Biology subjects

Sonneborn, A.

Publications and source records attributed to Sonneborn, A..

5 recordsLinked to original sources

bioRxiv2026

A claustro-cortical loop times state transitions for flexible behavior

Metastable dynamics, in which neural activity moves between transiently stable patterns, have been proposed to underlie the real-time coordination on which the brains cognitive and behavioral functions depend1-3. In the cortex, the simplest form of this regime is the alternation between active UP states, in which neurons fire, and silent DOWN states, in which firing is strongly reduced, a bistable architecture that shapes how afferent information is processed 4-8. Such metastable dynamics are ubiquitous across cortex 9,10, yet how their state transitions are timed and controlled, and how this timing shapes behavior, remain open questions. Here we show, in freely behaving mice performing a cue-guided switching task, that the metastable dynamics of frontal cortex are jointly shaped by its reciprocal loop with the claustrum, a small and widely connected subcortical structure, and that the loops timing of these state transitions is required for efficient flexible behavior. Claustrum activity led the cortical UP-to-DOWN state transition, delivering to anterior cingulate cortex a low-dimensional drive aligned with the axis along which the cortical state switches. This drive was carried not by a rise in claustral firing but by transient coordination: population synchrony peaked at the transition even as mean rate fell. Silencing ACC-projecting claustrum terminals reduced directed claustro-cortical coupling, biased cortex away from the DOWN state by prolonging UP states and shortening DOWN states, and selectively impaired cue-driven switching while sparing exploratory foraging. These results place flexible behavior under the control of a defined cortico-subcortical loop that times cortical state transitions, offering a circuit-level entry point into the cognitive rigidity of many psychiatric and neurological conditions11-13.

neuroscience↗

bioRxiv2025

Combining the alpha-2 adrenergic agonist clonidine with naloxone rescues fentanyl-induced physiologic dysfunction and increases survival

Fentanyl leads to tens of thousands of overdose deaths every year despite widespread availability of naloxone. Like other opioids, fentanyl causes respiratory depression. Unlike morphine, high dose fentanyl rapidly produces airway obstruction, muscle rigidity, and cardiovascular failure. Using a rat model of opioid overdose, we compared the physiological effects of fentanyl and morphine and studied the efficacy of a novel rescue strategy. In contrast to morphine, we report that fentanyl more frequently causes respiratory failure secondary to vocal cord closure and leads to more severe cardiovascular disruption, including the blockade of baroreflex-like rebound in blood pressure. We also show that administration of intramuscular naloxone immediately after intravenous infusion of fentanyl did not improve survival. However, combining intramuscular naloxone with the alpha-2 adrenergic agonist clonidine rescued vocal cord function and stabilized cardiovascular and respiratory physiology from fentanyl-induced effects. Our findings demonstrate that fentanyl is associated with a unique and more severe toxidrome compared to morphine. Also, supplementing naloxone with drugs targeting the adrenergic system improves survival primarily by reopening the upper airway, implicating airway obstruction as a significant component of fentanyl-induced respiratory depression. Therefore, reversal of vocal cord closure appears to be the necessary precursor to the restoration of not only respiration, but also vascular autoregulation, a significant determinant of survival from fentanyl overdose.

pharmacology and toxicology↗

bioRxiv2024

Comparative analysis of spike-sorters in large-scale brainstem recordings

Recent technological advancements in high-density multi-channel electrodes have made it possible to record large numbers of neurons from previously inaccessible regions. While the performance of automated spike-sorters has been assessed in recordings from cortex, dentate gyrus, and thalamus, the most effective and efficient approach for spike-sorting can depend on the target region due to differing morphological and physiological characteristics. We therefore assessed the performance of five commonly used sorting packages, Kilosort3, MountainSort5, Tridesclous, SpyKING CIRCUS, and IronClust, in recordings from the rostral ventromedial medulla, a region that has been characterized using single-electrode recordings but that is essentially unexplored at the high-density network level. As demonstrated in other brain regions, each sorter produced unique results. Manual curation preferentially eliminated units detected by only one sorter. Kilosort3 and IronClust required the least curation while maintaining the largest number of units, whereas SpyKING CIRCUS and MountainSort5 required substantial curation. Tridesclous consistently identified the smallest number of units. Nonetheless, all sorters successfully identified classically defined RVM physiological cell types. These findings suggest that while the level of manual curation needed may vary across sorters, each can extract meaningful data from this deep brainstem site. Significance StatementHigh-density multichannel recording probes that can access deep brainstem structures have only recently become commercially available, but the performance of open-source spike-sorting packages applied to recordings from these regions has not yet been evaluated. The present findings demonstrate that Kilosort3, MountainSort5, Tridesclous, SpyKING CIRCUS, and IronClust can all be reasonably used to identify units in a deep brainstem structure, the rostral ventromedial medulla (RVM). However, manual curation of the output was essential for all sorters. Importantly, all sorters identified the known, physiologically defined RVM cell classes, confirming their utility for deep brainstem recordings. Our findings provide suggestions for processing parameters to use for brainstem recordings and highlight considerations when using high-density silicon probes in the brainstem.

neuroscience↗

bioRxiv2024

Divergent Subregional Information Processing in Mouse Prefrontal Cortex During Working Memory

Working memory (WM) is a critical cognitive function allowing recent information to be temporarily held in mind to inform future action. This process depends on coordination between key subregions in prefrontal cortex (PFC) and other connected brain areas. However, few studies have examined the degree of functional specialization between these subregions throughout the phases of WM using electrophysiological recordings in freely-moving animals, particularly mice. To this end, we recorded single-units in three neighboring medial PFC (mPFC) subregions in mouse - supplementary motor area (MOs), dorsomedial PFC (dmPFC), and ventromedial (vmPFC) - during a freely-behaving non-match-to-position WM task. We found divergent patterns of task-related activity across the phases of WM. The MOs is most active around task phase transitions and encodes the starting sample location most selectively. Dorsomedial PFC contains a more stable population code, including persistent sample-location-specific firing during a five second delay period. Finally, the vmPFC responds most strongly to reward-related information during the choice phase. Our results reveal anatomically and temporally segregated computation of WM task information in mPFC and motivate more precise consideration of the dynamic neural activity required for WM.

neuroscience↗

bioRxiv2023

The classic psychedelic DOI induces a persistent desynchronized state in medial prefrontal cortex

Administration or consumption of classic psychedelics (CPs) leads to profound changes in experience which are often described as highly novel and meaningful. They have shown substantial promise in treating depressive symptoms and may be therapeutic in other situations. Although research suggests that the therapeutic response is correlated with the intensity of the experience, the neural circuit basis for the alterations in experience caused by CPs requires further study. The medial prefrontal cortex (mPFC), where CPs have been shown to induce rapid, 5-HT2A receptor-dependent structural and neurophysiological changes, is believed to be a key site of action. To investigate the acute neural circuit changes induced by CPs, we recorded single neurons and local field potentials in the mPFC of freely behaving mice after administration of the 5-HT2A/2C receptor-selective CP, 2,5-Dimethoxy-4-iodoamphetamine (DOI). We segregated recordings into active and rest periods in order to examine cortical activity during desynchronized (active) and synchronized (rest) states. We found that DOI induced a robust decrease in low frequency power and decoupled rhythmic activity from neural population dynamics when animals were at rest, attenuating the usual synchronization that occurs during less active behavioral states. DOI also increased broadband gamma power and suppressed activity in fast-spiking neurons in both active and rest periods. Together, these results show that the CP DOI induces persistent desynchronization in mPFC, including during rest when mPFC typically exhibits more synchronized activity. This shift in cortical dynamics may in part underlie the longer-lasting effects of CPs on plasticity, and may be critical to their therapeutic properties.

neuroscience↗