ABSTRACT
Background
Maintaining gamma-aminobutyric acidergic (GABAergic) inhibition in the amygdala within
a physiological range is critical for the appropriate expression of emotions such
as fear and anxiety. The synaptic GABA type A receptor (GABAAR) is generally known to mediate the primary component of amygdala inhibition and
prevent inappropriate expression of fear. However, little is known about the contribution
of the extrasynaptic GABAAR to amygdala inhibition and fear.
Methods
By using mice expressing green fluorescent protein in interneurons (INs) and lacking
the δ subunit-containing GABAAR (GABAA(δ)R), which is exclusively situated in the extrasynaptic membrane, we systematically
investigated the role of GABAA(δ)R in regulating inhibition in the lateral amygdala (LA) and fear learning using
the combined approaches of immunohistochemistry, electrophysiology, and behavior.
Results
In sharp contrast to the established role of synaptic GABAAR in mediating LA inhibition, we found that either pharmacological or physiological
recruitment of GABAA(δ)R resulted in the weakening of GABAergic transmission onto projection neurons in
LA while leaving the glutamatergic transmission unaltered, suggesting disinhibition
by GABAA(δ)R. The disinhibition arose from IN-specific expression of GABAA(δ)R with its activation decreasing the input resistance of local INs and suppressing
their activation. Genetic deletion of GABAA(δ)R attenuated its role in suppressing LA INs and disinhibiting LA. Importantly,
the GABAA(δ)R facilitated long-term potentiation in sensory afferents to LA and permitted the
expression of learned fear.
Conclusions
Our findings suggest that GABAA(δ)R serves as a brake rather than a mediator of GABAergic inhibition in LA. The disinhibition
by GABAA(δ)R may help to prevent excessive suppression of amygdala activity and thus ensure
the expression of emotion.
Keywords
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Article info
Publication history
Published online: July 06, 2016
Accepted:
June 24,
2016
Received in revised form:
June 7,
2016
Received:
March 15,
2016
Identification
Copyright
© Society of Biological Psychiatry, 2016.
