Frontostriatal Projections Regulate Innate Avoidance Behavior.

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Anxiety Disorders Research

Background:

• The dorsomedial prefrontal cortex (dmPFC) is implicated in decision-making and avoidance, processes altered in anxiety disorders.
• Previous research focused on the dmPFC-amygdala pathway for fear, but the specific circuits controlling anxious avoidance remain unclear.
• The striatum is increasingly recognized as a key hub for regulating avoidance behaviors.

Purpose of the Study:

• To identify specific top-down prefrontal projections involved in regulating avoidance behavior.
• To elucidate the neural mechanisms by which the dmPFC controls anxious avoidance.
• To differentiate the roles of dmPFC projections to the amygdala versus the striatum in defensive behaviors.

Main Methods:

• Utilized fiber photometry in male and female mice during the elevated zero maze task to record neural activity.
• Employed optogenetics to manipulate specific dmPFC projection pathways.
• Investigated the postsynaptic targets of dmPFC projections in the dorsomedial striatum (DMS), specifically D1 receptor-expressing neurons.

Main Results:

• Neural activity was heightened in dmPFC-striatal projection neurons, but not dmPFC-amygdala neurons, during exploration of anxiogenic environments.
• Optogenetic activation of the dmPFC-striatal pathway causally controlled innate avoidance behavior.
• This frontostriatal projection was found to preferentially excite D1 receptor-expressing neurons in the DMS.

Conclusions:

• The dmPFC-striatum projection, rather than the dmPFC-amygdala projection, is critical for controlling anxious avoidance behavior.
• This study supports a model where distinct dmPFC circuits mediate reflexive fear (amygdala) versus anxious avoidance (striatum).
• Identification of this specific corticostriatal circuit provides a mechanistic understanding of avoidance and potential targets for anxiety disorder treatments.