Subgenual and Hippocampal Pathways in Amygdala Are Set to Balance Affect and Context Processing

Area of Science:

• Neuroscience
• Cognitive Neuroscience
• Cellular Neuroscience

Background:

• The amygdala, hippocampus, and subgenual cortex area 25 (A25) are crucial for cognitive-emotional processing.
• Understanding the specific neural pathways and synaptic interactions between these regions is essential for deciphering complex behaviors and emotional regulation.

Purpose of the Study:

• To investigate the anatomical and microcircuit-level interactions between the hippocampus and A25 with postsynaptic sites in the amygdala.
• To elucidate how these pathways interface with excitatory and inhibitory microcircuits within the amygdala.

Main Methods:

• Neural tracing techniques in rhesus monkeys of both sexes.
• High-resolution confocal and electron microscopy (EM) to analyze synaptic connections.
• Identification of postsynaptic targets within amygdalar nuclei, including specific interneuron populations.

Main Results:

• Both hippocampus and A25 innervate distinct and overlapping regions of the basolateral (BL) amygdalar nucleus.
• Hippocampal pathways preferentially target the paralaminar nucleus (plasticity) and calbindin (CB) inhibitory neurons (contextual learning).
• A25 pathways preferentially target intercalated masses (inhibitory control) and parvalbumin (PV) inhibitory neurons (flexible gain regulation), and calretinin (CR) neurons (disinhibition).

Conclusions:

• Common and unique innervation patterns by hippocampus and A25 in the amygdala suggest differential roles in cognitive-emotional processing.
• Preferential innervation of disinhibitory neurons (CR) by both pathways indicates a potential boost in amygdalar excitation.
• Divergent targeting of specific inhibitory interneurons (PV, CB) by A25 and hippocampus highlights circuit-specific mechanisms that may be disrupted in psychiatric disorders.