Suitability of the New Frontier Task Across Mouse Housing Population Sizes

Amotivation is a major symptom of several psychiatric disorders. However, which specific motivations are most affected in various illnesses is not well understood. In major depressive disorder (MDD), anecdotal evidence suggests the motivation to explore may be especially affected, but direct evidence from either patients or animal models is lacking. To investigate the potential for, and nature of, exploratory drive deficits in MDD, we subjected mice to a chronic social defeat (CSD) manipulation that gives rise to a MDD-like behavioural ensemble, and performed a behavioural battery to examine bodyweight homeostasis, ambulation, anxiety, exploratory behaviour motivated by either novelty or fear, and short-term memory. Consistent with previous reports, we found a disruption of bodyweight homeostasis and reduced ambulation following CSD treatment, but we found no evidence for anxiogenic effects or impairments in short-term memory. Surprisingly, we also observed profoundly delayed and diminished exploration of novel, safe space following CSD, while exploration motivated by fear remained intact. These results extend our knowledge of the behavioural phenotypes in mice resulting from CSD by homing in on specific motivational drives. In MDD patients, reduced exploration could compound disease symptomatology by preventing engagement in what could be rewarding exploration experiences, and targeting deficits in the motivation to explore may represent a novel avenue for treatment.

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Selective amotivation deficits following chronic psychosocial stress in mice

Cabal

Ioanas

Seifritz

et al. 2017

Behavioural Brain Research

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A Dual Effect of Dopamine on Hippocampal LTP and Cognitive Functions in Control and Kindled Mice

Ahmadi,

Rouhi,

Fathollahi

et al. 2023

J. Neurosci.

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The impact of dopamine on synaptic plasticity and cognitive function following seizure is not well understood. Here, using optogenetics in the freely-behaving animal, we examined exploratory behavior and short-term memory in control and kindled male mice during tonic stimulation of dopaminergic neurons within the ventral tegmental area (VTA). Furthermore, using field potential recording, we compared the effect of dopamine on synaptic plasticity in stratum radiatum and stratum oriens layers of both ventral and dorsal hippocampal CA1 regions, and again in both control and kindled male mice. Our results demonstrate that tonic stimulation of VTA dopaminergic neurons enhances novelty-driven exploration and short-term spatial memory in kindled mice, essentially rescuing the seizure-induced cognitive impairment. In addition, we found that dopamine has a dual effect on LTP in control versus kindled mice, such that application of dopamine prevented LTP induction in slices from control mice, but rescued LTP in slices taken from the kindled animal. Taken together, our results highlight the potential for dopaminergic modulation in improving synaptic plasticity and cognitive function following seizure.Significance StatementMemory deficit in epilepsy is a major medical issue. While some progress has been made in describing the underlying synaptic abnormalities that likely underlie memory deficit in epilepsy, less progress has been made in identifying treatment options. Recently, we demonstrated that in addition to memory deficit, occurrence of kindled seizures in mice is also associated with a decreased motivation to explore novel spatial environments. Here we show that optogenetic manipulation of dopaminergic circuitry underlying exploratory drive in kindled mice rescues the associated dysfunction within i) hippocampal synaptic plasticity, ii) novelty-driven exploration, and iii) spatial memory, indicating pharmacological and behavioral therapies that influence dopaminergic signaling may be useful in addressing cognitive impairment associated with epilepsy.

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Suitability of the New Frontier Task Across Mouse Housing Population Sizes

Cited by 2 publications

References 8 publications

Selective amotivation deficits following chronic psychosocial stress in mice

Selective amotivation deficits following chronic psychosocial stress in mice

A Dual Effect of Dopamine on Hippocampal LTP and Cognitive Functions in Control and Kindled Mice

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