Anxiety and hippocampal neuronal activity: Relationship and potential mechanisms

The hippocampus has been implicated in modulating anxiety. It interacts with a variety of brain regions, both cortical and subcortical areas regulating emotion and stress responses, including prefrontal cortex, amygdala, hypothalamus, and the nucleus accumbens, to adjust anxiety levels in response to a variety of stressful conditions. Growing evidence indicates that anxiety is associated with increased neuronal excitability in the hippocampus, and alterations in local regulation of hippocampal excitability have been suggested to underlie behavioral disruptions characteristic of certain anxiety disorders. Furthermore, studies have shown that some anxiolytics can treat anxiety by altering the excitability and plasticity of hippocampal neurons. Hence, identifying cellular and molecular mechanisms and neural circuits that regulate hippocampal excitability in anxiety may be beneficial for developing targeted interventions for treatment of anxiety disorders particularly for the treatment-resistant cases. We first briefly review a role of the hippocampus in fear. We then review the evidence indicating a relationship between the hippocampal activity and fear/anxiety and discuss some possible mechanisms underlying stress-induced hippocampal excitability and anxiety-related behavior.