Social Memory and Social Patterns Alterations in the Absence of STriatal-Enriched Protein Tyrosine Phosphatase.

Gloria Blázquez,Anna Castañé,Esther Pérez-Navarro,Mercè Masana,Jordi Alberch,Ana Saavedra

doi:10.3389/fnbeh.2018.00317

Abstract

STriatal-Enriched protein tyrosine Phosphatase (STEP) is a neural-specific protein that opposes the development of synaptic strengthening and whose levels are altered in several neurodegenerative and psychiatric disorders. Since STEP is expressed in brain regions implicated in social behavior, namely the striatum, the CA2 region of the hippocampus, cortex and amygdala, here we investigated whether social memory and social patterns were altered in STEP knockout (KO) mice. Our data robustly demonstrated that STEP KO mice presented specific social memory impairment as indicated by the three-chamber sociability test, the social discrimination test, the 11-trial habituation/dishabituation social recognition test, and the novel object recognition test (NORT). This affectation was not related to deficiencies in the detection of social olfactory cues, altered sociability or anxiety levels. However, STEP KO mice showed lower exploratory activity, reduced interaction time with an intruder, less dominant behavior and higher immobility time in the tail suspension test than controls, suggesting alterations in motivation. Moreover, the extracellular levels of dopamine (DA), but not serotonin (5-HT), were increased in the dorsal striatum of STEP KO mice. Overall, our results indicate that STEP deficiency disrupts social memory and other social behaviors as well as DA homeostasis in the dorsal striatum.

Highlights

STriatal-Enriched protein tyrosine Phosphatase (STEP) is a neural-specific phosphatase that opposes the development of synaptic strengthening through the regulation of multiple kinases and glutamate receptor subunits critical for synaptic plasticity
WT and STEP KO mice spent more time exploring the mouse cage than the dummy cage (intragenotype comparison, Student’s t-test, WT: t(1,16.64)= 5.79, p < 0.001; STEP KO: t(1,12.84) = 9.33, p < 0.001), indicating comparable levels of sociability and similar time spent for memory acquisition (Figure 1A), total exploration time of both cages was lower in STEP KO mice compared to WT group (WT: 92.99 ± 7.64 s and STEP KO: 70.71 ± 3.48 s, Student’s t-test, t(1,15.31) = 2.65, p < 0.05)
It has been reported that STEP KO mice show improved cognitive performance in the Morris water maze and in the radial arm maze (Venkitaramani et al, 2011) as well as increased fear conditioning in the conditioning suppression food-motivated instrumental performance test (Olausson et al, 2012)

Summary

Introduction

STriatal-Enriched protein tyrosine Phosphatase (STEP) is a neural-specific phosphatase that opposes the development of synaptic strengthening through the regulation of multiple kinases and glutamate receptor subunits critical for synaptic plasticity. In another work, neither WT nor STEP KO mice spent more time exploring the novel mouse compared to the familiar one in the three-chamber sociability test (Goebel-Goody et al, 2012b) pointing at some procedural artifact. Given these controversial results and STEP expression profile, in the present work we sought to examine the role of STEP in social memory and further social patterns by thoroughly characterizing the social phenotype of STEP KO mice

Methods

Results

Conclusion