Fig. 5

Postnatal development of CCK+ interneurons is impaired in the hippocampus of Dag1^cKO mice. (a) Timeline of interneuron developmental milestones including interneuron migration, cell death, and inhibitory synapse formation. (b-c) Immunostaining for CB₁R (green) in the hippocampus of Dag1^Control mice (b) shows a progressive increase in CCK+ interneuron axon terminals from P3-P15. In contrast, CB₁R+ axon terminals are diminished at all ages in Dag1^cKO mice (c). Asterisks (P3 and P5) denote the presence of CB₁R immunoreactivity in pyramidal neuron axons at early postnatal ages. Yellow boxes (b, c) indicate approximate locations of high magnification images in (d-e). High magnification (20X), single channel images (gray) of CB₁R+ axon terminals in the CA1 of Dag1^Control (d) and Dag1^cKO mice (e) from P3–15 months. Dotted white lines indicate the position of the pyramidal cell layer (SP). SO, stratum oriens; SP, stratum pyramidale; SR, stratum radiatum. f Quantification of CB₁R pixels in hippocampal CA1 layers from Dag1^Control (gray) and Dag1^cKO (pink) mice shows significantly reduced CB₁R staining at all ages examined (*P < 0.05, unpaired two-tailed Student’s t-test; n = 3–4 mice/genotype). Data are presented as mean values ± s.e.m. Data are normalized to Dag1^Control signal in each CA layer