scholarly journals α7 Nicotinic Receptor Subunits Are Not Necessary for Hippocampal-Dependent Learning or Sensorimotor Gating: A Behavioral Characterization of Acra7-Deficient Mice

1998 ◽  
Vol 5 (4) ◽  
pp. 302-316 ◽  
Author(s):  
Richard Paylor ◽  
Michelle Nguyen ◽  
Jacqueline N. Crawley ◽  
James Patrick ◽  
Arthur Beaudet ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Prepulse Inhibition ◽  
Spatial Learning ◽  
Behavioral Responses ◽  
Sensorimotor Gating ◽  
Mutant Mice ◽  
Learning Performance ◽  
Wild Type ◽  
Α7 Nachr ◽  
Α7 Nachrs

The α7 nicotinic acetylcholine receptor (nAChR) subunit is abundantly expressed in the hippocampus and contributes to hippocampal cholinergic synaptic transmission suggesting that it may contribute to learning and memory. There is also evidence for an association between levels of α7 nAChR and in sensorimotor gating impairments. To examine the role of α7 nAChRs in learning and memory and sensorimotor gating, Acra7 homozygous mutant mice and their wild-type littermates were tested in a Pavlovian conditioned fear test, for spatial learning in the Morris water task, and in the prepulse inhibition paradigm. Exploratory activity, motor coordination, and startle habituation were also evaluated. Acra7 mutant mice displayed the same levels of contextual and auditory-cue condition fear as wild-type mice. Similarly, there were no differences in spatial learning performance between mutant and wild-type mice. Finally,Acra7 mutant and wild-type mice displayed similar levels of prepulse inhibition. Other behavioral responses in Acra7 mutant mice were also normal, except for an anxiety-related behavior in the open-field test. The results of this study show that the absence of α7 nAChRs has little impact on normal, base-line behavioral responses. Future studies will examine the contribution of α7 nAChR to the enhancement of learning and sensorimotor gating following nicotine treatments.

scholarly journals BDNF haploinsufficiency induces behavioral endophenotypes of schizophrenia in male mice that are rescued by enriched environment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mahmoud Harb ◽  
Justina Jagusch ◽  
Archana Durairaja ◽  
Thomas Endres ◽  
Volkmar Leßmann ◽  
...  
Keyword(s):  
Prepulse Inhibition ◽  
Sensorimotor Gating ◽  
Enriched Environment ◽  
Fear Learning ◽  
Set Shifting ◽  
Wild Type ◽  
Mature Adult ◽  
Attentional Set ◽  
Attentional Set Shifting ◽  
The Brain

AbstractBrain-derived neurotrophic factor (BDNF) is implicated in a number of processes that are crucial for healthy functioning of the brain. Schizophrenia is associated with low BDNF levels in the brain and blood, however, not much is known about BDNF’s role in the different symptoms of schizophrenia. Here, we used BDNF-haploinsufficient (BDNF+/−) mice to investigate the role of BDNF in different mouse behavioral endophenotypes of schizophrenia. Furthermore, we assessed if an enriched environment can prevent the observed changes. In this study, male mature adult wild-type and BDNF+/− mice were tested in mouse paradigms for cognitive flexibility (attentional set shifting), sensorimotor gating (prepulse inhibition), and associative emotional learning (safety and fear conditioning). Before these tests, half of the mice had a 2-month exposure to an enriched environment, including running wheels. After the tests, BDNF brain levels were quantified. BDNF+/− mice had general deficits in the attentional set-shifting task, increased startle magnitudes, and prepulse inhibition deficits. Contextual fear learning was not affected but safety learning was absent. Enriched environment housing completely prevented the observed behavioral deficits in BDNF+/− mice. Notably, the behavioral performance of the mice was negatively correlated with BDNF protein levels. These novel findings strongly suggest that decreased BDNF levels are associated with several behavioral endophenotypes of schizophrenia. Furthermore, an enriched environment increases BDNF protein to wild-type levels and is thereby able to rescue these behavioral endophenotypes.

scholarly journals Enhanced Hippocampal CA1 LTP but Normal Spatial Learning in Inositol 1,4,5-trisphosphate 3-kinase(A)-Deficient Mice

1998 ◽  
Vol 5 (4) ◽  
pp. 317-330 ◽  
Author(s):  
Kisun Jun ◽  
Gildon Choi ◽  
Sung-Gu Yang ◽  
Kwan Yong Choi ◽  
Hyun Kim ◽  
...  
Keyword(s):  
Spatial Learning ◽  
Mutant Mice ◽  
Wild Type ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1 ◽  
Morris Water Maze Task ◽  
Significant Difference ◽  
Kinase A

To define the physiological role of IP33-kinase(A) in vivo, we have generated a mouse strain with a null mutation of the IP33-kinase(A) locus by gene targeting. Homozygous mutant mice were fully viable, fertile, apparently normal, and did not show any morphological anomaly in brain sections. In the mutant brain, the IP4 level was significantly decreased whereas the IP3 level did not change, demonstrating a major role of IP33-kinase(A) in the generation of IP4. Nevertheless, no significant difference was detected in the hippocampal neuronal cells of the wild-type and the mutant mice in the kinetics of Ca2+ regulation after glutamate stimulation. Electrophysiological analyses carried out in hippocampal slices showed that the mutation significantly enhanced the LTP in the hippocampal CA1 region, but had no effect on the LTP in dentate gyrus (DG). No difference was noted, however, between the mutant and the wild-type mice in the Morris water maze task. Our results indicate that IP33-kinase(A) may play an important role in the regulation of LTP in hippocampal CA1 region through the generation of IP4, but the enhanced LTP in the hippocampal CA1 does not affect spatial learning and memory.

scholarly journals Neuronal Menin Overexpression Rescues Learning and Memory Phenotype in CA1-Specific α7 nAChRs KD Mice

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3286
Author(s):  
Shadab Batool ◽  
Basma Akhter ◽  
Jawwad Zaidi ◽  
Frank Visser ◽  
Gavin Petrie ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Hippocampal Neurons ◽  
Suppressor Gene ◽  
Men1 Gene ◽  
Α7 Nachr ◽  
Subunit Expression ◽  
Dependent Learning ◽  
Α7 Nachrs

The perturbation of nicotinic cholinergic receptors is thought to underlie many neurodegenerative and neuropsychiatric disorders, such as Alzheimer’s and schizophrenia. We previously identified that the tumor suppressor gene, MEN1, regulates both the expression and synaptic targeting of α7 nAChRs in the mouse hippocampal neurons in vitro. Here we sought to determine whether the α7 nAChRs gene expression reciprocally regulates the expression of menin, the protein encoded by the MEN1 gene, and if this interplay impacts learning and memory. We demonstrate here that α7 nAChRs knockdown (KD) both in in vitro and in vivo, initially upregulated and then subsequently downregulated menin expression. Exogenous expression of menin using an AAV transduction approach rescued α7 nAChRs KD mediated functional and behavioral deficits specifically in hippocampal (CA1) neurons. These effects involved the modulation of the α7 nAChR subunit expression and functional clustering at the synaptic sites. Our data thus demonstrates a novel and important interplay between the MEN1 gene and the α7 nAChRs in regulating hippocampal-dependent learning and memory.

scholarly journals Title-Effects of Catha Edulis Forsk on Spatial Cognition and correlation with serum electrolytes in Wild- type Male White Albino Rats

2021 ◽  
Author(s):  
Abebaye Aragaw Limenie ◽  
Tesfaye Tolessa Dugul ◽  
Eyasu Mekonnen Eshetu
Keyword(s):  
Learning And Memory ◽  
Serum Calcium ◽  
Spatial Learning ◽  
Escape Latency ◽  
Albino Rats ◽  
Wild Type ◽  
Serum Electrolytes ◽  
Catha Edulis ◽  
Significant Difference ◽  
Wild Type Male

Background : The burdens of psychostimulant use disorders are becoming a worldwide problem. One of the psychostimulants widely consumed in Ethiopia and East African countries is Catha edulis Forsk (khat). However, no studies have been conducted on the cognitive effects of khat and its correlation with serum electrolytes. The present study was aimed to evaluate the effects of khat on cognitive functions and its correlation with serum electrolytes. Materials and Methods — A total of 36 adult (7-8 weeks) wild-type male Swiss albino rats weighing between 213 and 229g were used in this study. The rats were received crude khat extract subchronically (kesc) (100 mg/kg, 200 mg/kg and 300 mg/kg b.w), khat juice (khJ 2.5 mL/kg) and 2% tween 80 in distilled water (T80W- v/v, vehicle) and khat extract subacutely (kesa) (300 mg/kg). Spatial learning and memory were measured using Morris water maze model and serum electrolytes were measured using Cobas 6000. The data were analyzed using SPSS version 21.0 and Microsoft Excel. Results : Spatial learning was improved with trials across the groups, while average escape latency (s) and swim path-length (cm) of rats that received kesc 200 mg/kg (p<0.001 and p<0.001) and kesc 300 mg/kg (p<0.01 and p<0.001) was significantly greater than rats that received the vehicle. However, there was no significant difference in the latency between rats that received kesa 300mg/kg and vehicle (p>0.05). Thigmotaxis was significantly higher in rats that received all doses of khat extract (p<0.001). The time spent in the target quadrant in rats that received kesc 300 mg/kg was significantly reduced (p<0.05). Serum calcium level was inversely correlated with the escape latency (R=-0.417, p<0.05) in rats that received khat. Conclusions : khat extract and juice administered subchronically, but not subacute administration, impaired learning and memory in rats and was associated with serum calcium reduction. The neuronal basis for such alteration should be investigated.

scholarly journals Longitudinal Microglial Activation in Tau Transgenic P301S Mice Predicts Increased Tau Accumulation and Deteriorated Spatial Learning

2020 ◽  
Author(s):  
Florian Eckenweber ◽  
Jose Medina Luque ◽  
Tanja Blume ◽  
Christian Sacher ◽  
Gloria Biechele ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Transgenic Mice ◽  
Mouse Models ◽  
Spatial Learning ◽  
Microglial Activation ◽  
Amyloid Β ◽  
Learning Performance ◽  
Wild Type ◽  
Tspo Expression

Abstract Background: P301S tau transgenic mice show age-dependent accumulation of neurofibrillary tangles in brainstem, hippocampus, and neocortex, leading to neuronal loss and cognitive deterioration. However, there is hitherto only sparse documentation of the role of neuroinflammation in tau mouse models. Thus, we analyzed longitudinal microglial activation by small animal 18kDa translocator protein positron-emission-tomography (TSPO µPET) imaging in vivo , in conjunction with terminal assessment of tau pathology, spatial learning, and cerebral glucose metabolism. Methods: Transgenic P301S (n=33) and wild-type (n=18) female mice were imaged by 18 F-GE-180 TSPO µPET at the ages of 1.9, 3.9 and 6.4 months. We conducted behavioral testing in the Morris water maze, 18 F-fluordesoxyglucose ( 18 F-FDG) µPET and AT8 tau immunohistochemistry at 6.3-6.7 months. Terminal microglial immunohistochemistry served for validation of TSPO µPET results in vivo, applying target regions in brainstem, cortex, cerebellum and hippocampus. We compared the results with our historical data in amyloid -β mouse models. Results: TSPO expression in all target regions of P301S mice increased exponentially from 1.9 to 6.4 months, leading to significant differences in the contrasts with wild-type mice at 6.4 months (+11-23%, all p<0.001), but the apparent microgliosis proceeded more slowly than in our experience in amyloid-β mouse models. Spatial learning and glucose metabolism of AT8-positive P301S mice were significantly impaired at 6.3/6.5 months compared to the wild-type group. Longitudinal increases in TSPO expression predicted greater tau accumulation and lesser spatial learning performance at 6.7/6.3 months. Conclusions: Monitoring of microglial activation in P301S tau transgenic mice by TSPO µPET indicates a delayed time course when compared to amyloid-β mouse models. Detrimental associations of microglial activation with outcome parameters are opposite to earlier data in amyloid-β mouse models. The contribution of microglial response to pathology accompanying amyloid-β and tau over-expression merits further investigation.

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