Biology subjects

Bartley, A. F.

Publications and source records attributed to Bartley, A. F..

5 recordsLinked to original sources

bioRxiv2026

NPY+ Interneurons in Basolateral Amygdala are Activated by Aversive Stimuli

Traumatic events increase the risk for anxiety disorders, yet knowledge of how trauma modulates neuronal activity to induce anxiety is incomplete. The amygdala, which processes stressful sensory information, is enriched with interneurons that release the anxiolytic neurotransmitter neuropeptide Y (NPY). Amygdala NPY levels are reduced one week after an aversive event, suggesting chronic alteration of NPY+ interneurons; however, studies of in vivo amygdalar NPY+ cell activity during stressors are lacking. Here, we use a genetically encoded calcium sensor together with fiber photometry to investigate in vivo activation of NPY+ cells in basolateral amygdala (BLA) to aversive stimuli in mice. NPY+ cell activation was evaluated in response to two aversive stimuli, air puffs to the face (mild) and footshocks (strong). Air puffs caused a transient elevation of calcium in BLA NPY+ cells, indicating robust neuronal activation, in both male and female mice with no sex-dependent differences. Interestingly, there was habituation of the calcium signal in NPY+ cells to later air puff iterations. Strong footshocks also caused calcium elevation in both male and female mice with no sex-dependent differences. Excitingly, footshock induces a larger calcium response compared to air-puff. In contrast to air puff, the calcium signal to footshock was prolonged in later iterations. BLA NPY+ cell calcium signals were consistent in response to the same footshock protocol delivered 1 week later, indicating that activation of NPY+ cells by footshock is stable across this timeframe. Taken together, these results reveal a potential role for NPY+ interneurons in basolateral amygdala during aversive events.

neuroscience↗

bioRxiv2024

Modulation of Temporoammonic-CA1 Synapses by Neuropeptide Y is Through Y1 Receptors

The reduction of neuropeptide Y (NPY), an abundant neuromodulator in the brain, has been implicated in multiple neuropsychiatric disorders, such as depression and post-traumatic stress disorder (PTSD). The CA1 region of hippocampus is an important area for anxiety and highly expresses NPY. Injection of NPY into the CA1 is anxiolytic and has been shown to alleviate behavioral symptoms in a model of traumatic stress. It is known that activation of NPY Y1 receptors has anxiolytic effects and that NPYs anxiolytic effects in CA1 are blocked by an NPY Y1 receptor antagonist. However, the location of Y1 receptors mediating NPYs anxiolytic effects in CA1 is not yet known. CA1 receives inputs from entorhinal cortex through the temporammonic pathway (TA), which has been shown to be important for fear learning and sensitive to stress. Our lab previously showed that NPY reduces TA-evoked synaptic responses, however, the subtype of NPY receptor mediating this effect is not yet known. In this study, we show that Y1 receptors mediate the effects of both exogenous (bath-applied) and endogenously-released NPY in the TA pathway. This is the first demonstration of a Y1 receptor-mediated effect on synaptic function in CA1. Interestingly, chronic cell-type specific overexpression of NPY impairs the sensitivity of the TA pathway to NPY and the Y1 receptor agonist. However, the effect of NPY in the Schaffer collateral (SC) pathway, which is mediate by NPY Y2 receptors, is unaffected by NPY overexpression. There are pathway-specific differences in NPY receptors that modulate NPYs effects in CA1 and respond differently to NPY overexpression. Our results demonstrating that NPY acts at Y1 receptors in the TA pathway are consistent with the idea that the TA pathway underlies the anxiolytic effects of NPY in CA1.

neuroscience↗

bioRxiv2020

X-ray mediated scintillation increases synaptic activity via Cerium-doped LSO and Channelrhodopsin-2

Optogenetics is a widely used tool for studying neural circuits. However, non-invasive methods for light delivery in the brain are needed to avoid physical damage typically caused by intracranial insertion of light guides. An innovative strategy could employ X-ray activation of radioluminescent particles (RLPs) to emit localized light. We previously reported that RLPs composed of cerium doped lutetium oxyorthosilicate (LSO:Ce), an inorganic scintillator that emits blue light, are biocompatible with neuronal function and synaptic transmission. However, little is known about the consequences of acute X-ray exposure on synaptic function and long-term plasticity. Furthermore, modulation of neuronal or synaptic function by X-ray induced radioluminescence from RLPs has not yet been demonstrated. Here we show that 30 minutes of X-ray exposure at a rate of 0.042 Gy/second caused no change in the strength of basal glutamatergic transmission during extracellular dendritic field recordings in mouse hippocampal slices. Additionally, long-term potentiation (LTP), a robust measure of synaptic integrity, was able to be induced after X-ray exposure and expressed at a magnitude not different from control conditions (absence of X-rays). This is important as synaptic plasticity is critical to learning and memory. Next, we used molecular and electrophysiological approaches to determine if X-ray dependent radioluminescence emitted from RLPs can activate light sensitive proteins. We found that X-ray stimulation of RLPs elevated cAMP levels in HEK293T cells expressing OptoXR, a chimeric opsin receptor that combines the extracellular light-sensitive domain of channelrhodopsin-2 (ChR2) with an intracellular second messenger signaling cascade. This demonstrates that X-ray radioluminescence from LSO:Ce particles can activate OptoXR. Next, we tested whether X-ray activation of the RLPs can enhance synaptic activity in whole-cell recordings from hippocampal neurons expressing ChR2, both in cell culture and acute hippocampal slices. Importantly, X-ray radioluminescence caused an increase in the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in both systems, indicating activation of ChR2 and excitation of neurons. Together, our results show that X-ray activation of LSO:Ce particles can heighten cellular and synaptic function. The combination of LSO:Ce inorganic scintillators and X-rays is therefore a viable method for optogenetics as an alternative to more invasive light delivery methods.

neuroscience↗

bioRxiv2019

Localized delivery and uncaging of glutamate from MRI-visible albumin nanoclusters in the rat hippocampus using focused ultrasound

There is an ongoing need for noninvasive tools to manipulate brain activity with molecular, spatial and temporal specificity. Here we have investigated the use of MRI-visible, albumin-based nanoclusters for noninvasive, localized and temporally specific drug delivery to the rat brain. We demonstrated that IV injected nanoclusters could be deposited into target brain regions via focused ultrasound facilitated blood brain barrier opening. We showed that nanocluster location could be confirmed in vivo with MRI. Additionally, following confirmation of nanocluster delivery, release of the nanocluster payload into brain tissue can be triggered by a second focused ultrasound treatment performed without circulating microbubbles. Release of glutamate from nanoclusters in vivo caused enhanced c-Fos expression, indicating that the loading capacity of the nanoclusters is sufficient to induce neuronal activation. This novel technique for noninvasive stereotactic drug delivery to the brain with temporal specificity could provide a new way to study brain circuits in vivo preclinically with high relevance for clinical translation. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=36 SRC="FIGDIR/small/696237v4_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@b528f9org.highwire.dtl.DTLVardef@1950228org.highwire.dtl.DTLVardef@1c0ada0org.highwire.dtl.DTLVardef@c71790_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2019

LSO:Ce Inorganic Scintillators are Biocompatible with Neuronal and Circuit Function

Optogenetics is widely used in neuroscience to control neural circuits. However, non-invasive methods for light delivery in brain are needed to avoid physical damage caused by current methods. One potential strategy could employ x-ray activation of radioluminescent particles (RPLs), enabling localized light generation within the brain. RPLs composed of inorganic scintillators can emit light at various wavelengths depending upon composition. Cerium doped lutetium oxyorthosilicate (LSO:Ce), an inorganic scintillator that emits blue light in response to x-ray or UV stimulation, could potentially be used to control neural circuits through activation of channelrhodopsin-2 (ChR2), a light-gated cation channel. Whether inorganic scintillators themselves negatively impact neuronal processes and synaptic function is unknown, and was investigated here using cellular, molecular, and electrophysiological approaches. As proof of principle, we applied UV stimulation to 4 m LSO:Ce particles during whole-cell recording of CA1 pyramidal cells in acutely prepared hippocampal slices from mice that expressed ChR2 in glutamatergic neurons. We observed an increase in frequency and amplitude of spontaneous excitatory postsynaptic currents (EPSCs), indicating UV activation of ChR2 and excitation of neurons. Importantly, we found that LSO:Ce particles have no effect on survival of primary mouse cortical neurons, even after 24 hours of exposure. In extracellular dendritic field potential recordings, we observed no change in strength of basal glutamatergic transmission up to 3 hours of exposure to LSO:Ce microparticles. However, there was a slight decrease in the frequency of spontaneous EPSCs in whole-cell voltage-clamp recordings from CA1 pyramidal cells, with no change in current amplitudes. No changes in the amplitude or frequency of spontaneous inhibitory postsynaptic currents (IPSCs) were observed. Finally, long term potentiation (LTP), a synaptic modification believed to underlie learning and memory and a robust measure of synaptic integrity, was successfully induced, although the magnitude was slightly reduced. Together, these results show LSO:Ce particles are biocompatible even though there are modest effects on baseline synaptic function and long-term synaptic plasticity. Importantly, we show that light emitted from LSO:Ce particles is able to activate ChR2 and modify synaptic function. Therefore, LSO:Ce inorganic scintillators are potentially viable for use as a new light delivery system for optogenetics.

neuroscience↗