14 research outputs found
Multiphoton fluorescence, second harmonic generation, and fluorescence lifetime imaging of whole cleared mouse organs
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In Vivo Interrogation of Spinal Mechanosensory Circuits
No full textSummarySpinal dorsal horn circuits receive, process, and transmit somatosensory information. To understand how specific components of these circuits contribute to behavior, it is critical to be able to directly modulate their activity in unanesthetized in vivo conditions. Here, we develop experimental tools that enable optogenetic control of spinal circuitry in freely moving mice using commonly available materials. We use these tools to examine mechanosensory processing in the spinal cord and observe that optogenetic activation of somatostatin-positive interneurons facilitates both mechanosensory and itch-related behavior, while reversible chemogenetic inhibition of these neurons suppresses mechanosensation. These results extend recent findings regarding the processing of mechanosensory information in the spinal cord and indicate the potential for activity-induced release of the somatostatin neuropeptide to affect processing of itch. The spinal implant approach we describe here is likely to enable a wide range of studies to elucidate spinal circuits underlying pain, touch, itch, and movement
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Plexus 2021: Emergence
No full textEditor's Note PLEXUS is a student-organized publication that showcases creative work by medical students, physicians, faculty, and others in the UCI medical community. Through the universal language of art, the journal aspires to connect those who seek to heal and to be healed. We hope that PLEXUS will always be a creative and welcoming space in which we can all reflect and share our experiences in medicine and in life.This year, more than ever, we hope that PLEXUS can provide solace to those who contribute to and view its pages. The unprecedented challenges of the last year have brought us incredible hardships and sorrow, but also inspired newfound strength and profound kindness. In this year’s 22nd edition of PLEXUS, we embrace and celebrate all of this as part of the process of Emergence.In this issue, we highlight the past year as a time of new things coming into being – whether good or bad – and to hold hope for the possibility of change for the better. Emergence is a process of coming to view and bringing things to light as well as the philosophy that greater things may arise which are unexpected and far better than any of the parts we see.We are incredibly grateful to our amazing community for their support in sustaining PLEXUS. This year we are lucky to have a wonderful team of MS1 associate editors led by Celina Yang: Riya Bansal, Aaron Frank, Kathleen Powers, and Kelsey Roman. We would like to give special thanks to our faculty advisors Dr. Johanna Shapiro, Dr. Tan Nguyen and Dr. Frank Meyskens. This journal would not have been possiblewithout their continuous support and guidance.We hope you enjoy PLEXUS 2021: Emergence.Editors in Chief: Ashley Hope, Kenneth Schmitt Congratulations to the winners of the 2021 medical student competition!Visual: Breaking Wave by Tammy Tran (MS3) Bloom/Plume/Bloom by Qingxing Liang (MS2)Written: Dragonfly in Amber by Bethlehem Tesfaye (MS1), A Little Soda for Thought by Anna Cardall (MS3)Performance: Emergence (Darkness) by Alex Richardson (MS3), On My Way remix by Harrison Lam (MS2)(front cover) Egg By: Sam Vesuna (MS3
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Deep posteromedial cortical rhythm in dissociation
No full textAdvanced imaging methods now allow cell-type-specific recording of neural activity across the mammalian brain, potentially enabling the exploration of how brain-wide dynamical patterns give rise to complex behavioural states1-12. Dissociation is an altered behavioural state in which the integrity of experience is disrupted, resulting in reproducible cognitive phenomena including the dissociation of stimulus detection from stimulus-related affective responses. Dissociation can occur as a result of trauma, epilepsy or dissociative drug use13,14, but despite its substantial basic and clinical importance, the underlying neurophysiology of this state is unknown. Here we establish such a dissociation-like state in mice, induced by precisely-dosed administration of ketamine or phencyclidine. Large-scale imaging of neural activity revealed that these dissociative agents elicited a 1-3-Hz rhythm in layer 5 neurons of the retrosplenial cortex. Electrophysiological recording with four simultaneously deployed high-density probes revealed rhythmic coupling of the retrosplenial cortex with anatomically connected components of thalamus circuitry, but uncoupling from most other brain regions was observed-including a notable inverse correlation with frontally projecting thalamic nuclei. In testing for causal significance, we found that rhythmic optogenetic activation of retrosplenial cortex layer 5 neurons recapitulated dissociation-like behavioural effects. Local retrosplenial hyperpolarization-activated cyclic-nucleotide-gated potassium channel 1 (HCN1) pacemakers were required for systemic ketamine to induce this rhythm and to elicit dissociation-like behavioural effects. In a patient with focal epilepsy, simultaneous intracranial stereoencephalography recordings from across the brain revealed a similarly localized rhythm in the homologous deep posteromedial cortex that was temporally correlated with pre-seizure self-reported dissociation, and local brief electrical stimulation of this region elicited dissociative experiences. These results identify the molecular, cellular and physiological properties of a conserved deep posteromedial cortical rhythm that underlies states of dissociation
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Cell-type-specific population dynamics of diverse reward computations.
No full textComputational analysis of cellular activity has developed largely independently of modern transcriptomic cell typology, but integrating these approaches may be essential for full insight into cellular-level mechanisms underlying brain function and dysfunction. Applying this approach to the habenula (a structure with diverse, intermingled molecular, anatomical, and computational features), we identified encoding of reward-predictive cues and reward outcomes in distinct genetically defined neural populations, including TH+ cells and Tac1+ cells. Data from genetically targeted recordings were used to train an optimized nonlinear dynamical systems model and revealed activity dynamics consistent with a line attractor. High-density, cell-type-specific electrophysiological recordings and optogenetic perturbation provided supporting evidence for this model. Reverse-engineering predicted how Tac1+ cells might integrate reward history, which was complemented by in vivo experimentation. This integrated approach describes a process by which data-driven computational models of population activity can generate and frame actionable hypotheses for cell-type-specific investigation in biological systems
