Mice null for NEDD9 (HEF1α) display extensive hippocampal dendritic spine loss and cognitive impairment.

NEDD9 (neural precursor cell expressed, developmentally down-regulated 9) is a member of the CAS (Crk-associated substrate) family of scaffolding proteins that regulate cell adhesion and migration. A Nedd9 knock-out/lacZ knock-in mouse (Nedd9(-/)(-)) was developed in order to study Nedd9 expression and function in the nervous system. Herein we show that NEDD9 is expressed in the adult brain and is prominently expressed in the hippocampus. Behavioral testing uncovered functional deficits in Nedd9(-)(/)(-) mice. In the Morris water maze test, Nedd9(-)(/)(-) mice showed deficits in both the ability to learn the task as well as in their ability to recall the platform location. There was no change in the gross morphology of the hippocampus, and stereological analysis of BrdU-labeled newly formed hippocampal cells suggested that this defect is not secondary to altered neurogenesis. However, analysis of the hippocampus revealed extensive loss of dendritic spine density in both the dentate gyrus (DG) and CA1 regions. Spine loss occurred equally across all branch orders and regions of the dendrite. Analysis of spine density in Nedd9(-)(/)(-) mice at 1.5, 6 and 10 months revealed an age-dependent spine loss. This work shows that NEDD9 is required for the maintenance of dendritic spines in the hippocampus, and suggests it could play a role in learning and memory.

Interval schedule performance in the goldfish Carassius auratus.

In experiment 1, five goldfish (Carassius auratus) paddle-pressed on fixed-interval (FI) and variable-interval (VI) schedules for food pellet reinforcement. The order of conditions was FI 60 s, FI 240 s, FI 30 s, FI 60 s, and VI 60 s. FI responding showed a scalloped pattern and response-rate break points were proportional to interval duration. Post-food wait times varied with interval duration, but were not proportional. Response rate on VI was constant. Experiment 2 studied the properties of food reinforcement as a time marker. The same five fish were presented an FI 60 s schedule of reinforcement with 25% of intervals ending in non-reinforcement (N). The fish responded faster and paused less following the omission stimulus (omission effect) and response rate was flat or declined through post-N intervals.