Longitudinal monitoring of prefrontal cortical ensemble dynamics reveals new insights into stress habituation

Patel, Sachin; Johnson, Keenan; Adank, Danielle N.

doi:10.1016/j.ynstr.2022.100481

Cited by 8 publications

(3 citation statements)

References 41 publications

(54 reference statements)

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“…Punishment itself increased lOFC and PL activity regardless of exposure history or whether punishment was action contingent. This finding corroborates very recent longitudinal experiments which reported stable PL response to footshock (though drift in individual cells was noted) and provide insight into the paucity of data characterizing lOFC response to footshock stressors (Kim et al, 2017;Patel et al, 2022;Turner et al, 2021). Our design also allowed us to directly compare this response in each region within subjects.…”

Section: Divergent Activity Between Frontal Cortex Subregions In Lear...supporting

confidence: 88%

Complementary roles of orbitofrontal and prelimbic cortices in adaptation of reward motivated actions to learned anxiety

Jacobs,

Bogachuk,

Moghaddam

2023

Preprint

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Background: Anxiety is a common symptom of several mental health disorders and adversely affects motivated behaviors. Anxiety can emerge from associating risk of future harm while engaged in goal-guided actions. Using a recently developed behavioral paradigm to model this aspect of anxiety, we investigated the role of two cortical subregions, the prelimbic medial frontal cortex (PL) and lateral orbitofrontal cortex (lOFC), which have been implicated in anxiety and outcome expectation, in flexible representation of actions associated with harm risk. Methods: A seek-take reward-guided instrumental task design was used to train animals to associate the seek action with a variable risk of punishment. After learning, animals underwent extinction training for this association. Fiber photometry was used to measure and compare neuronal activity in PL and lOFC during learning and extinction. Results: Animals increased action suppression in response to punishment contingencies. This increase dissipated after extinction training. These behavioral changes were associated with region specific changes in neuronal activity. PL neuronal activity preferentially adapted to threat of punishment whereas lOFC activity adapted to safe aspects of the task. Moreover, correlated activity between these regions was suppressed during actions associated with harm risk suggesting that these regions may guide behavior independently under anxiety. Conclusions: These findings suggest the PL and lOFC serve distinct but complementary roles in the representation of learned anxiety. This dissociation may provide a mechanism for how overlapping cortical systems are implicated in reward-guided action execution during anxiety.

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Section: Divergent Activity Between Frontal Cortex Subregions In Lear...supporting

confidence: 88%

Complementary roles of orbitofrontal and prelimbic cortices in adaptation of reward motivated actions to learned anxiety

Jacobs,

Bogachuk,

Moghaddam

2023

Preprint

View full text Add to dashboard Cite

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“…Time also erodes memory ensembles, such that there is greater reactivation of hippocampal ensembles in an identical context at 5 days compared to 30 days post-experience (Denny et al, 2014). Memories of experiences close in time are also more likely to share overlapping neuronal ensembles than experiences separated by a week or more (Cai et al, 2016), and longitudinal calcium recordings of cells within prefrontal cortex shows substantial representational drift of stress-sensitive ensembles across days (Patel et al, 2022), which is likely due to destabilization of the ensemble during repeated retrieval (Josselyn et al, 2015; Cho et al, 2021). Given this, the length of time between initial ELS and adult stress exposures, and the different contexts in which each stress was experienced would predict low reactivation of ELS-sensitive cells in the current study.…”

Section: Discussionmentioning

confidence: 99%

Reactivation of early-life stress-sensitive neuronal ensembles contributes to lifelong stress hypersensitivity

Balouek

Mclain

Minerva

et al. 2022

Preprint

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Early-life stress (ELS) is one of the strongest lifetime risk factors for depression, anxiety, suicide, and other psychiatric disorders, particularly after facing additional stressful events later in life. Human and animal studies demonstrate that ELS sensitizes individuals to subsequent stress. However, the neurobiological basis of such stress sensitization remains largely unexplored. We hypothesized that ELS-induced stress sensitization would be detectable at the level of neuronal ensembles, such that cells activated by ELS would be more reactive to adult stress. To test this, we leveraged transgenic mice to genetically tag, track, and manipulate experience-activated neurons. We found that in both male and female mice, ELS-activated neurons within the nucleus accumbens (NAc), and to a lesser-extent the medial prefrontal cortex, were preferentially reactivated by adult stress. To test whether reactivation of ELS-activated ensembles in the NAc contributes to stress hypersensitivity, we expressed hM4Dis receptor in control or ELS-activated neurons of pups and chemogenetically inhibited their activity during experience of adult stress. Inhibition of ELS-activated NAc neurons, but not control-tagged neurons, ameliorated social avoidance behavior following chronic social defeat stress in males. These data provide evidence that ELS-induced stress hypersensitivity is encoded at the level of corticolimbic neuronal ensembles.

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“…Adeno-associated virus (AAV) injections are widely used for expressing GCaMP in target brain regions 11,12 . Following an AAV injection, a second surgical step is required for implantation of an optical device, most commonly a gradient refractive index (GRIN) lens, for monitoring fluorescence deep in the brain 5,13,14 . This two-step procedure results in reduced experimental success rates due to an increased incidence of tissue damage and difficulties in targeting both the virus and the optical lens to the same site within the brain ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Viral vector eluting lenses for single-step targeted expression of genetically-encoded activity sensors for in vivo microendoscopic calcium imaging

Jons,

Cheng,

Dong

et al. 2023

Preprint

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Optical methods for studying the brain are powerful tools for understanding how neural activity underlies complex behavior. These methods typically rely on genetically encoded sensors and actuators to monitor and control neural activity. For microendoscopic calcium imaging, injection of a virus followed by implantation of a lens probe is required to express a calcium sensor and enable optical access to the target brain region. This two-step process poses several challenges, chief among them being the risks associated with mistargeting and/or misalignment between virus expression zone, lens probe and target brain region. Here, we engineer an adeno-associated virus (AAV)-eluting polymer coating for gradient refractive index (GRIN) lenses enabling expression of a genetically encoded calcium indicator (GCaMP) directly within the brain region of interest upon implantation of the lens. This approach requires only one surgical step and guarantees alignment between GCaMP expression and lens in the brain. Additionally, the slow viral release from these coatings increases the working time for surgical implantation, expanding the brain regions and species amenable to this approach. These enhanced capabilities should accelerate neuroscience research utilizing optical methods and advance our understanding of the neural circuit mechanisms underlying brain function and behavior in health and disease.

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Longitudinal monitoring of prefrontal cortical ensemble dynamics reveals new insights into stress habituation

Cited by 8 publications

References 41 publications

Complementary roles of orbitofrontal and prelimbic cortices in adaptation of reward motivated actions to learned anxiety

Complementary roles of orbitofrontal and prelimbic cortices in adaptation of reward motivated actions to learned anxiety

Reactivation of early-life stress-sensitive neuronal ensembles contributes to lifelong stress hypersensitivity

Viral vector eluting lenses for single-step targeted expression of genetically-encoded activity sensors for in vivo microendoscopic calcium imaging

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