Theory of Visual Attention (TVA) applied to mice in the 5-choice serial reaction time task

Fitzpatrick, Ciarán Martin; Caballero-Puntiverio, Maitane; Gether, Ulrik; Habekost, Thomas; Bundesen, Claus; Vangkilde, Signe; Andreasen, Jesper T.; Petersen, Anders

doi:10.1007/s00213-016-4520-6

Cited by 13 publications

(9 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Food-restricted mice were trained in modified nine-hole operant touchscreen-based chambers (40 × 34 × 42 cm; Campden Instruments) to reach high baseline performance at a 1.5-s stimulus duration probe in the 5-CSRTT as described elsewhere ( Caballero-Puntiverio et al, 2017 ; Fitzpatrick et al, 2017 ). Then, mice were injected with hM4Di and allowed to recover for 3 wk before motivational aspects of reward were assessed in the must-touch stage.…”

Section: Methodsmentioning

confidence: 99%

Locomotor- and Reward-Enhancing Effects of Cocaine Are Differentially Regulated by Chemogenetic Stimulation of Gi-Signaling in Dopaminergic Neurons

Runegaard

Sørensen

Fitzpatrick

et al. 2018

eNeuro

View full text Add to dashboard Cite

Dopamine plays a key role in the cellular and behavioral responses to drugs of abuse, but the implication of metabotropic regulatory input to dopaminergic neurons on acute drug effects and subsequent drug-related behavior remains unclear. Here, we used chemogenetics [Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)] to modulate dopamine signaling and activity before cocaine administration in mice. We show that chemogenetic inhibition of dopaminergic ventral tegmental area (VTA) neurons differentially affects locomotor and reward-related behavioral responses to cocaine. Stimulation of Gi-coupled DREADD (hM4Di) expressed in dopaminergic VTA neurons persistently reduced the locomotor response to repeated cocaine injections. An attenuated locomotor response was seen even when a dual-viral vector approach was used to restrict hM4Di expression to dopaminergic VTA neurons projecting to the nucleus accumbens. Surprisingly, despite the attenuated locomotor response, hM4Di-mediated inhibition of dopaminergic VTA neurons did not prevent cocaine sensitization, and the inhibitory effect of hM4Di-mediated inhibition was eliminated after withdrawal. In the conditioned place-preference paradigm, hM4Di-mediated inhibition did not affect cocaine-induced place preference; however, the extinction period was extended. Also, hM4Di-mediated inhibition had no effect on preference for a sugar-based reward over water but impaired motivation to work for the same reward in a touchscreen-based motivational assay. In addition, to support that VTA dopaminergic neurons operate as regulators of reward motivation toward both sugar and cocaine, our data suggest that repeated cocaine exposure leads to adaptations in the VTA that surmount the ability of Gi-signaling to suppress and regulate VTA dopaminergic neuronal activity.

show abstract

Section: Methodsmentioning

confidence: 99%

Locomotor- and Reward-Enhancing Effects of Cocaine Are Differentially Regulated by Chemogenetic Stimulation of Gi-Signaling in Dopaminergic Neurons

Runegaard

Sørensen

Fitzpatrick

et al. 2018

eNeuro

View full text Add to dashboard Cite

show abstract

“…This lack of difference in performance during single cue-length blocks or omissions strongly suggests that observed differences on the AET are specific to increases in attentional load rather than an effect of the loss of Scn8a on visual perception or discrimination. There was no effect of group on reaction time (seconds between cue termination and port selection), however all mice had increased reaction time for incorrect trials, which has also been correlated with impaired attention in other paradigms (Weissberg et al 1990, Fitzpatrick et al 2017) (Fig. 1E).…”

Section: Resultsmentioning

confidence: 77%

Prefrontal PV interneurons facilitate attention and are linked to attentional dysfunction in a mouse model of absence epilepsy

Ferguson

Huguenard

2022

Preprint

View full text Add to dashboard Cite

Absence seizures are characterized by brief periods of unconsciousness accompanied by a lapse in motor function that can occur hundreds of times throughout the day. Outside of these frequent moments of unconsciousness, approximately a third of patients experience treatment-resistant attention impairments. Convergent evidence suggests prefrontal cortex (PFC) dysfunction may underlie attention impairments in affected patients. To test this, we use a combination of slice physiology, fiber photometry, optogenetics, and behavior in the Scn8a+/- mouse model of absence epilepsy. In these mice, we find decreased parvalbumin interneuron (PVIN) recruitment in the medial PFC (mPFC) in vitro and hypoactivity during cue presentation in vivo that is linked to attention dysfunction. Further, we find that low levels of mPFC PVIN activity are predictive of poorer performance in WT littermates. This highlights cue-evoked PVIN activity as an important mechanism for attention and suggests PVINs may represent a therapeutic target for cognitive co-morbidities in absence epilepsy.

show abstract

“…Based on the framework of human TVA (Bundesen 1998;Bundesen and Harms 1999;Bundesen et al 2005;Habekost 2015) and the recently developed TVA model for mouse 5CSRTT (Fitzpatrick et al 2017), we developed a four-parameter TVA model adapted to the rat 5CSRTT. This makes it possible, for the first time, to estimate visual perceptual processing speed independent of motor reaction times from rat 5CSRTT data.…”

Section: Tva Modelling Of 5-csrtt Data (Tva-5csrtt)mentioning

confidence: 99%

“…In this mathematical model, a set of simple equations describes visual attention mechanisms, including processing speed of visual perceptual categorisations, which is a measure of attentional processing independent of motor reaction time (Bundesen 1990;Habekost and Starrfelt 2009;Bundesen et al 2015). To enable translational studies on attention, the TVA model was recently adapted to model effects of the anti-cholinergic drug scopolamine in mice in a 5-choice serial reaction time task (5CSRTT) (Fitzpatrick et al 2017)-a well-established task used to assess attention and impulsivity in rodents (Robbins 2002). We now adapt the TVA model to the rat 5CSRTT to study dopaminergic and noradrenergic modulation of attentional processing capacity in rats.…”

Section: Introductionmentioning

confidence: 99%

Theory of visual attention (TVA) applied to rats performing the 5-choice serial reaction time task: differential effects of dopaminergic and noradrenergic manipulations

et al. 2022

View full text Add to dashboard Cite

Rationale Attention is compromised in many psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). While dopamine and noradrenaline systems have been implicated in ADHD, their exact role in attentional processing is yet unknown. Objectives We applied the theory of visual attention (TVA) model, adapted from human research, to the rat 5-choice serial reaction time task (5CSRTT) to investigate catecholaminergic modulation of visual attentional processing in healthy subjects of high- and low-attention phenotypes. Methods Rats trained on the standard 5CSRTT and tested with variable stimulus durations were treated systemically with noradrenergic and/or dopaminergic agents (atomoxetine, methylphenidate, amphetamine, phenylephrine and atipamezole). TVA modelling was applied to estimate visual processing speed for correct and incorrect visual perceptual categorisations, independent of motor reaction times, as measures of attentional capacity. Results Atomoxetine and phenylephrine decreased response frequencies, including premature responses, increased omissions and slowed responding. In contrast, methylphenidate, amphetamine and atipamezole sped up responding and increased premature responses. Visual processing speed was also affected differentially. Atomoxetine and phenylephrine slowed, whereas methylphenidate and atipamezole sped up, visual processing, both for correct and incorrect categorisations. Amphetamine selectively improved visual processing for correct, though not incorrect, responses in high-attention rats only, possibly reflecting improved attention. Conclusions These data indicate that the application of TVA to the 5CSRTT provides an enhanced sensitivity to capturing attentional effects. Unexpectedly, we found overall slowing effects, including impaired visual processing, following drugs either increasing extracellular noradrenaline (atomoxetine) or activating the α1-adrenoceptor (phenylephrine), while also ameliorating premature responses (impulsivity). In contrast, amphetamine had potential pro-attentional effects by enhancing visual processing, probably due to central dopamine upregulation.

show abstract

Theory of Visual Attention (TVA) applied to mice in the 5-choice serial reaction time task

Abstract: This study shows for the first time how 5-CSRTT performance in mice can be mathematically modelled to yield estimates of attentional capacity that are directly comparable to estimates from human studies.

Cited by 13 publications

References 55 publications

Locomotor- and Reward-Enhancing Effects of Cocaine Are Differentially Regulated by Chemogenetic Stimulation of Gi-Signaling in Dopaminergic Neurons

Locomotor- and Reward-Enhancing Effects of Cocaine Are Differentially Regulated by Chemogenetic Stimulation of Gi-Signaling in Dopaminergic Neurons

Prefrontal PV interneurons facilitate attention and are linked to attentional dysfunction in a mouse model of absence epilepsy

Theory of visual attention (TVA) applied to rats performing the 5-choice serial reaction time task: differential effects of dopaminergic and noradrenergic manipulations

Contact Info

Product

Resources

About