Reduced reactivity to novelty, impaired social behavior, and enhanced basal synaptic excitatory activity in perforant path projections to the dentate gyrus in young adult mice deficient in the neural cell adhesion molecule CHL1.
The neural cell adhesion molecule CHL1 is implicated in neural development in the mouse and has been related to psychiatric disorders in humans. Here we report that mice constitutively deficient for CHL1 display reduced reactivity to environmental stimuli and reduced expression of social behaviors, whereas cognitive, motor and olfactory functions are normal. Basal synaptic transmission and plasticity in seven major excitatory connections in the hippocampus were analyzed to test whether dysfunctions in this brain region, which controls complex behaviors, correlate with the behavioral alterations of CHL1 deficient mice. We found that basal synaptic transmission in lateral and medial perforant path projections to the dentate gyrus is elevated in CHL1-deficient mice. Taking in consideration the function of these synapses in processing information from cortical areas, we hypothesize that constitutive ablation of CHL1 leads to reduced capability to react to external stimuli due to dysfunctions in the dentate gyrus.
Morellini
Fabio
F
Zentrum für Molekulare Neurobiologie, Universitätsklinikum Eppendorf-Hamburg, Martinistrasse 52, D-20246 Hamburg, Germany.
Lepsveridze
Eka
E
Kähler
Birgit
B
Dityatev
Alexander
A
Schachner
Melitta
M
D000818:Animals; D001362:Avoidance Learning; D001522:Behavior, Animal; D015815:Cell Adhesion Molecules / Q000172:deficiency*; D018891:Dentate Gyrus / Q000502:physiology*; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics / Q000528:radiation effects; D005106:Exploratory Behavior / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000235:genetics / Q000528:radiation effects; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D019580:Perforant Pathway / Q000502:physiology*; D011930:Reaction Time / Q000235:genetics; D012920:Social Behavior Disorders / Q000235:genetics*; D009435:Synaptic Transmission / Q000235:genetics*
D015815:Cell Adhesion Molecules; C490649:Chl1 protein, mouse