Mice lacking synapsin III show abnormalities in explicit memory and conditioned fear

Abstract

Synapsin III is a neuron-specific phosphoprotein that plays an important role in synaptic transmission and neural development. While synapsin III is abundant in embryonic brain, expression of the protein in adults is reduced and limited primarily to the hippocampus, olfactory bulb and cerebral cortex. Given the specificity of synapsin III to these brain areas and because it plays a role in neurogenesis in the dentate gyrus, we investigated whether it may affect learning and memory processes in mice. To address this point, synapsin III knockout mice were examined in a general behavioral screen, several tests to assess learning and memory function, and conditioned fear. Mutant animals displayed no anomalies in sensory and motor function or in anxiety- and depressive-like behaviors. Although mutants showed minor alterations in the Morris water maze, they were deficient in object recognition 24 h and 10 days after training and in social transmission of food preference at 20 min and 24 h. In addition, mutants displayed abnormal responses in contextual and cued fear conditioning when tested 1 or 24 h after conditioning. The synapsin III knockout mice also showed aberrant responses in fear-potentiated startle. As synapsin III protein is decreased in schizophrenic brain and because the mutant mice do not harbor obvious anatomical deficits or neurological disorders, these mutants may represent a unique neurodevelopmental model for dissecting the molecular pathways that are related to certain aspects of schizophrenia and related disorders.

Keywords: Synapsin III; behavior; conditioned fear; explicit memory; knockout mice.

Figure 1. Responses in the Morris water maze by WT and Syn3-KO mice

(a) Swim distance in the visible platform test. (b) Swim distances over the 6 days of acquisition and 2 days of reversal testing. (c) Swim velocities during acquisition and reversal testing. (d) Swim distances during the first day of acquisition testing over the 4 test trials. (e) Tracings of swim patterns for representative WT and Syn3-KO mice during acquisition and reversal trials. The apex of the water maze in each tracing is north and the platform location is designated by a filled square. (f) Swim distances during probe trials during acquisition testing on days 3 and 6, and following reversal on day 8. (g) Tracings of swim patterns for representative WT and Syn3-KO mice during probe trials on days 3 and 6 during acquisition and on day 8 for reversal. n = 11-12 mice/genotype; *P<0.05 from the WT controls; +P<0.05 compared to test day 1 for all mice; #P<0.05 compared to NE quadrant; ^xP<0.05 compared to SW quadrant.

Figure 2. Object recognition and social transmission of food preference responses of WT and Syn3-KO mice

(a) Object recognition performance at 20 min, 24 hr, and at 10 days for WT and Syn3-KO animals. (b) Responses by WT and Syn3-KO mice in the social transmission of food preference test. (c) Contacts with objects during training, and for the 20 min, 24 hrs, and 10 day tests. (d) Total diet consumed by the demonstrator and the percent time tester mice spent with the demonstrator after the latter was returned to home cage after diet consumption. (e) Total bowl contacts made by WT and Syn3-KO mice at the 20 min and 24 hr test. n = 10 mice/genotype; *P<0.05 from the WT controls; +P<0.05 compared to the preference at 20 min; ˆP<0.05 compared to the demonstrator diet.

Figure 3. Conditioned fear responses of WT and Syn3-KO mice

(a-b) Percent freezing responses in contextual fear conditioning at 1 (a) and 24 hr (b). (c-d) Percent freezing responses prior to and during presentation of the CS in cued fear conditioning at 1 (c) and 24 hr (d). (e) Baseline startle amplitudes on day 1 of fear-potentiated startle. (f) Fear-potentiated startle following CS-UCS conditioning. n = 10 mice/genotype; *P<0.05 from the WT controls; #P<0.05 compared to 1 hr context test; +P<0.05 compared to pre-CS freezing.