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Section MOLECULAR NEUROSCIENCE Materials and Methods
The heterozygous knockout mutant of the Satbl gene has been generated using the Cre-loxP system. Thirty two male (8 WT/8 SATB1 (+/-)) and female (8 WT/8 SATB1 (+/-)) mice at an age of two months were used. A battery of sensorimotor tasks was performed to assess coordination, climbing, locomotion and orienting reactions). In each test, the time was measured with the criterion of 120 s to complete. The mice were subjected to: walking initiation, bridges (1, 2 and 4 cm), wire suspension, turning in an alley, turning on an inclined screen. Spontaneous horizontal and vertical (rearing) locomotor activities and average speed were measured during 5 min using a Infrared Actimeter (Actitrack, Panlab, Barcelona, Spain). For assessment short-term memory in passive avoidance tests the Shuttle Boxes LE918 (Panlab, Barcelona, Spain) were used. During the acquisition/conditioning phase the animal is placed in the white compartment. When the animal innately crosses to the black compartment it receives a mild foot shock. During the test phase the animal is again placed in the white compartment and the latency of the entrance to the black compartment is evaluated. Startle response and prepulse inhibition of acoustic startle responses were measured by the Start and Fear Combined system (Panlab, Barcelona, Spain). Statistical analysis was performed using Satistica 10.0 software.
Results
Sensorimotor tests showed no impairment in locomotor activity of Satbl (+/-) male and female mice. The four tested groups completed all the sensorimotor tasks. However in the locomotor activity test Satbl (+/-) mice demonstrated an increased locomotion compared with WT mice. Distance moved in the central zone by male and female Satbl (+/-) mice was significantly higher compared with WT mice. Significant increase in number of rearing in Satb1(+/-) female mice were showed. There were no significant differences due to genotype in the startle response and prepulse inhibition test. There was no difference in latency of the entrance to the black compartment between conditioning and test phase in passive avoidance task in Satbl (+/-) male and female mice which indicates about deficit in retention of memory for an aversive experience in Satbl (+/-) compared with WT mice.
Conclusions
Taken together, our findings suggest that Satbl (+/-) presented behavioral alterations compared to their wildtype littermates, such as: hyperlocomotion and deficit in learning capacity.
Acknowledgements
Research carried out with the financial support of the grant of the Russian Scientific Foundation (project №l5-l4-l002l)
Postnatal Dlx1&2 Functions in Cortical Interneuron Development
John Rubenstein*
UCSF Weill Institute for Neurosciences, University of California at San Francisco, San Francisco, CA 94143, USA. * Presenting e-mail: [email protected]
The postnatal functions of the Dlxl&2 transcription factors in cortical interneurons (CINs) are unknown. Here, using conditional Dlxl, Dlx2 and Dlxl&2 knockouts (CKOs), we defined their roles in specific CINs. The CKOs had dendritic, synaptic and survival defects, affecting even PV+ CINs. We provide evidence that DLX2 directly drives GADl, GAD2 and VGat expression, and show that mutants had reduced mIPSC amplitude. Furthermore, the mutants formed fewer GABAergic synapses on excitatory neurons and had reduced mIPSC frequency. Furthermore, Dlxl/2 CKO had hy-poplastic dendrites, fewer excitatory synapses, and reduced excitatory input. We provide evidence that some of these phenotypes were due to reduced expression of GRIN2B (a subunit of the NMDA receptor), a high confidence Autism gene. Thus, Dlxl&2 direct coordinate key components of CIN postnatal development by promoting their excitability, inhibitory functions and survival.
OM&P
Opera Med Physiol 2016 Vol. 2 (S1) 25
