Epilepsy or epileptic syndromes affect more than 70 million people, often comorbid with autism spectrum disorders (ASD). Seizures are concerned as a factor for social regression in ASD. A stepwise experimental approach to this problem requires an animal model to provoke seizures and monitor subsequent behavior. We used rats of the Krushinsky–Molodkina (KM) strain as a validated inbred genetic model for human temporal lobe epilepsy, with recently described social deficiency and hypolocomotion. Generalized tonic-clonic seizures in KM rats are sound-triggered, thus being controlled events in drug-naïve animals. We studied whether seizure experience would aggravate contact deficits in these animals. Locomotor and contact parameters were registered in “the elevated plus maze”, “socially enriched open field”, and “social novelty/social preference tests” before and after sound-provoked seizures. The triple seizure provocations minimally affected the contact behavior. The lack of social drive in KM rats was not accompanied by a submissive phenotype, as tested in “the tube dominance test”, but featured with a poor contact repertoire. Here, we confirmed our previous findings on social deficits in KM rats. The contact deficiency was dissociated from hypolocomotion and anxiety and did not correlate with seizure experience. It was established that experience of rare, generalized tonic-clonic convulsions did not lead to an impending regress in contact motivation, as seen in an animal model of genetic epilepsy and comorbid social deficiency. One of the oldest animal models for epilepsy has a translational potential to study mechanisms of social behavioral deficits in future neurophysiological and pharmacological research.
We examined sex differences in behavioral responses to fear-related learning through ultrasonic vocalization. Adult male and female rats of two inbred rat strains (WAG/Rij rats with genetic predisposition absence epilepsy, n = 25; and the minor substrain NEW with non-epileptic phenotype, n = 32) were examined in the two-way active avoidance task (50 trials). Three behavioral responses were defined: successful learning, unsuccessful learning, and freezing (motionless behavior). We found that males were more likely to experience freezing (40%) than females (3.7%). Females performed significantly better than males: 93% of females showed “successful learning”, while only 43.2% of males did. Long-lasting 22 kHz ultrasonic calls, so-called aversive ultrasonic vocalizations aUSVs, were recorded in 26% of females (only successful learners) and in 50% of males. The density of aUSVs in females was lower than in males. WAG/Rij males performed much poorer than the NEW males. In general, males, in contrast to females, showed significantly poorer avoidance learning, more frequently experienced freezing, and produced more aversive USVs. Males thus experienced a negative emotional state, rather than exhibiting poor cognitive abilities. Perhaps, WAG/Rij rats and a minor NEW substrain showed an increased emotionally in fear-related tasks, because they are prone to emotional disorders or emotional exhaustion. Sex differences in freezing and in aUSVs might result from the poorly understood neuromodulatory effects of the cholinergic system.
Objectives: Animal models of human diseases are commonly used in experimental research. Autism Spectrum Disorder (ASD) is characterized by reduced social motivation and often co-occurs with epilepsy, representing a distinct clinical subgroup. This study investigated social deficits in Krushinsky-Molodkina (KM) rats, which present with latent epilepsy and an autistic-like phenotype, by measuring ultrasonic communications during social interaction. Methods: The three-chamber test for social preference/novelty, accompanied by registration of ultrasonic vocalizations (USVs), was conducted in 12 KM and 12 control Wistar rats. For analysis, each individual vocalization trajectory was mapped and the results were derived from aggregating the individual data. To assess potential anhedonia, sucrose preference was tested in a separate group (10 KM and 20 Wistar rats) by measuring the consumption of 1% sucrose and water in individual rats over a 24-h period. All animals used were seizure-naive males, aged 4–6 months. Results: A longer duration of aversive USV calls was registered during the sociability tests in KM rats (p < 0.05, compared with controls). The majority (p < 0.05) of aversive USVs occurred when KM rats distanced themselves from the social stimuli, and the duration of these calls showed a positive correlation with freezing behavior (Spearman coefficient Rs = 0.68, p < 0.05). Reduced sucrose preference was not observed in KM rats; instead, an increase in daytime sucrose consumption was noted. Conclusions: KM rats exhibit negative emotional states in sociability tests, as evidenced by enhanced aversive vocalizations and distancing behavior. The social aversion observed in KM rats is not associated with anhedonia.
Background/Objectives: The vibrotactile system, which is essential for guiding behavior in nocturnal rodents such as mice and rats, provides critical sensory input. To investigate the role of vibrotactile sensory inflow in neonatal locomotion, we used previsual rat pups that underwent bilateral vibrissectomy. Subsequently, their motor behavior was evaluated in an open field test. Methods: A total of 42 previsual pups from four litters were assigned to either bilateral vibrissectomy or sham surgery groups on postnatal days (PND) 9–12, with group allocation balanced across litters. Results: Open-field testing on PND 13 revealed that while vibrissectomy (VE) did not affect gross locomotor activity—such as distance traveled, speed, acceleration, or freezing episodes (all >0.05)—it significantly altered spatial behavior. To quantify spatial patterns of curvy tracks, we analyzed trajectorial compaction within the central zone, lacking the tactile guidance of the walls: trajectories were smoothed using virtual coatings scaled to the vibrissal length (16 mm). For each track, an individual linearized reference path was generated and subjected to identical smoothing. The compaction ratio—calculated as the coated area of the smoothed linearized reference divided by the coated area of the experimental track—was significantly greater in VE pups than in sham controls (p = 0.03). This effect was not attributable to differences in the path length traveled within the central zone. The increased compaction persisted when the smoothing scale was increased 2–3 fold (32–64 mm radii, approximating the pups’ mean body size), but not at smaller scales (2–4 mm). Conclusions: These results demonstrate that tactile input specifically modulates the spatial, rather than locomotor, components of nonvisual navigation. Consequently, the track compaction may serve as a sensitive marker for assessing vibrotactile function in developing laboratory rodents.
The vibrotactile system provides essential sensory input for early behavior in previsual rat pups. To examine its role in spatial navigation, we conducted bilateral vibrissectomy or sham procedures on postnatal day (PND) 9–12 in 42 previsual pups (4 litters, balanced groups). Open-field testing on PND 13 showed that while vibrissectomy (VE) did not alter gross locomotor parameters (distance traveled, speed, acceleration, or freezing episodes; all p > 0.05), it significantly modified spatial behavior. VE pups explored a smaller percentage of the arena area (p = 0.01). We analyzed trajectorial compaction in the central zone (lacking wall tactile support) by smoothing trajectories with virtual coatings scaled to vibrissal length (16 mm). Individual references were generated for each track through linearization and identical smoothing. The compaction ratio, calculated as the ratio between the coated areas of linearized reference and experimental tracks, was significantly higher VE pups compared to sham controls (p = 0.03). No significant group difference was observed in path lengths within the central zone. This effect persisted when smoothing scales increased 2–3 fold (32–64 mm radii, approximating body size), but not at smaller scales (2–4 mm). These findings indicate that vibrissal input regulates spatial rather than locomotor components of previsual behavior. The simple open-field measures (area coverage, track compaction) thus serve as sensitive biomarkers for assessing vibrissal function in developing rodents. This study underscores the organizational role of tactile inputs in early spatial navigation and establishes a translatable hallmark for investigating sensory-guided behavior in neurodevelopment.