scholarly journals Decrease of SYNGAP1 in GABAergic cells impairs inhibitory synapse connectivity, synaptic inhibition and cognitive function

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Martin H. Berryer ◽  
Bidisha Chattopadhyaya ◽  
Paul Xing ◽  
Ilse Riebe ◽  
Ciprian Bosoi ◽  
...  
2009 ◽  
Vol 101 (3) ◽  
pp. 1179-1191 ◽  
Author(s):  
Ewa D. Zarnowska ◽  
Ruth Keist ◽  
Uwe Rudolph ◽  
Robert A. Pearce

γ-Aminobutyric acid type A (GABAA) receptor α5 subunits, which are heavily expressed in the hippocampus, are potential drug targets for improving cognitive function. They are found at synaptic and extrasynaptic sites and have been shown to mediate tonic inhibition in pyramidal neurons. We tested the hypothesis that α5 subunits also contribute to synaptic inhibition by measuring the effect of diazepam (DZ) on spontaneous and stimulus-evoked inhibitory postsynaptic currents (IPSCs) in genetically modified mice carrying a point mutation in the α5 subunit (α5-H105R) that renders those receptors insensitive to benzodiazepines. In wild type mice, DZ (1 μM) increased the amplitude of spontaneous IPSCs (sIPSCs) and stimulus-evoked GABAA,slow IPSCs (eIPSCs) and prolonged the decay of GABAA,fast sIPSCs. In α5-mutant mice, DZ increased the amplitude of a small-amplitude subset of sIPSCs (<50 pA) and eIPSCs (<300 pA) GABAA,slow and prolonged the decay of GABAA,fast sIPSCs, but failed to increase the amplitude of larger sIPSCs and eIPSCs GABAA,slow. These results indicate that α5 subunits contribute to a large-amplitude subset of GABAA,slow synapses and implicate these synapses in modulation of cognitive function by drugs that target α5 subunits.


GeroPsych ◽  
2011 ◽  
Vol 24 (2) ◽  
pp. 83-92 ◽  
Author(s):  
Valentina A. Tesky ◽  
Christian Thiel ◽  
Winfried Banzer ◽  
Johannes Pantel

To investigate the effects of leisure activities on cognitive performance of healthy older subjects, an innovative intervention program was developed. Frequent participation in cognitively stimulating activities (i.e., reading, playing chess, or playing music) is associated with reduced risk of dementia. AKTIVA (active cognitive stimulation – prevention in the elderly) is an intervention program designed to enhance cognitive stimulation in everyday life by increasing cognitive stimulating leisure activities. The present study determines the effects of AKTIVA on cognitive function, mood and attitude toward aging in a sample of older participants from the general population. Several measurement instruments were used including the Alzheimer’s Disease Assessment Scale (ADAS-Cog), the Trail-Making Test (TMT), and the Memory Complaint Questionnaire (MAC-Q). Initially, the sample consisted of 307 older persons (170 female, 72 ± 7 years). The intervention was evaluated with a randomized, controlled pre-post follow-up design. Participants were randomly assigned to one of three conditions: AKTIVA intervention (n = 126), AKTIVA intervention plus nutrition and exercise counseling (n = 84), no-intervention control group (n = 97). The AKTIVA intervention consisted of 8 weekly sessions and two booster sessions after a break of 4 months. Participation in the group program resulted in positive effects on cognitive function and attitude toward aging for subassembly groups. Older persons (≥ 75 years) showed enhanced speed of information processing (by TMT Version A) (F = 4.17*, p < .05); younger participants (< 75 years) showed an improvement in subjective memory decline (by MAC-Q) (F = 2.55*, p < .05). Additionally, AKTIVA enhanced the frequency of activities for leisure activities for subassembly groups. The results of this study suggest that the AKTIVA program can be used to increase cognitively stimulating leisure activities in the elderly. Further research is necessary to identify the long-term effects of this intervention particularly with respect to the prevention of dementia.


2008 ◽  
Author(s):  
John Gunstad ◽  
Mary B. Spitznagel ◽  
Kelly Stanek ◽  
Faith Luyster ◽  
James Rosneck ◽  
...  

2013 ◽  
Author(s):  
Sheryl L. Reminger ◽  
Stefanie Ames ◽  
Laura Q. Rogers ◽  
Dian Canaday ◽  
Rita Trammell ◽  
...  

2010 ◽  
Author(s):  
Steven L. Schandler ◽  
John V. Flowers ◽  
Gily Meir ◽  
Rachel Ho ◽  
Gina L. Cristiano ◽  
...  

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