Timing behavior in genetic murine models of neurological and psychiatric diseases

Karson, Ayşe; Balcı, Fuat

doi:10.1007/s00221-020-06021-4

Cited by 4 publications

(4 citation statements)

References 139 publications

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“…Second-level timing systems, the fundamental machinery for timekeeping in the brain, are associated with various cognitive functions, including foraging, associative learning, and decision making (Karson and Balcı 2021 ). Furthermore, interval timing perception is impaired in various neurological and psychiatric disorders, such as Parkinson’s disease, substance misuse, attention deficit hyperactivity disorder, and schizophrenia (Pastor et al 1992 ; Wittmann et al 2007 ; Noreika et al 2013 ; Snowden and Buhusi 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Core clock gene, Bmal1 , is required for optimal second-level interval production

Kim,

Choe

2023

Animal Cells and Systems

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Perception and production of second-level temporal intervals are critical in several behavioral and cognitive processes, including adaptive anticipation, motor control, and social communication. These processes are impaired in several neurological and psychological disorders, such as Parkinson’s disease and attention-deficit hyperactivity disorder. Although evidence indicates that second-level interval timing exhibit circadian patterns, it remains unclear whether the core clock machinery controls the circadian pattern of interval timing. To investigate the role of core clock molecules in interval timing capacity, we devised a behavioral assay called the interval timing task to examine prospective motor interval timing ability. In this task, the mouse produces two separate nose pokes in a pretrained second-level interval to obtain a sucrose solution as a reward. We discovered that interval perception in wild-type mice displayed a circadian pattern, with the best performance observed during the late active phase. To investigate whether the core molecular clock is involved in the circadian control of interval timing, we employed Bmal1 knockout mice (BKO) in the interval timing task . The interval production of BKO did not display any difference between early and late active phase, without reaching the optimal interval production level observed in wild-type. In summary, we report that the core clock gene Bmal1 is required for the optimal performance of prospective motor timing typically observed during the late part of the active period.

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Section: Discussionmentioning

confidence: 99%

Core clock gene, Bmal1 , is required for optimal second-level interval production

Kim,

Choe

2023

Animal Cells and Systems

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“…Here, we compare timing behavior using a task novel to the SHR/NCrl literature addressing timing in the model: the fixed‐interval (FI) temporal bisection task (Platt & Davis, 1983). The FI bisection task (sometimes called the “switch task”) has been used with great success to characterize timing in comparative and translational research using humans and nonhumans (Balci et al., 2008, 2009; Daniels et al., 2015; DeCoteau & Fox, 2022; Fox et al., 2016; Karson & Balcı, 2021). We compared SHR/NCrl, WKY/NCrl, and WI rats.…”

Section: Experiments 1: Timing In Shr/ncrl Wky/ncrl and Wi Strainsmentioning

confidence: 99%

“…Animal models provide additional control and a translational framework in order to better characterize and develop treatments for neurodevelopmental disorders like ADHD (Deane & Ward, 2022; Deane et al., 2017; DeCoteau & Fox, 2022; Fox, 2018; Karson & Balcı, 2021; Poulin & Fox, 2021; Soto, 2020). The spontaneously hypertensive rat from Charles River (SHR/NCrl) is one of the most widely used rodent models of ADHD‐HI and ADHD‐C (Sagvolden et al., 2005).…”

Section: Introductionmentioning

confidence: 99%

Timing and delay discounting in attention‐deficit/hyperactivity disorder: A translational approach

Fox,

Nicholson,

Singha

et al. 2023

Developmental Psychobiology

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Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that often presents with abnormal time perception and increased impulsive choice behavior. The spontaneously hypertensive rat (SHR) is the most widely used preclinical model of the ADHD-Combined and ADHD-Hyperactive/Impulsive subtypes of the disorder. However, when testing the spontaneously hypertensive rat from Charles River (SHR/NCrl) on timing and impulsive choice tasks, the appropriate control strain is not clear, and it is possible that one of the possible control strains, the Wistar Kyoto from Charles River (WKY/NCrl), is an appropriate model for ADHD-Predominately Inattentive. Our goals were to test the SHR/NCrl, WKY/NCrl, and Wistar (WI; the progenitor strain for the SHR/NCrl and WKY/NCrl) strains on time perception and impulsive choice tasks to assess the validity of SHR/NCrl and WKY/NCrl as models of ADHD, and the validity of the WI strain as a control. We also sought to assess impulsive choice behavior in humans diagnosed with the three subtypes of ADHD and compare them with our findings from the preclinical models. We found SHR/NCrl rats timed faster and were more impulsive than WKY/NCrl and WI rats, and human participants diagnosed with ADHD were more impulsive compared to controls, but there were no differences between the three ADHD subtypes.

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“…Traditionally, mouse models have been generated by introducing foreign genes into the nucleus of a fertilized egg or generating chimaeric mice using homologous recombination in embryonic stem (ES) cells (Capecchi, 2022;Doetschman et al, 1987;Thomas and Capecchi, 1987). For example, because 129-derived ES cells have been used the most to create genetically engineered mice, many studies investigating the effect of genetic manipulations on various behaviors (reviewed in Crawley et al, 1997), including interval timing (reviewed in Karson and Balcı, 2021) were performed in inbred 129, or 129 mixed-backgrounds.…”

Section: Introductionmentioning

confidence: 99%

Not All Mice Are Created Equal: Interval Timing Accuracy and Scalar Timing in 129, Swiss-Webster, and C57BL/6 Mice

Buhusi

Meyer

Oprisan

et al. 2022

Timing Time Percept.

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Many species, including humans, show both accurate timing − appropriate time estimation in the seconds to minutes range − and scalar timing − time estimation error varies linearly with estimated duration. Behavioral paradigms aimed at investigating interval timing are expected to evaluate these dissociable characteristics of timing. However, when evaluating interval timing in models of neuropsychiatric disease, researchers are confronted with a lack of adequate studies about the parent (background) strains, since accuracy and scalar timing have only been demonstrated for the C57BL/6 strain of mice (Buhusi, Aziz, Winslow, Carter, Swearingen, & Buhusi (2009) Behav. Neurosci., 123, 1102–1113). We used a peak-interval (PI) procedure with three intervals − a protocol in which other species, including humans, demonstrate accurate, scalar timing − to evaluate timing accuracy and scalar timing in three strains of mice frequently used in genetic and behavioral studies: 129, Swiss-Webster (SW), and C57BL/6. C57BL/6 mice showed accurate, scalar timing, while 129 and SW mice showed departures from accuracy and/or scalar timing. Results suggest that the genetic background/strain of the mouse is a critical variable for studies investigating interval timing in genetically engineered mice. Our study validates the PI procedure with multiple intervals as a proper technique, and the C57BL/6 strain as the most suitable genetic background to date for behavioral investigations of interval timing in genetically engineered mice modeling human disorders. In contrast, studies using mice in 129, SW, or mixed-background strains should be interpreted with caution, and thorough investigations of accuracy and scalar timing should be conducted before a less studied strain of mouse is considered for use in timing studies.

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Timing behavior in genetic murine models of neurological and psychiatric diseases

Cited by 4 publications

References 139 publications

Core clock gene, Bmal1 , is required for optimal second-level interval production

Core clock gene, Bmal1 , is required for optimal second-level interval production

Timing and delay discounting in attention‐deficit/hyperactivity disorder: A translational approach

Not All Mice Are Created Equal: Interval Timing Accuracy and Scalar Timing in 129, Swiss-Webster, and C57BL/6 Mice

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