullmann, D., Lamsa, K. Long-term synaptic plasticity in hippocampal interneurons. Nat Rev Neurosci 8, 687–699 (2007). https://doi.org/10.1038/nrn2207

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