Visual cortical neurons fire at higher rates to visual stimuli during locomotion than during immobility, while maintaining orientation selectivity. The mechanisms underlying this change in gain are not understood. We performed whole-cell recordings from layer 2/3 and layer 4 visual cortical excitatory neurons and from parvalbumin-positive and somatostatin-positive inhibitory neurons in mice that were free to rest or run on a spherical treadmill. We found that the membrane potential of all cell types became more depolarized and (with the exception of somatostatin-positive interneurons) less variable during locomotion. Cholinergic input was essential for maintaining the unimodal membrane potential distribution during immobility, whereas noradrenergic input was necessary for the tonic depolarization associated with locomotion. Our results provide a mechanism for how neuromodulation controls the gain and signal-to-noise ratio of visual cortical neurons during changes in the state of vigilance.

https://escholarship.org/content/qt93n7s9k5/qt93n7s9k5.pdf?t=qaf2l2

Cellular mechanisms of brain state-dependent gain modulation in visual cortex.

Factors influencing behavior in the forced swim test.

Acetylcholine and attention.

Transgenic Tg2576 mice overexpressing human amyloid precursor protein (hAPP) are a widely used Alzheimer's disease (AD) mouse model to evaluate treatment effects on amyloid beta (Aβ) pathology and cognition. Tg2576 mice on a B6;SJL background strain carry a recessive rd1 mutation that leads to early retinal degeneration and visual impairment in homozygous carriers. This can impair performance in behavioral tests that rely on visual cues, and thus, affect study results. Therefore, B6;SJL/Tg2576 mice were systematically backcrossed with 129S6/SvEvTac mice resulting in 129S6/Tg2576 mice that lack the rd1 mutation. 129S6/Tg2576 mice do not develop retinal degeneration but still show Aβ accumulation in the brain that is comparable to the original B6;SJL/Tg2576 mouse. However, comprehensive studies on cognitive decline in 129S6/Tg2576 mice are limited. In this study, we used two dementia mouse models on a 129S6 background--scopolamine-treated 129S6/SvEvTac mice (3-5 month-old) and transgenic 129S6/Tg2576 mice (11-13 month-old)-to establish a behavioral test battery for assessing learning and memory. The test battery consisted of five tests to evaluate different aspects of cognitive impairment: a Y-Maze forced alternation task, a novel object recognition test, the Morris water maze, the radial arm water maze, and a Y-maze spontaneous alternation task. We first established this behavioral test battery with the scopolamine-induced dementia model using 129S6/SvEvTac mice and then evaluated 129S6/Tg2576 mice using the same testing protocol. Both models showed distinctive patterns of cognitive impairment. Together, the non-invasive behavioral test battery presented here allows detecting cognitive impairment in scopolamine-treated 129S6/SvEvTac mice and in transgenic 129S6/Tg2576 mice. Due to the modular nature of this test battery, more behavioral tests, e.g. invasive assays to gain additional cognitive information, can easily be added.

/pdf/a-comprehensive-behavioral-test-battery-to-assess-learning-44tobhn8ev.pdf

A Comprehensive Behavioral Test Battery to Assess Learning and Memory in 129S6/Tg2576 Mice.

Judgment bias tasks (JBTs) are considered as a family of promising tools in the assessment of emotional states of animals. JBTs provide a cognitive measure of optimism and/or pessimism by recording behavioral responses to ambiguous stimuli. For instance, a negative emotional state is expected to produce a negative or pessimistic judgment of an ambiguous stimulus, whereas a positive emotional state produces a positive or optimistic judgment of the same ambiguous stimulus. Measuring an animal's emotional state or mood is relevant in both animal welfare research and biomedical research. This is reflected in the increasing use of JBTs in both research areas. We discuss the different implementations of JBTs with animals, with a focus on their potential as an accurate measure of emotional state. JBTs have been successfully applied to a very broad range of species, using many different types of testing equipment and experimental protocols. However, further validation of this test is deemed necessary. For example, the often extensive training period required for successful judgment bias testing remains a possible factor confounding results. Also, the issue of ambiguous stimuli losing their ambiguity with repeated testing requires additional attention. Possible improvements are suggested to further develop the JBTs in both animal welfare and biomedical research.

/pdf/making-decisions-under-ambiguity-judgment-bias-tasks-for-16tvrdi6k9.pdf

Making Decisions under Ambiguity : Judgment Bias Tasks for Assessing Emotional State in Animals

The validity of scopolamine as a pharmacological model for cognitive impairment: A review of animal behavioral studies

A systematic review of social support interventions for caregivers of people with dementia: Are they doing what they promise?

https://pure.mpg.de/pubman/item/item_3219251_1/component/file_3219256/Blokland_etal_2012_Use%20of%20test%20battery%20assessing%20affective%20behavior%20in%20rats.pdf

The use of a test battery assessing affective behavior in rats: order effects.

Rationale
The nonselective muscarinic antagonist scopolamine hydrobromide (SCOP) is employed as the gold standard for inducing memory impairments in healthy humans and animals. However, its use remains controversial due to the wide spectrum of behavioral effects of this drug.

/pdf/a-comparison-of-scopolamine-and-biperiden-as-a-rodent-model-35cyskfegf.pdf

Inge Klinkenberg

Papers

The validity of scopolamine as a pharmacological model for cognitive impairment: A review of animal behavioral studies

Acetylcholine and attention.

A systematic review of social support interventions for caregivers of people with dementia: Are they doing what they promise?

The use of a test battery assessing affective behavior in rats: order effects.

A comparison of scopolamine and biperiden as a rodent model for cholinergic cognitive impairment.