Unraveling the mechanisms of deep-brain stimulation of the internal capsule in a mouse model DOI Creative Commons
Bastijn J.G. van den Boom, Alfredo Elhazaz-Fernandez,

Peter A. Rasmussen

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 4, 2023

Deep-brain stimulation (DBS) is an effective treatment for patients suffering from otherwise therapy-resistant psychiatric disorders, including obsessive-compulsive disorder. Modulation of cortico-striatal circuits has been suggested as a mechanism action. To gain mechanistic insight, we monitored neuronal activity in regions mouse model compulsive behavior, while systematically varying clinically-relevant parameters internal-capsule DBS. DBS showed dose-dependent effects on both brain and behavior: An increasing, yet balanced, number excited inhibited neurons was recruited, scattered throughout regions, excessive grooming decreased. Such recruitment did not alter basic function such resting-state activity, only occurred awake animals, indicating dependency network activity. In addition to these widespread effects, observed specific involvement the medial orbitofrontal cortex therapeutic outcomes, which corroborated by optogenetic stimulation. Together, our findings provide insight into how exerts its behaviors.

Language: Английский

Sleep/wake changes in perturbational complexity in rats and mice DOI Creative Commons
Matías Cavelli,

Rong Mao,

Graham Findlay

et al.

iScience, Journal Year: 2023, Volume and Issue: 26(3), P. 106186 - 106186

Published: Feb. 13, 2023

In humans, the level of consciousness is assessed by quantifying spatiotemporal complexity cortical responses using Perturbational Complexity Index (PCI) and related PCIst (st, state transitions). Here we validate in freely moving rats mice showing that it lower NREM sleep slow wave anesthesia than wake or REM sleep, as humans. We then show (1) low associated with occurrence an OFF period neuronal silence; (2) stimulation deep, but not superficial, layers leads to reliable changes across sleep/wake anesthesia; (3) consistent are independent which single area being stimulated recorded, except for recordings mouse prefrontal cortex. These experiments can reliably measure vigilance states unresponsive animals support hypothesis when disrupts causal interactions networks.

Language: Английский

Citations

19
Reorganization of adolescent prefrontal cortex circuitry is required for mouse cognitive maturation DOI Creative Commons
Jastyn A. Pöpplau,

Timo Schwarze,

Мария Дорофейкова

et al.

Neuron, Journal Year: 2023, Volume and Issue: 112(3), P. 421 - 440.e7

Published: Nov. 17, 2023

Most cognitive functions involving the prefrontal cortex emerge during late development. Increasing evidence links this delayed maturation to protracted timeline of development, which likely does not reach full maturity before end adolescence. However, underlying mechanisms that drive emergence and fine-tuning abilities adolescence, caused by circuit wiring, are still unknown. Here, we continuously monitored activity throughout postnatal development mice showed an initial increase was interrupted extensive microglia-mediated breakdown activity, followed rewiring elements achieve adult-like patterns synchrony. Interfering with these processes but adulthood, led a long-lasting microglia-induced disruption neuronal morphology decreased abilities. These results identified nonlinear reorganization circuits adolescence revealed its importance for adult network function processing.

Language: Английский

Citations

18
Dorsal peduncular cortex activity modulates affective behavior and fear extinction in mice DOI
Justin J. Botterill,

Abdessattar Khlaifia,

Ryan Appings

et al.

Neuropsychopharmacology, Journal Year: 2024, Volume and Issue: 49(6), P. 993 - 1006

Published: Jan. 17, 2024

Language: Английский

Citations

8
ACE2 Rescues Sepsis-Associated Encephalopathy by Reducing Inflammation, Oxidative Stress, and Neuronal Apoptosis via the Nrf2/Sestrin2 Signaling Pathway DOI
Ya Li,

Tiantian Wan,

Jiaxin Li

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: March 27, 2024

Language: Английский

Citations

7
Sex differences in the rodent medial prefrontal cortex – What Do and Don't we know? DOI
Mikaela A. Laine, Eliza M. Greiner, Rebecca M. Shansky

et al.

Neuropharmacology, Journal Year: 2024, Volume and Issue: 248, P. 109867 - 109867

Published: Feb. 20, 2024

Language: Английский

Citations

6
Behavioral and cortical arousal from sleep, muscimol-induced coma, and anesthesia by direct optogenetic stimulation of cortical neurons DOI Creative Commons

Rong Mao,

Matías Cavelli, Graham Findlay

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(6), P. 109919 - 109919

Published: May 7, 2024

Highlights•Optogenetic activation of cortical neurons wakes up mice from NREM and REM sleep•Awakenings are induced more effectively in posterior parietal than prefrontal cortex•Cortical opto stimulation causes EEG behavioral arousal coma•Cortical during deep sevo-dex anesthesiaSummaryThe cerebral cortex is widely considered part the neural substrate consciousness, but direct causal evidence missing. Here, we tested whether optogenetic (PtA) or medial (mPFC) sufficient for three states characterized by progressively deeper unresponsiveness: sleep, a coma-like state muscimol injection midbrain, sevoflurane-dexmedetomidine anesthesia. We find that always awakens both sleep with PtA requiring weaker/shorter light pulses mPFC. Moreover, most cases produce (decrease low frequencies) (recovery righting reflex) brainstem coma, as well These findings provide and/or anesthesia.Graphical abstract

Language: Английский

Citations

6
Population-level coding of avoidance learning in medial prefrontal cortex DOI Creative Commons
Benjamin Ehret, Roman Boehringer, Elizabeth A. Amadei

et al.

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(9), P. 1805 - 1815

Published: July 29, 2024

Abstract The medial prefrontal cortex (mPFC) has been proposed to link sensory inputs and behavioral outputs mediate the execution of learned behaviors. However, how such a is implemented remained unclear. To measure neural correlates stimuli behaviors, we performed population calcium imaging during new tone-signaled active avoidance paradigm in mice. We developed an analysis approach based on dimensionality reduction decoding that allowed us identify interpretable task-related activity patterns. While large fraction tone-evoked was not informative about behavior execution, identified pattern predictive tone-induced actions did occur for spontaneous with similar motion kinematics. Moreover, this avoidance-specific differed between distinct two consecutive tasks. Overall, our results are consistent model which mPFC contributes selection goal-directed by transforming into specific through distributed population-level computations.

Language: Английский

Citations

6
The Medial Prefrontal Cortex and Fear Memory: Dynamics, Connectivity, and Engrams DOI Open Access

Lucie Dixsaut,

Johannes Gräff

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(22), P. 12113 - 12113

Published: Nov. 9, 2021

It is becoming increasingly apparent that long-term memory formation relies on a distributed network of brain areas. While the hippocampus has been at center attention for decades, it now clear other regions, in particular medial prefrontal cortex (mPFC), are taking an active part as well. Recent evidence suggests mPFC-traditionally implicated storage memories-is already critical early phases such encoding. In this review, we summarize these findings, relate them to functional importance mPFC connectivity, and discuss role during consolidation with respect different theories storage. Owing its high connectivity areas subserving storage, emerges central hub across lifetime memory, although much still remains be discovered.

Language: Английский

Citations

33
Brain-wide reconstruction of inhibitory circuits after traumatic brain injury DOI Creative Commons

Jan C. Frankowski,

Alexa Tierno, Shreya Pavani

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: June 14, 2022

Abstract Despite the fundamental importance of understanding brain’s wiring diagram, our knowledge how neuronal connectivity is rewired by traumatic brain injury remains remarkably incomplete. Here we use cellular resolution whole-brain imaging to generate brain-wide maps input inhibitory neurons in a mouse model injury. We find that somatostatin interneurons are converted into hyperconnected hubs multiple regions, with rich local network connections but diminished long-range inputs, even at areas not directly damaged. The loss does correlate cell distant regions. Interneurons transplanted site receive orthotopic and input, suggesting machinery for establishing intact after severe Our results uncover potential strategy sustain optimize inhibition involves spatial reorganization direct inputs across brain.

Language: Английский

Citations

23
Distributed and specific encoding of sensory, motor, and decision information in the mouse neocortex during goal-directed behavior DOI Creative Commons

Anastasiia Oryshchuk,

Christos Sourmpis,

Julie Weverbergh

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 43(1), P. 113618 - 113618

Published: Dec. 26, 2023

Goal-directed behaviors involve coordinated activity in many cortical areas, but whether the encoding of task variables is distributed across areas or more specifically represented distinct remains unclear. Here, we compared representations sensory, motor, and decision information whisker primary somatosensory cortex, medial prefrontal tongue-jaw motor cortex mice trained to lick response a stimulus with that were not taught this association. Irrespective learning, properties sensory best encoded whereas fine movement kinematics cortex. However, initiation all three neurons being selective, showing minimal responses miss trials during spontaneous licks. Our results reconcile previous studies indicating highly specific vs. sensorimotor processing.

Language: Английский

Citations

14