K369I Tau Mice Demonstrate a Shift Towards Striatal Neuron Burst Firing and Goal-directed Behaviour

Mo, Max; Jönsson, Marie E.; Mathews, Miranda A.; Johnstone, Daniel M.; Ke, Yazi D.; Ittner, Lars M.; Balleine, Bernard W.; Furlong, Teri M.; Camp, Aaron J.

doi:10.1016/j.neuroscience.2020.09.023

Cited by 3 publications

(4 citation statements)

References 95 publications

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“…However, we suggest caution in interpreting this as evidence that neuroinflammation "improved" goal-directed control. Indeed, when a similar result was demonstrated in the K3691 tau mouse model of Alzheimer's disease 59 the authors suggested that, rather than improving behaviour, the transgenic manipulation had impaired development of habits relative to controls. A similar interpretation could be applied to current results, because habitual responding on devaluation tests produces performance that is identical to that exhibited by male and female shams on the Day-4 test in the current study (i.e.…”

Section: The Acceleration In Goal-directed Action Control Does Not In...mentioning

confidence: 82%

Hippocampal neuroinflammation causes sex-specific disruptions in action selection, food approach memories, and neuronal excitation

Ganesan,

Ghorbanpour,

Kendall

et al. 2024

Preprint

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Hippocampal neuroinflammation is present in multiple diseases and disorders that impact motivated behaviour in a sex-specific manner, but whether neuroinflammation alone is sufficient to disrupt such behaviour is unknown. We investigated this question here using mice. First, application of the endotoxin and neuroinflammatory mimetic Lipopolysaccharide (LPS) to primary hippocampal neurons alone did not alter their activity but triggered neuronal excitation in mixed neuronal/glial co- or tri-cultures, providing initial indications of the potential mechanism causing neuroinflammation and the associated behavioural change. We next demonstrated this directly, because intra-hippocampal administration of LPS disrupted both instrumental responding and Pavlovian approach in a sex-specific manner, whereas it enhanced goal-directed action control and locomotor activity consistently across sexes. Finally, we showed that although LPS elicited a similar neuroinflammatory response in male and female mice, it increased neuronal activation in females and decreased it in males, providing evidence of a sexually dimorphic effect.

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Section: The Acceleration In Goal-directed Action Control Does Not In...mentioning

confidence: 82%

Hippocampal neuroinflammation causes sex-specific disruptions in action selection, food approach memories, and neuronal excitation

Ganesan,

Ghorbanpour,

Kendall

et al. 2024

Preprint

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show abstract

“…For the first 3 days, lever pressing was continuously reinforced. Thereafter, the rate of reinforcement shifted to a random interval (RI) schedule where outcomes were delivered for the first lever press made after an average interval of 15 (RI15), 30 (RI30) or 60 (RI60) seconds in order to promote habitual behaviour (Bingul et al, 2022;Hadjas et al, 2019) and the other half received home chow (5 g) for 1 hour in distinct feeding cages located in a room different from where training had been conducted (Hadjas et al, 2019;Mo et al, 2020). The mice were then given a 5-minute extinction test where the lever was presented but no outcomes were delivered.…”

Section: Methodsmentioning

confidence: 99%

“…Tests were given after the last day of RI30 (early training), after day 5 of RI60 (mid training) and after day 12 of RI60 (late training). During outcome devaluation, half of the mice were given ad libitum access to pellets (5 g) and the other half received home chow (5 g) for 1 hour in distinct feeding cages located in a room different from where training had been conducted (Hadjas et al, 2019; Mo et al, 2020). The mice were then given a 5-minute extinction test where the lever was presented but no outcomes were delivered.…”

Section: Experiments 2: Habitual Behaviourmentioning

confidence: 99%

“…The mice were then given a 5-minute extinction test where the lever was presented but no outcomes were delivered. The same procedure was repeated 1 day later except that mice were given ad libitum access to the other outcome so that each mouse was tested under devalued and valued conditions in counter-balanced order (Mo et al, 2020). Mice that are habitual in their responding will press the lever equally under devalued and valued conditions (Hadjas et al, 2019; Mo et al, 2020).…”

Section: Experiments 2: Habitual Behaviourmentioning

confidence: 99%

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Immp2l knockdown increases stimulus-driven instrumental behaviour but does not alter goal-directed learning or neuron density in cortico-striatal circuits in a mouse model of Tourette syndrome and autism spectrum disorder

Leung

Merlin

Walker

et al. 2023

Preprint

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Cortico-striatal neurocircuits mediate goal-directed and habitual actions which are necessary for adaptive behaviour. It has recently been proposed that some of the core symptoms of autism spectrum disorder (ASD) and Gilles de la Tourette syndrome (GTS), such as tics and repetitive behaviours, may emerge because of imbalances in these neurocircuits. We have recently developed a model of ASD and GTS by knocking down Immp2l, a mitochondrial gene frequently associated with these disorders. The current study sought to determine whether Immp2l knockdown (KD) in male mice alters flexible, goal- or cue- driven behaviour using procedures specifically designed to examine response-outcome and stimulus-response associations, which underlie goal-directed and habitual behaviour, respectively. Whether Immp2l KD alters neuron density in cortico-striatal neurocircuits known to regulate these behaviours was also examined. Immp2l KD mice and wild type-like mice (WT) were trained on Pavlovian and instrumental learning procedures where auditory cues predicted food delivery and lever-press responses earned a food outcome. It was demonstrated that goal-directed learning was not changed for Immp2l KD mice compared to WT mice, as lever-press responses were sensitive to changes in the value of the food outcome, and to contingency reversal and degradation. There was also no difference in the capacity of KD mice to form habitual behaviours compared to WT mice following extending training of the instrumental action. However, Immp2l KD mice were more responsive to auditory stimuli paired with food as indicated by a non-specific increase in lever response rates during Pavlovian-to-instrumental transfer. Finally, there were no alterations to neuron density in striatum or any prefrontal cortex or limbic brain structures examined. Thus, the current study suggests that Immp2l is not necessary for learned maladaptive goal or stimulus driven behaviours in ASD or GTS, but that it may contribute to increased capacity for external stimuli to drive behaviour. Alterations to stimulus-driven behaviour could potentially influence the expression of tics and repetitive behaviours, suggesting that genetic alterations to Immp2l may contribute to these core symptoms in ASD and GTS. Given that this is the first application of this battery of instrumental learning procedures to a mouse model of ASD or GTS, it is an important initial step in determining the contribution of known risk-genes to goal-directed versus habitual behaviours, which should be more broadly applied to other rodent models of ASD and GTS in the future.

show abstract

Immp2l knockdown in male mice increases stimulus-driven instrumental behaviour but does not alter goal-directed learning or neuron density in cortico-striatal circuits in a model of Tourette syndrome and autism spectrum disorder

Leung

Merlin

Walker

et al. 2023

Behavioural Brain Research

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K369I Tau Mice Demonstrate a Shift Towards Striatal Neuron Burst Firing and Goal-directed Behaviour

Cited by 3 publications

References 95 publications

Hippocampal neuroinflammation causes sex-specific disruptions in action selection, food approach memories, and neuronal excitation

Hippocampal neuroinflammation causes sex-specific disruptions in action selection, food approach memories, and neuronal excitation

Immp2l knockdown increases stimulus-driven instrumental behaviour but does not alter goal-directed learning or neuron density in cortico-striatal circuits in a mouse model of Tourette syndrome and autism spectrum disorder

Immp2l knockdown in male mice increases stimulus-driven instrumental behaviour but does not alter goal-directed learning or neuron density in cortico-striatal circuits in a model of Tourette syndrome and autism spectrum disorder

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