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PLoS Biology Jun 2024Despite the diverse genetic origins of autism spectrum disorders (ASDs), affected individuals share strikingly similar and correlated behavioural traits that include...
Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice.
Despite the diverse genetic origins of autism spectrum disorders (ASDs), affected individuals share strikingly similar and correlated behavioural traits that include perceptual and sensory processing challenges. Notably, the severity of these sensory symptoms is often predictive of the expression of other autistic traits. However, the origin of these perceptual deficits remains largely elusive. Here, we show a recurrent impairment in visual threat perception that is similarly impaired in 3 independent mouse models of ASD with different molecular aetiologies. Interestingly, this deficit is associated with reduced avoidance of threatening environments-a nonperceptual trait. Focusing on a common cause of ASDs, the Setd5 gene mutation, we define the molecular mechanism. We show that the perceptual impairment is caused by a potassium channel (Kv1)-mediated hypoexcitability in a subcortical node essential for the initiation of escape responses, the dorsal periaqueductal grey (dPAG). Targeted pharmacological Kv1 blockade rescued both perceptual and place avoidance deficits, causally linking seemingly unrelated trait deficits to the dPAG. Furthermore, we show that different molecular mechanisms converge on similar behavioural phenotypes by demonstrating that the autism models Cul3 and Ptchd1, despite having similar behavioural phenotypes, differ in their functional and molecular alteration. Our findings reveal a link between rapid perception controlled by subcortical pathways and appropriate learned interactions with the environment and define a nondevelopmental source of such deficits in ASD.
Topics: Animals; Disease Models, Animal; Mice; Visual Perception; Haploinsufficiency; Avoidance Learning; Autism Spectrum Disorder; Male; Behavior, Animal; Mice, Inbred C57BL; Histone-Lysine N-Methyltransferase; Autistic Disorder
PubMed: 38857283
DOI: 10.1371/journal.pbio.3002668 -
Psychiatria Polska Feb 2024The study aimed to validate the Brief Experiential Avoidance Questionnaire (BEAQ) in Polish and establish its psychometric properties.
OBJECTIVES
The study aimed to validate the Brief Experiential Avoidance Questionnaire (BEAQ) in Polish and establish its psychometric properties.
METHODS
A representative sample of the Polish population (N = 1,216) in terms of gender, age, education, and place of residence participated in the online study. The adaptation was conducted with back translation to preserve fidelity to the original version. Apart from BEAQ, participants filled in questionnaires measuring the levels of depression, cognitive fusion, mindfulness and psychological flexibility.
RESULTS
Confirmatory factor analysis showed that the unidimensional model insufficiently fit the data, similarly to other reports on BEAQ validations. Exploratory factor analysis using oblimin rotation extracted two factors labeled "cognitive-emotional avoidance" and "behavioral avoidance" with internal consistency (α) of 0.78 and 0.74, respectively, and stability over time of r = 0.79 and 0.75 in a 21-day test-retest measurement. The subscales demonstrated satisfactory convergent and discriminant validity.
CONCLUSIONS
The Polish BEAQ validation demonstrates it is a tool that can be successfully used in research and clinical practice as it provides a reliable measure of experiential avoidance and is convenient thanks to its limited duration.
Topics: Humans; Female; Male; Poland; Adult; Psychometrics; Surveys and Questionnaires; Reproducibility of Results; Avoidance Learning; Middle Aged; Young Adult
PubMed: 38852185
DOI: 10.12740/PP/162165 -
Journal of Neuroscience Research Jun 2024Childhood obesity increases the risk of health and cognitive disorders in adulthood. Consuming high-fat diets (HFD) during critical neurodevelopmental periods, like...
Early-life and chronic exposure to high-fat diet alters noradrenergic and glutamatergic neurotransmission in the male rat amygdala and hippocampus under cognitive challenges.
Childhood obesity increases the risk of health and cognitive disorders in adulthood. Consuming high-fat diets (HFD) during critical neurodevelopmental periods, like childhood, impairs cognition and memory in humans and animals, affecting the function and connectivity of brain structures related to emotional memory. However, the underlying mechanisms of such phenomena need to be better understood. This study aimed to investigate the neurochemical profile of the amygdala and hippocampus, brain structures involved in emotional memory, during the acquisition of conditioned odor aversion in male rats that consumed a HFD from weaning to adulthood. The rats gained weight, experienced metabolic changes, and reduced insulin sensitivity and glucose tolerance. Rats showed enhanced odor aversion memory, contrary to the expected cognitive impairments. This memory enhancement was accompanied by increased noradrenergic and glutamatergic neurotransmission in the amygdala and hippocampus. Importantly, this upregulation was specific to stimuli exposure, as basal neurotransmitter levels remained unaltered by the HFD. Our results suggest that HFD modifies cognitive function by altering neurochemical signaling, in this case, upregulating neurotransmitter levels rendering a stronger memory trace, demonstrating that metabolic dysfunctions do not only trigger exclusively detrimental plasticity processes but also render enhanced plastic effects depending on the type of information.
Topics: Animals; Male; Diet, High-Fat; Hippocampus; Amygdala; Synaptic Transmission; Rats; Glutamic Acid; Norepinephrine; Rats, Wistar; Cognition; Avoidance Learning
PubMed: 38847288
DOI: 10.1002/jnr.25360 -
Current Neuropharmacology 2024The thalamus is a phylogenetically well-preserved structure. Known to densely contact cortical regions, its role in the transmission of sensory information to the...
BACKGROUND
The thalamus is a phylogenetically well-preserved structure. Known to densely contact cortical regions, its role in the transmission of sensory information to the striatal complex has been widely reconsidered in recent years.
METHODS
The parafascicular nucleus of the thalamus (Pf) has been implicated in the orientation of attention toward salient sensory stimuli. In a stimulus-driven reward-seeking task, we sought to characterize the electrophysiological activity of Pf neurons in rats.
RESULTS
We observed a predominance of excitatory over inhibitory responses for all events in the task. Neurons responded more strongly to the stimulus compared to lever-pressing and reward collecting, confirming the strong involvement of the Pf in sensory information processing. The use of long sessions allowed us to compare neuronal responses to stimuli between trials when animals were engaged in action and those when they were not. We distinguished two populations of neurons with opposite responses: MOTIV+ neurons responded more intensely to stimuli followed by a behavioral response than those that were not. Conversely, MOTIV- neurons responded more strongly when the animal did not respond to the stimulus. In addition, the latency of excitation of MOTIV- neurons was shorter than that of MOTIV+ neurons.
CONCLUSION
Through this encoding, the Pf could perform an early selection of environmental stimuli transmitted to the striatum according to motivational level.
Topics: Animals; Reward; Neurons; Male; Intralaminar Thalamic Nuclei; Rats; Rats, Wistar; Conditioning, Operant; Action Potentials
PubMed: 38847144
DOI: 10.2174/1570159X22666240131114225 -
ENeuro Jun 2024The retrosplenial cortex (RSC) is a hub of diverse afferent and efferent projections thought to be involved in associative learning. RSC shows early pathology in mild...
The Granular Retrosplenial Cortex Is Necessary in Male Rats for Object-Location Associative Learning and Memory, But Not Spatial Working Memory or Visual Discrimination and Reversal, in the Touchscreen Operant Chamber.
The retrosplenial cortex (RSC) is a hub of diverse afferent and efferent projections thought to be involved in associative learning. RSC shows early pathology in mild cognitive impairment and Alzheimer's disease (AD), which impairs associative learning. To understand and develop therapies for diseases such as AD, animal models are essential. Given the importance of human RSC in object-location associative learning and the success of object-location associative paradigms in human studies and in the clinic, it would be of considerable value to establish a translational model of object-location learning for the rodent. For this reason, we sought to test the role of RSC in object-location learning in male rats using the object-location paired-associates learning (PAL) touchscreen task. First, increased cFos immunoreactivity was observed in granular RSC following PAL training when compared with extended pretraining controls. Following this, RSC lesions following PAL acquisition were used to explore the necessity of the RSC in object-location associative learning and memory and two tasks involving only one modality: trial-unique nonmatching-to-location for spatial working memory and pairwise visual discrimination/reversal. RSC lesions impaired both memory for learned paired-associates and learning of new object-location associations but did not affect performance in either the spatial or visual single-modality tasks. These findings provide evidence that RSC is necessary for object-location learning and less so for learning and memory involving the individual modalities therein.
Topics: Animals; Male; Memory, Short-Term; Spatial Memory; Association Learning; Rats, Long-Evans; Visual Perception; Rats; Gyrus Cinguli; Reversal Learning; Conditioning, Operant; Discrimination, Psychological; Cerebral Cortex
PubMed: 38844347
DOI: 10.1523/ENEURO.0120-24.2024 -
Science (New York, N.Y.) Jun 2024In addition to their intrinsic rewarding properties, opioids can also evoke aversive reactions that protect against misuse. Cellular mechanisms that govern the interplay...
In addition to their intrinsic rewarding properties, opioids can also evoke aversive reactions that protect against misuse. Cellular mechanisms that govern the interplay between opioid reward and aversion are poorly understood. We used whole-brain activity mapping in mice to show that neurons in the dorsal peduncular nucleus (DPn) are highly responsive to the opioid oxycodone. Connectomic profiling revealed that DPn neurons innervate the parabrachial nucleus (PBn). Spatial and single-nuclei transcriptomics resolved a population of PBn-projecting pyramidal neurons in the DPn that express μ-opioid receptors (μORs). Disrupting μOR signaling in the DPn switched oxycodone from rewarding to aversive and exacerbated the severity of opioid withdrawal. These findings identify the DPn as a key substrate for the abuse liability of opioids.
Topics: Animals; Male; Mice; Analgesics, Opioid; Connectome; Mice, Inbred C57BL; Neurons; Opioid-Related Disorders; Oxycodone; Parabrachial Nucleus; Prefrontal Cortex; Pyramidal Cells; Receptors, Opioid, mu; Reward; Substance Withdrawal Syndrome; Transcriptome; Avoidance Learning
PubMed: 38843332
DOI: 10.1126/science.adn0886 -
PloS One 2024A large body of evidence has shown that treatments that interfere with memory consolidation become ineffective when animals are subjected to an intense learning...
A large body of evidence has shown that treatments that interfere with memory consolidation become ineffective when animals are subjected to an intense learning experience; this effect has been observed after systemic and local administration of amnestic drugs into several brain areas, including the striatum. However, the effects of amnestic treatments on the process of extinction after intense training have not been studied. Previous research demonstrated increased spinogenesis in the dorsomedial striatum, but not in the dorsolateral striatum after intense training, indicating that the dorsomedial striatum is involved in the protective effect of intense training. To investigate this issue, male Wistar rats, previously trained with low, moderate, or high levels of foot shock, were used to study the effect of tetrodotoxin inactivation of dorsomedial striatum on memory consolidation and subsequent extinction of inhibitory avoidance. Performance of the task was evaluated during seven extinction sessions. Tetrodotoxin produced a marked deficit of memory consolidation of inhibitory avoidance trained with low and moderate intensities of foot shock, but normal consolidation occurred when a relatively high foot shock was used. The protective effect of intense training was long-lasting, as evidenced by the high resistance to extinction exhibited throughout the extinction sessions. We discuss the possibility that increased dendritic spinogenesis in dorsomedial striatum may underly this protective effect, and how this mechanism may be related to the resilient memory typical of post-traumatic stress disorder (PTSD).
Topics: Animals; Male; Rats, Wistar; Extinction, Psychological; Rats; Avoidance Learning; Corpus Striatum; Tetrodotoxin; Memory Consolidation; Amnesia; Electroshock
PubMed: 38843228
DOI: 10.1371/journal.pone.0305066 -
Journal of the Experimental Analysis of... Jul 2024A challenge in carrying out matching analyses is to deal with undefined log ratios. If any reinforcer or response rate equals zero, the logarithm of the ratio is...
A challenge in carrying out matching analyses is to deal with undefined log ratios. If any reinforcer or response rate equals zero, the logarithm of the ratio is undefined: data are unsuitable for analyses. There have been some tentative solutions, but they had not been thoroughly investigated. The purpose of this article is to assess the adequacy of five treatments: omit undefined ratios, use full information maximum likelihood, replace undefined ratios by the mean divided by 100, replace them by a constant 1/10, and add the constant .50 to ratios. Based on simulations, the treatments are compared on their estimations of variance accounted for, sensitivity, and bias. The results show that full information maximum likelihood and omiting undefined ratios had the best overall performance, with negligibly biased and more accurate estimates than mean divided by 100, constant 1/10, and constant .50. The study suggests that mean divided by 100, constant 1/10, and constant .50 should be avoided and recommends full information maximum likelihood to deal with undefined log ratios in matching analyses.
Topics: Likelihood Functions; Animals; Data Interpretation, Statistical; Reinforcement, Psychology; Conditioning, Operant; Computer Simulation; Humans; Reinforcement Schedule
PubMed: 38837760
DOI: 10.1002/jeab.925 -
Journal of the Experimental Analysis of... Jul 2024We present a new methodology to partition different sources of behavior change within a selectionist framework based on the Price equation-the multilevel model of...
We present a new methodology to partition different sources of behavior change within a selectionist framework based on the Price equation-the multilevel model of behavioral selection. The multilevel model of behavioral selection provides a theoretical background to describe behavior change in terms of operant selection. Operant selection is formally captured by the covariance-based law of effect and accounts for all changes in individual behavior that involve a covariance between behavior and predictors of evolutionary fitness (e.g., food). In this article, we show how the covariance-based law of effect may be applied to different components of operant behavior (e.g., allocation, speed, and accuracy of responding), thereby providing quantitative estimates for various selection effects affecting behavior change using data from a published learning experiment with pigeons.
Topics: Conditioning, Operant; Animals; Columbidae; Models, Psychological; Reinforcement, Psychology; Choice Behavior
PubMed: 38825891
DOI: 10.1002/jeab.924 -
Behavioural Brain Research May 2024The study introduced and evaluated learning paradigms for Maylandia callainos cichlids using a modified version of the rodent T-maze, filled with tank water (the...
The study introduced and evaluated learning paradigms for Maylandia callainos cichlids using a modified version of the rodent T-maze, filled with tank water (the "sunken" modification). Both male and female fish underwent training in two distinct conditioning paradigms. Firstly, simple operant conditioning involved placing a food reward in either the right or left compartment. Cichlids demonstrated the ability to purposefully find the bait within 6 days of training, with a persistent place preference lasting up to 6 days. Additionally, the learning dynamics varied with sex: female cichlids exhibited reduction in latency to visit the target compartment and consume the bait, along with a decrease in the number of errors 3 and 4 days earlier than males, respectively. Secondly, visually-cued operant conditioning was conducted, with a food reward exclusively placed in the yellow compartment, randomly positioned on the left or right side of the maze during each training session. Visual learning persisted for 10 days until reaction time improvement plateaued. Color preference disappeared after 4 consecutive check-ups, with no sex-related interference. For further validation of visually-cued operant conditioning paradigm, drugs MK-801 (dizocilpine) and caffeine, known to affect performance in learning tasks, were administered intraperitoneally. Chronic MK-801 (0.17 mg/kg) impaired maze learning, resulting in no color preference development. Conversely, caffeine administration enhanced test performance, increasing precision in fish. This developed paradigm offers a viable approach for studying learning and memory and presents an effective alternative to rodent-based drug screening tools, exhibiting good face and predictive validity.
PubMed: 38825022
DOI: 10.1016/j.bbr.2024.115077