Nest building is an innate behavior in male and female rodents, even when raised in laboratory settings. As such, many researchers provide rodents synthetic and/or natural materials (such as twine, tissue, cotton, paper, and hay) as a gauge of their overall well-being and as an ancillary assessment to predict the possible decline in cognition. Typically, changes in nesting behaviors, such as failure to create a nest, indicate a change in health or welfare. In addition, nesting behavior is sensitive to many environmental and physiological challenges, as well as many genetic mutations underlying pathological disease states. The following protocol describes a nesting behavior paradigm that explores the usage of four types of nesting material. In addition, the protocol utilizes intraclass correlations to demonstrate that inter-rater reliability is higher when nests are constructed out of shredded paper compared to other common nesting materials such as cotton squares, paper twists, and soft cob bedding. The chosen methodology and statistical considerations (i.e., intraclass correlation) for this assay may be of interest for those conducting experiments assessing the quality of living of mice.

No abstract

Nest building is an innate behavior in male and female rodents, even when raised in laboratory settings. As such, many researchers provide rodents synthetic and/or natural materials (such as twine, tissue, cotton, paper, and hay) as a gauge of their overall well-being and as an ancillary assessment to predict the possible decline in cognition. Typically, changes in nesting behaviors, such as failure to create a nest, indicate a change in health or welfare. In addition, nesting behavior is sensitive to many environmental and physiological challenges, as well as many genetic mutations underlying pathological disease states. The following protocol describes a nesting behavior paradigm that explores the usage of four types of nesting material. In addition, the protocol utilizes intraclass correlations to demonstrate that inter-rater reliability is higher when nests are constructed out of shredded paper compared to other common nesting materials such as cotton squares, paper twists, and soft cob bedding. The chosen methodology and statistical considerations (i.e., intraclass correlation) for this assay may be of interest for those conducting experiments assessing the quality of living of mice.

Severe early life stress has long been associated with neuropsychological disorders in adulthood, including depression, schizophrenia, post-traumatic stress disorder, and memory dysfunction. To some extent, all of these conditions involve dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and reduced negative feedback inhibition of cortisol release in adulthood. However, the time course for mental health and hormonal outcomes across life stages and the attributes of early life stress that direct the behavioral and biological alterations is not fully understood. We designed our studies to compare outcomes of the two most common maternal deprivation schedules on cognitive ability prior to adulthood. We exposed rat pups to daily or randomly spaced maternal separation bouts within the first 3 weeks of life and examined cognitive performance, neurotrophic signaling, and stress and immune system markers during puberty. We found that the daily separation schedule impaired spatial learning while the randomly spaced schedule did not alter maze performance relative to normally reared control animals. Animals that underwent daily separation showed a tendency for reduced body weight compared to the randomly spaced condition, but there were no differences in adrenal weight. Thymus weight normalized by body weight was increased following daily separation compared to random separation and control conditions. Plasma corticosterone levels measured after behavior testing did not differ amongst experimental groups and there was no impact of TrKB receptor inhibition. Combined, the results show that different early life stress schedules produce different behavioral and biological outcomes when measured at puberty. Combined with prior findings from more mature animals, the results presented here suggest that daily neonatal stress produces varied alterations in spatial cognition at different life stages with a transient learning deficit at puberty preceding a more persistent and a progressive memory impairment through adulthood and into aging.

Neural circuits in mammalian brains consist of large numbers of different cell types having different functional properties. To better understand the separate roles of individual neuron types in specific aspects of spatial learning and memory, we perturbed the function of principal neurons in vivo during maze performance or in hippocampal slices during recording of evoked excitatory synaptic potentials. Transgenic mice expressing the Drosophila allatostatin receptor (AlstR) in cortical and hippocampal pyramidal cells were tested on an elevated plus maze, in a Y-maze, and in the Morris water maze. Relative to a control cohort, AlstR-positive mice treated with allatostatin exhibited no difference in open arm dwell time on the elevated plus maze or total number of arm entries in a Y-maze, but displayed reduced spontaneous alternation. When animals received massed or spaced training trials in the Morris water maze, and the peptide was delivered prior to an immediate probe, no effects on performance were observed. When the peptide was delivered during a probe trial performed 24 h after seven days of spaced training, allatostatin delivery to AlstR positive mice enhanced direct navigation to the escape platform. Combined, these results suggest that cortical and hippocampal pyramidal neurons are required during spatial decisionmaking in a novel environment and compete with other neural systems after extended training in a long-term reference memory task. In hippocampal slices collected from AlstR positive animals, allatostatin delivery produced frequency dependent alterations in the Schaffer collateral fiber volley (attenuated accommodation at 100 Hz) and excitatory postsynaptic potential (attenuated facilitation at 5 Hz). Combined, the neural and behavioral discoveries support the involvement of short-term plasticity of Schaffer collateral axons and synapses during exploration of a novel environment and during initial orientation to a goal in a well-learned setting.