Cognitive behavioral markers of neurodevelopmental trajectories in rodents

Abstract

Between adolescence and adulthood, the brain critically undergoes maturation and refinement of synaptic and neural circuits that shape cognitive processing. Adolescence also represents a vulnerable period for the onset of symptoms in neurodevelopmental psychiatric disorders. Despite the wide use of rodent models to unravel neurobiological mechanisms underlying neurodevelopmental disorders, there is a surprising paucity of rigorous studies focusing on normal cognitive-developmental trajectories in such models. Here, we sought to behaviorally capture maturational changes in cognitive trajectories during adolescence and into adulthood in male and female mice using distinct behavioral paradigms. C57 BL/6J mice (4.5, 6, and 12 weeks of age) were assessed on three behavioral paradigms: drug-induced locomotor hyperactivity, prepulse inhibition, and a novel validated version of a visuospatial paired-associate learning touchscreen task. We show that the normal maturational trajectories of behavioral performance on these paradigms are dissociable. Responses in drug-induced locomotor hyperactivity and prepulse inhibition both displayed a ‘U-shaped’ developmental trajectory; lower during mid-adolescence relative to early adolescence and adulthood. In contrast, visuospatial learning and memory, memory retention, and response times indicative of motivational processing progressively improved with age. Our study offers a framework to investigate how insults at different developmental stages might perturb normal trajectories in cognitive development. We provide a brain maturational approach to understand resilience factors of brain plasticity in the face of adversity and to examine pharmacological and non-pharmacological interventions directed at ameliorating or rescuing perturbed trajectories in neurodevelopmental and neuropsychiatric disorders.

Baseline prepulse inhibition dependency of orexin A and REM sleep deprivation

“…This is consistent with the literature and shows a clear impairment of OXA-induced modulation of the PPI response at P98. Our findings also agree with previous reports indicating that PPI response is elevated by age (Jafari et al 2020 ; Choy et al 2021 ). Together with the age-related changes in orexinergic system, the developmental changes on the PPI-related systems could also be one of the underlying mechanisms.…”

The Influence of Social Isolation on Social Orientation, Sociability, Social Novelty Preference, and Hippocampal Parvalbumin-Expressing Interneurons in Peripubertal Rats – Understanding the Importance of Meeting Social Needs in Adolescence

“…Although it is well known that between adolescence and adulthood the brain undergoes maturation and refinement of synaptic and neural circuits, there are few rigorous studies focusing on behavioral markers of neurodevelopmental trajectories in rodents ( Choy et al, 2021 ). Here, we show that, in typically developing early-to-mid-adolescent GH rats, social orientation (preference for social space) is absent while sociability (preference for social over object novelty) becomes evident at the end of mid-adolescence, strictly through participation in social contact (consummatory/liking) and not through the appetitive/wanting response.…”

Comprehensive Transcriptomic Investigation of Rett Syndrome Reveals Increasing Complexity Trends from Induced Pluripotent Stem Cells to Neurons with Implications for Enriched Pathways

“…Investigating such interactions in relation to brain structure and function provides great convenience in deciphering the mechanism of NDDs . Within this scope, the explanation of the genetic nature of NDDs and the study of behavioral outcomes associated with brain development are recapitulated by preclinical models that summarize normal maturation trajectories …”

“…2 Within this scope, the explanation of the genetic nature of NDDs and the study of behavioral outcomes associated with brain development are recapitulated by preclinical models that summarize normal maturation trajectories. 3 Rett syndrome (RTT), which was defined by Andreas Rett in 1966, is a rare NDD that mostly occurs in female patients, and is generally observed as a loss of hand-arm coordination, speech difficulties, irregular growth in the head structure, intestinal problems and respiratory irregularities. 4−6 More than 95% of classic RTT cases are caused by a mutation in the MECP2 gene, which is mostly expressed in the brain and responsible for the expression of thousands of genes.…”