Directing negative emotional states through parallel genetically-distinct basolateral amygdala pathways to ventral striatum subregions

Area of Science:

• Neuroscience
• Molecular Biology
• Behavioral Science

Background:

• The basolateral amygdala (BLA) comprises diverse cell populations crucial for emotional regulation and anxiety disorders.
• Excitatory BLA neurons include two main classes, one expressing Ppp1r1b, downstream of dopamine receptors Drd1 and Drd2.
• The specific roles of Drd1+ and Drd2+ BLA neurons in emotional responses remain largely unexplored.

Purpose of the Study:

• To investigate the function of Drd1+ and Drd2+ BLA neuron populations in emotional processing.
• To elucidate the projection pathways and connectivity of these distinct neuronal populations within the ventral striatum.
• To determine how activation or suppression of these pathways influences learned and unlearned emotional behaviors.

Main Methods:

• Utilized genetic markers to identify and differentiate Drd1+ and Drd2+ BLA neuron populations.
• Traced neuronal projections from the basal nucleus of the BLA to the ventral striatum.
• Employed behavioral assays to assess the impact of modulating Drd1+ and Drd2+ pathways on emotional states.

Main Results:

• Identified Drd1+ and Drd2+ BLA neurons as forming two parallel pathways to the ventral striatum.
• Demonstrated that these pathways innervate the ventral striatum and excite its neurons.
• Showcased distinct influences of Drd1+ and Drd2+ pathways on learned and unlearned emotional states, dependent on projection targets and pathway activity.

Conclusions:

• Established parallel, genetically distinct BLA to ventral striatum circuits that modulate emotional states.
• Highlighted the projection-specific roles of Drd1+ and Drd2+ BLA neurons in regulating negative emotional states.
• Provided insights into the neural circuitry underlying emotional regulation and potential therapeutic targets for anxiety disorders.