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Preserving the balance: diverse forms of long-term GABAergic synaptic plasticity


Cellular mechanisms that regulate the interplay of synaptic excitation and inhibition are thought to be central to the functional stability of healthy neuronal circuits. A growing body of literature demonstrates the capacity for inhibitory GABAergic synapses to exhibit long-term plasticity in response to changes in neuronal activity. Here, we review this expanding field of research, focusing on the diversity of mechanisms that link glutamatergic signalling, postsynaptic action potentials and inhibitory synaptic strength. Several lines of evidence indicate that multiple, parallel forms of plasticity serve to regulate activity at both the input and output domains of individual neurons. Overall, these varied phenomena serve to promote both stability and flexibility over the life of the organism.

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The authors thank members of the Higley laboratory, J. Cardin, E. Petrini and T. Ravasenga, for critical reading and fruitful discussions during the preparation of this manuscript.

Reviewer information

Nature Reviews Neuroscience thanks B. Rudy and A. Sebastião for their contribution to the peer review of this work.

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All authors contributed equally to all aspects of the manuscript.

Competing interests

The authors declare no competing interests.

Correspondence to Michael J. Higley.


Organotypic cultures

Cell culture systems prepared from slices of neonatal or early postnatal brain, in which the general synaptic and circuit architecture is preserved.

Tonic inhibition

An inhibitory signal that is thought to utilize extrasynaptic receptors (not directly apposed to presynaptic release sites), may be decoupled from presynaptic spiking and occurs over long (minutes or more) periods.

Phasic inhibition

An inhibitory signal that relies on postsynaptic receptors closely apposed to presynaptic release sites, is typically coupled to presynaptic action potentials and is brief (tens to hundreds of milliseconds) in duration.

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Fig. 1: Schematic view of inhibitory inputs targeting different regions of a postsynaptic neuron.
Fig. 2: Schematic representation of the molecular components involved in the structure and regulation of ionotropic GABAergic synapses.