Molecular diversity of clustered protocadherin-α required for sensory integration and short-term memory in mice

• Published in: Scientific reports Vol. 8; no. 1; pp. 9616 - 10
• Main Authors: Yamagishi, Tatsuya, Yoshitake, Kohei, Kamatani, Daiki, Watanabe, Kenji, Tsukano, Hiroaki, Hishida, Ryuichi, Takahashi, Kuniyuki, Takahashi, Sugata, Horii, Arata, Yagi, Takeshi, Shibuki, Katsuei
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25-06-2018; Nature Publishing Group; Nature Portfolio
• Subjects: 59; 631/378/1595/1637; 631/378/2649/1723; 64/60; Associative learning; Cell adhesion & migration; Cell adhesion molecules; Cortex (somatosensory); Humanities and Social Sciences; Isoforms; multidisciplinary; Neural networks; Protocadherin; Science; Science (multidisciplinary); Sensory integration; Short term; Short term memory; Visual cortex; Visual discrimination learning; Visual pathways
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-28034-4

Clustered protocadherins (Pcdhs) are neuronal cell adhesion molecules characterized by homophilic adhesion between the tetramers of 58 distinct isoforms in mice. The diversity of Pcdhs and resulting highly-specific neuronal adhesion may be required for the formation of neural circuits for executing higher brain functions. However, this hypothesis remains to be tested, because knockout of
Pcdh
genes produces abnormalities that may interfere with higher brain functions indirectly. In
Pcdh-α1
,
12
mice, only α1, α12 and two constitutive isoforms are expressed out of 14 isoforms. The appearance and behavior of
Pcdh-α1
,
12
mice are similar to those of wild-type mice, and most abnormalities reported in
Pcdh-α
knockout mice are not present in
Pcdh-α1
,
12
mice. We examined
Pcdh-α1
,
12
mice in detail, and found that cortical depression induced by sensory mismatches between vision and whisker sensation in the visual cortex was impaired. Since Pcdh-α is densely distributed over the cerebral cortex, various types of higher function are likely impaired in
Pcdh-α1
,
12
mice. As expected, visual short-term memory of space/shape was impaired in behavioral experiments using space/shape cues. Furthermore, behavioral learning based on audio-visual associative memory was also impaired. These results indicate that the molecular diversity of Pcdh-α plays essential roles for sensory integration and short-term memory.