Hybrid offspring of C57BL/6J mice exhibit improved properties for neurobehavioral research

Sloin, Hadas E.; Bikovski, Lior; Levi, Amir; Amber-Vitos, Ortal; Katz, Tomer; Spivak, Lidor; Someck, Shirly; Gattegno, Roni; Sivroni, Shir; Sjulson, Lucas

doi:10.1101/2022.05.03.490527

Cited by 3 publications

(3 citation statements)

References 72 publications

(83 reference statements)

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“…Unexpectedly, in contrast to our first experiment, both aged transgenic groups developed concatenated action sequences throughout instrumental training (Extended Data Fig. 9c-f), an effect that could be due to the improved behavioural performance in F1 hybrid strains (Sloin et al, 2022), supporting the notion that compromised action structure in ageing is a labile state that can be relatively easy to rescue through indirect interventions (Matamales et al, 2017) (e.g. Fig.…”

Section: Resultssupporting

confidence: 59%

Restoring functional D2- to D1-neuron correspondence enables goal-directed action control in long-lived striatal circuits

Bertran‐Gonzalez

Dinale

Matamales

2022

Preprint

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Multidisciplinary evidence suggests that instrumental performance is governed by two major forms of behavioural control: goal-directed and autonomous processes. Brain-state abnormalities affecting the striatum, such as ageing, often shift control towards autonomous - habit-like - behaviour, although the neural mechanisms responsible for this shift remain unknown. Here, combining instrumental conditioning with cell-specific functional mapping and manipulation in striatal neurons, we explored strategies that invigorate goal-directed action capacity in aged mice. In animals performing instrumental actions, D2- and D1-neurons of the aged striatum were engaged in a characteristically counterbalanced manner, something that related to the propensity to express autonomous behaviour. Long-lasting, cell-specific desensitisation of D2-neurons in aged transgenic mice recapitulated the uneven D2- to D1-neuron functional correspondence observed in young mice, an effect that enabled successful goal-directed action. Our findings contribute to the understanding of the neural bases of behavioural control and propose neural system interventions that enhance cognitive functioning in habit-prone brains.

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Section: Resultssupporting

confidence: 59%

Restoring functional D2- to D1-neuron correspondence enables goal-directed action control in long-lived striatal circuits

Bertran‐Gonzalez

Dinale

Matamales

2022

Preprint

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“…Additionally, an inbred genetic background limits the generalizability of genotype-phenotype relationships(55) and display highly heritable stain-specific phenotypes in brain volume, scalar diffusion tensor imaging metrics, and quantitative connectomes(56). Similarly, contrary to the assumed relationship, meta-analysis of coefficients of variation do not find evidence of greater trait stability in inbred mice than outbred mice, and hybrid mice show enhanced properties desired for neurobiological research such as reduced anxiety-like behavior, improved learning, and enhanced long-term spatial memory(57). Taken within the context of developing a resource whole brain atlas for incubation of food craving in mice, outbred populations likely provide a more generalizable and robust platform.…”

Section: Discussionmentioning

confidence: 99%

Incubation of palatable food craving is associated with brain-wide neuronal activation in mice

Madangopal

Szelenyi

Nguyen

et al. 2022

Preprint

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Studies using rodent models have shown that relapse to drug or food seeking increases progressively during abstinence, a phenomenon termed "incubation of craving". Mechanistic studies of incubation of craving have focused on specific neurobiological targets within pre-selected brain areas. Recent methodological advances in whole-brain immunohistochemistry, clearing, and imaging now enable unbiased brain-wide cellular resolution mapping of regions and circuits engaged during learned behaviors. However, these whole brain imaging approaches were developed for mouse brains while incubation of drug craving has primarily been studied in rats and incubation of food craving has not been demonstrated in mice. Here, we established a mouse model of incubation of palatable food craving and examined food reward seeking after 1, 15, and 60 abstinence days. We then used the neuronal activity marker Fos with intact brain mapping procedures to identify corresponding patterns of brain-wide activation. Relapse to food seeking was significantly higher after 60 abstinence days than after 1 or 15 days. Using unbiased ClearMap analysis, we identified increased activation of multiple brain regions, particularly corticostriatal structures, following 60, but not 15 abstinence days. We used orthogonal SMART2 analysis to confirm these findings within corticostriatal and thalamocortical subvolumes and applied expert-guided registration to investigate subdivision and layer-specific activation patterns. Overall, we (1) identified novel brain-wide activity patterns during incubation of food seeking using complementary analytical approaches, and (2) provide a single-cell resolution whole-brain atlas that can be used to identify functional networks and global architecture underlying incubation of food craving.

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“…Experiments were conducted using C57BL/6J x FVB F1 hybrid mice (38). For the visual stimulation task, we chronically implanted a 64-site silicon probe (NeuroNexus) in the primary visual cortex (V1) (AP: 3.4 ML: 2.6 DV: 0.6 from brain surface) under isoflurane anesthesia, as described previously (39).…”

Section: Methodsmentioning

confidence: 99%

Off-manifold coding in visual cortex revealed by sleep

Oliveira

Kim

Qiu

et al. 2022

Preprint

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Low-dimensional dynamics and movement-related activity are found throughout the brain. However, primary visual cortex contains high-dimensional sensory representations, raising the question of how low-dimensional dynamics and high-dimensional representations coexist. Here we approached this question by analyzing neuronal activity during slow-wave sleep, which provided reliable estimates of low-dimensional, internally-generated manifold structure. We found that movements and visual scenes were both encoded in the on-manifold subspace, which accounts for more variance than chance during sleep, but visual scenes were also encoded in the off-manifold subspace, which accounts for less variance than chance during sleep. This off-manifold subspace contains sparse activity in the neurons with the strongest low-dimensional modulation by movement, which paradoxically prevents movement-evoked activity from interfering with high-dimensional stimulus representations. These results reveal an unexpected link between low-dimensional dynamics and sparse coding, suggesting that these phenomena play a role in creating and accessing an off-manifold coding space for high- dimensional representations.

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Hybrid offspring of C57BL/6J mice exhibit improved properties for neurobehavioral research

Cited by 3 publications

References 72 publications

Restoring functional D2- to D1-neuron correspondence enables goal-directed action control in long-lived striatal circuits

Restoring functional D2- to D1-neuron correspondence enables goal-directed action control in long-lived striatal circuits

Incubation of palatable food craving is associated with brain-wide neuronal activation in mice

Off-manifold coding in visual cortex revealed by sleep

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