Complementary δ2-protocadherin expression delineates parallel basal ganglia circuits in primates

Area of Science:

• Neuroscience
• Molecular Biology
• Cell Adhesion

Background:

• The basal ganglia (BG) comprise parallel circuits crucial for motor control and cognition.
• The molecular mechanisms that establish segregated yet integrated functional territories within the BG remain largely unknown.
• Cell adhesion molecules, such as protocadherins, are implicated in neuronal circuit formation.

Purpose of the Study:

• To investigate the expression patterns of three δ2-protocadherin (δ2-PCDH) cell adhesion molecules (PCDH10, PCDH17, PCDH19) in the primate basal ganglia.
• To determine if these δ2-PCDHs contribute to the molecular specification of functional territories within the BG circuits.

Main Methods:

• Immunohistochemical mapping of PCDH10, PCDH17, and PCDH19 expression in macaque basal ganglia.
• Analysis of expression gradients along rostro-caudal and ventromedial-dorsolateral axes within the striatum and BG output nuclei.

Main Results:

• Each of the three δ2-PCDHs exhibited distinct regional gradients of expression within the striatum.
• The expression patterns of PCDH10, PCDH17, and PCDH19 were complementary, delineating molecular boundaries that correspond to functional BG subdivisions.
• Similar complementary distributions were observed in the BG output nuclei.

Conclusions:

• The complementary expression patterns of PCDH10, PCDH17, and PCDH19 align with distinct BG circuits.
• These findings suggest that δ2-PCDHs act as molecular codes specifying functional territories within the parallel circuits of the primate basal ganglia.
• This provides insight into the molecular mechanisms underlying the segregated yet integrative organization of the BG.