China
Africa
Explore chapters and articles related to this topic
Animal Models of Down Syndrome and Other Genetic Diseases Associated with Mental Retardation
Published in Merlin G. Butler, F. John Meaney, Genetics of Developmental Disabilities, 2019
Angela J. Villar, Charles J. Epstein
Mutations in the X-linked FMR2 gene cause FRAXE, a nonspecific form of X-linked MR with an incidence of 1:50,000 (185). Methylation of an expanded CCG trinucleotide repeat located in exon 1 of the gene results in transcriptional silencing and lack of its product, the FMR2 protein. This protein has been hypothesized to be a transcriptional activator (186). Fmr2 knockout mice (187) display a delaydependent deficit in contextual fear conditioning, indicating dysfunction of the hippocampus and amygdala (188,189), a slight deficit in spatial learning in a Morris water maze task, and increased sensitivity to the heat source in the hot plate test. Surprisingly, LTP was found to be enhanced in hippocampal slices of Fmr2 knockouts as compared to control littermate. Although a number of studies have suggested that diminished LTP is associated with memory impairment (60,61), these data suggest that increased LTP also may be as detrimental to the cognitive processes as diminished LTP (187).
Biomarkers for Organophosphate Poisoning: Physiological and Pathological Responses
Published in Brian J. Lukey, James A. Romano, Salem Harry, Chemical Warfare Agents, 2019
Arik Eisenkraft, Avshalom Falk, Kevin G. McGarry Jr.
Animals surviving a high-level (~1 × LD50 or more) exposure to CWNA/OP display long-term cognitive and emotional deficiencies, of which the most studied are spatial memory deficiency, manifested by poor learning in the Morris Water Maze (MWM), and anxiety-like behavior, which is demonstrated by decreased activity in the open-field activity test (Grauer et al., 2008; Raveh et al., 2003;). These deficiencies are generally associated with neuronal loss in the hippocampus and amygdala, respectively (Aroniadou-Andrejaska et al., 2016; Collombet, 2011). Using other behavioral paradigms such as contextual fear conditioning and comparisons of seizing and non-seizing similarly exposed animals have shown that long-term cognitive impairment was associated with the occurrence of acute seizures, as the performance of exposed non-seizing animals was similar to that of unexposed controls (Langston et al., 2012; Moffett et al., 2011). Animals exposed to single or repeated sublethal and non-seizurogenic doses of NAs experienced long-term anxiety-like and other behavioral deficits, although acute toxicity was mild or not seen (Bloch-Shilderman et al., 2008; Kassa et al., 2001; Mamczarz et al., 2010; Smith et al., 2016a). The mechanism of these effects is less well understood and may involve pathophysiological pathways other than the pathway of high-level poisoning outlined earlier (Allon et al., 2011; Mamczarz et al., 2010).
Histamine as Neurotransmitter
Published in Divya Vohora, The Third Histamine Receptor, 2008
Oliver Selbach, Helmut L. Haas
HDC-KO mice lack the ability to remain awake in a novel environment, concurrent with impairments in hippocampal theta and sustained cortical arousal [60]. They also show deficient episodic object memory (discrimination based on temporal relationships) but an increased negatively reinforced water-maze performance [365]. Likewise, HDC-KO mice show improved learning and memory retention of contextual fear conditioning along with enhanced hippocampal CA1 LTP before and decreased LTP after training [363]. Injection of histamine (icv) immediately after training normalized conditioned contextual fear responses in HDC-KO mice, whereas microinjection of histamine into the ventral hippocampus, amygdala, or nucleus acccumbens of rats impaired novel object-motivated exploratory behavior through H1R [369] or H2R activation [293,370–372]. In contrast, acute histamine infusion into the CA1 region of rats immediately after training, but not later, enhances consolidation of inhibitory avoidance memory through an H2R-dependent mechanism without altering locomotor activity, exploratory behavior, anxiety state, or retrieval of the avoidance response [360]. Notably, the effect of a loss of HDC function on object recognition, water-maze, and rotorod performance seem to be sex-dependent, emphasizing the importance of gender in the interpretation of the role of histaminergic neurotransmission in brain function [373].
Systems consolidation and fear memory generalisation as a potential target for trauma-related disorders
Published in The World Journal of Biological Psychiatry, 2022
Lizeth K. Pedraza, Rodrigo O. Sierra, Lucas de Oliveira Alvares
The assumption about the influences of individual factors is not different in animal research. Shumake et al. (2018) developed a data-driven approach in order to define a standard criterion for remission after extinction and identify individual differences in the rate of fear attenuation. The remission was achieved when the animals behaved as if they had never been conditioned (low fear responses). The criterion was based on a logistic regression analysis applied to freezing data from a large sample of rats that either underwent fear conditioning or did not. As evidenced in humans, animals can be clustered according to phenotypic extinction, highlighting the individual responses in rodents to the same training and extinction protocol. This result matches with our recent findings demonstrating that naïve animals are differentially susceptible to discrimination or generalisation after contextual fear conditioning. This heterogeneity affects the subsequent fear extinction outcome (Pedraza et al. 2019). Similar correlative individualities were found by Monfils et al. (2019) showing that CO2 reactivity is able to predict extinction phenotype in rats.
Depletion of dietary phytoestrogens reduces hippocampal plasticity and contextual fear memory stability in adult male mouse
Published in Nutritional Neuroscience, 2021
Gürsel Çalışkan, Syed Ahsan Raza, Yunus E. Demiray, Emre Kul, Kiran V. Sandhu, Oliver Stork
Fear conditioning was conducted in a soundproofed cubicle chamber (16 × 16 × 20 cm) made of acrylic glass. The conditioning arena is equipped with a grid floor for the delivery of foot shocks, a ventilation fan and a loudspeaker (background noise 70 dB SLP, light intensity 10 Lux; TSE Systems, Bad Homburg, Germany). Mice were individually habituated to the conditioning chamber for two days twice per day for 6 min, before conditioning. Contextual fear conditioning training session was performed on the third day. Mice were placed in the conditioning chamber and after two minutes of initial context exposure, 3 unsignalled foot shocks (0.4 mA for 1 s) with an inter-stimulus interval of 20 s were delivered [22]. Mice were placed back in their home cages 2 min after the last stimulus. Conditioned contextual memory was tested either one day (Recent memory) or 14 days (Remote memory) after training session by placing the mice in the original training context for a period of 6 min. The immobility periods >1 s that corresponds to animals’ freezing behavior were detected online via a photobeam detection system. Fear memory is recorded as the percentage of time spent freezing during the sessions.
Behavioral effects of chronic stress in Carioca high- and low-conditioned freezing rats
Published in Stress, 2021
Yury V. Lages, Silvia S. Maisonnette, Beatriz Marinho, Flávia P. Rosseti, Thomas E. Krahe, J. Landeira-Fernandez
A total of 105 male Wistar rats, 110 days old, were obtained from the Laboratory of Behavioral Neuroscience (LANEC) of the Pontifical Catholic University of Rio de Janeiro. We chose to use only male rats because CHF males display a stronger response to context fear conditioning than females (Gomes et al., 2011). Two outbred strains were used, CHF (n = 52) and CLF (n = 53), that were selectively bred for high- and low-conditioned freezing responses to contextual cues as previously described (Gomes & Landeira-Fernandez, 2008). Bidirectional selective breeding is based on the animals’ freezing response to contextual cues. After the third generation (Gomes et al., 2011), strains possessing markedly opposed freezing responses could be identified (i.e. CHF and CLF lines). The protocol used for contextual fear conditioning is described in detail below. Except as specified below, animals were kept on a 12 h/12 h light/dark cycle (lights on at 7:00 AM, lights off at 7:00 PM) at a controlled temperature (24 °C ± 1 °C) with free access to food and water. The behavioral experiments were conducted between 9:00 AM and 1:00 PM and performed in accordance with the Declaration of Helsinki and Guide for the Care and Use of Laboratory Animals as adopted and promulgated by the National Institutes of Health.