Inhibition in the amygdala anxiety circuitry

Abstract

Inhibitory neurotransmission plays a key role in anxiety disorders, as evidenced by the anxiolytic effect of the benzodiazepine class of γ-aminobutyric acid (GABA) receptor agonists and the recent discovery of anxiety-associated variants in the molecular components of inhibitory synapses. Accordingly, substantial interest has focused on understanding how inhibitory neurons and synapses contribute to the circuitry underlying adaptive and pathological anxiety behaviors. A key element of the anxiety circuitry is the amygdala, which integrates information from cortical and thalamic sensory inputs to generate fear and anxiety-related behavioral outputs. Information processing within the amygdala is heavily dependent on inhibitory control, although the specific mechanisms by which amygdala GABAergic neurons and synapses regulate anxiety-related behaviors are only beginning to be uncovered. Here, we summarize the current state of knowledge and highlight open questions regarding the role of inhibition in the amygdala anxiety circuitry. We discuss the inhibitory neuron subtypes that contribute to the processing of anxiety information in the basolateral and central amygdala, as well as the molecular determinants, such as GABA receptors and synapse organizer proteins, that shape inhibitory synaptic transmission within the anxiety circuitry. Finally, we conclude with an overview of current and future approaches for converting this knowledge into successful treatment strategies for anxiety disorders. Understanding inhibitory neurotransmission in the amygdala is key to developing more effective therapeutics against anxiety. Anxiety disorders are the most prevalent group of psychiatric diseases, yet they are often under-treated due to the limited efficacy and tolerability of current treatment approaches. Dilja Krueger-Burg and colleagues at the Max Planck Institute of Experimental Medicine in Göttingen, Germany, review current knowledge of the inhibitory neuronal circuits and molecular mechanisms that contribute to anxiety behaviors in the amygdala, a key brain region for processing emotions. It is well established that alterations in inhibitory neurotransmission and excessive excitatory neurotransmission underlie anxiety disorders. Using the latest technologies to identify the neuronal populations and synaptic components implicated in the regulation of anxiety-related behaviors should help to develop new targeted treatments with fewer side-effects.