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Biology subjects

Hjort, M.

Publications and source records attributed to Hjort, M..

3 recordsLinked to original sources

Lithography-free Water Stable Conductive Polymer Nanowires

Free-standing nanowires can gain intracellular access without causing cellular stress or apoptosis. Current approaches to generate nanowires focus on lithographic patterning and inorganic materials (Si, GaAs, Al2O3, etc.) while organic materials are less explored. Use of organic conductive polymers allows for creation of soft mixed ion-electron conducting nanowires. Processing conductive polymers into nanowires is challenging due to the harsh chemicals and processing conditions used. Here, we demonstrate a lithography-free and scalable method to generate all-organic water-stable nanowires composed of conductive polymers. A nanoporous membrane is filled with conductive polymer in solution followed by a cross-linking step to make the polymer water stable. The surface of the membrane is anisotropically etched using a reactive ion etcher to reveal the polymer inside the pores, which extend from the membrane as nanowires. We interface the nanowires with model algal cells and human primary hematopoietic stem and progenitor cells. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/631660v1_ufig1.gif" ALT="Figure 1"> View larger version (56K): org.highwire.dtl.DTLVardef@bf44b3org.highwire.dtl.DTLVardef@13782baorg.highwire.dtl.DTLVardef@1679366org.highwire.dtl.DTLVardef@fe1677_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

Endogenous opioid dynamics in the dorsal striatum sculpt neural activity to control goal-directed action

Endogenous neuropeptides are uniquely poised to regulate neuronal activity and behavior across multiple timescales. Traditional studies ascribing neuropeptide contributions to behavior lack spatiotemporal precision. The endogenous opioid dynorphin is highly enriched in the dorsal striatum, known to be critical for regulating goal-directed behavior. However, the locus, the precise timescale, or functional role of endogenous dyn-KOR signaling on goal-directed behavior is unknown. Here, we report that local, time-locked dynorphin release from the dorsomedial striatum is necessary and sufficient for goal-directed behavior using a suite of high resolution modern approaches including in vivo two-photon imaging, neuropeptide biosensor detection, conditional deletions and time-locked optogenetic manipulations. We discovered that glutamatergic axon terminals from the basolateral amygdala evoke striatal dynorphin release, resulting in retrograde presynaptic GPCR inhibition during behavior. Collectively, our findings isolate a causal role for endogenous neuropeptide release at rapid timescales, and subsequent GPCR activity for tuning and promoting fundamental goal-directed behaviors.

neuroscience↗

Opioid-driven disruption of the septal complex reveals a role for neurotensin- expressing neurons in withdrawal

Because opioid withdrawal is an intensely aversive experience, persons with opioid use disorder (OUD) often relapse to avoid it. The lateral septum (LS) is a forebrain structure that is important in aversion processing, and previous studies have linked the lateral septum (LS) to substance use disorders. It is unclear, however, which precise LS cell types might contribute to the maladaptive state of withdrawal. To address this, we used single-nucleus RNA-sequencing to interrogate cell type specific gene expression changes induced by chronic morphine and withdrawal. We discovered that morphine globally disrupted the transcriptional profile of LS cell types, but Neurotensin-expressing neurons (Nts; LS-Nts neurons) were selectively activated by naloxone. Using two-photon calcium imaging and ex vivo electrophysiology, we next demonstrate that LS-Nts neurons receive enhanced glutamatergic drive in morphine-dependent mice and remain hyperactivated during opioid withdrawal. Finally, we showed that activating and silencing LS-Nts neurons during opioid withdrawal regulates pain coping behaviors and sociability. Together, these results suggest that LS-Nts neurons are a key neural substrate involved in opioid withdrawal and establish the LS as a crucial regulator of adaptive behaviors, specifically pertaining to OUD.

neuroscience↗