Figure 7. Conditional KO of β-neurexins in the hippocampal CA1 region impairs contextual memory: Model for β-neurexin action.
(A) Design of behavioral experiments (after Xu et al., 2012).
(B) Representative coronal images illustrating expression of Cre-EGFP in the CA1 region of the hippocampus after stereotactic injection (top) and zoomed CA1 image (bottom).
(C & D) Analysis of ΔCre- or Cre-injected mice in open field (C) and fear-conditioning tests (D). Open field behavior (analyzed in three 5 min segments) was quantified as spatial confinement (C, left), low mobility bouts (C, center), and total distance traveled (C, right). Fear-conditioning training exposed mice to three 30 s tones ending with 2 s electrical footshocks separated by 1 min intervals (D; left graphs, cumulative distributions; right summary graphs, mean fear-conditioning memory as measured by freezing). Data are means ± SEM; numbers of mice examined are shown in the graphs. Statistical analysis was performed by Student’s t-test (* p<0.05).
(E) Model for β-neurexin action. In wild-type excitatory synapses (left), presynaptic β-neurexins regulate endocannabinoid signaling by controlling postsynaptic 2-AG synthesis, possibly via trans-synaptic interaction with postsynaptic neuroligin isoforms that exclusively bind to β- but not α-neurexins lacking an insert in SS#4. In excitatory β-neurexin KO synapses (right), 2-AG synthesis is disinhibited, CB1Rs are activated, and synaptic strength is decreased; moreover, in burst-firing subiculum neurons LTP is blocked which may be responsible for the impairment in contextual memory.