Application of Fiber Photometry in the Study of Neurological Disorders
| May 16, 2023
Human brain has about 90 billion neurons that are interconnected to each other through synapses to form a complex neural network, which enables a variety of complex functions. The brain can synthesize and release hundreds of neurotransmitters and neural signals are transmitted between neurons through neurotransmitters released by synapses.
Neurons in the brain project to multiple brain regions through complex pathways, generating abundant functions such as learning, cognition, addiction, emotion, control, motivation, reward, etc. The fiber photometry system can characterize the activity of population neurons by detecting the fluorescence changes of calcium ions and neurotransmitters. Owing to the execution easiness, fiber photometry experiments have been widely applied in neuroscience research.
This article will take the readers through some experimental application scenarios of fiber photometry to help the readers better understand its application in neurological disorders and share how fiber photometry can advance new discoveries.
2.1 Depression – the molecular circuit mechanism of opioid abstinence-induced depressive behavior
Depression is the most common kind of aversions induced by drug abstinence. Studies have found that k-opioid receptors (KORs) are involved in depression-like behavior induced by opioid abstinence, and this behavior is caused by dopamine (DA) release reduction in the nucleus accumbens (NAc). However, the molecular mechanism and neuronal circuit by which KORs regulate the aversion associated with opioid abstinence are still unclear.
In the model of morphine abstinence-induced depression mice, Zan et al. used fiber photometry, patch clamp, chemical genetics and immunohistochemistry and other methods to reveal that morphine abstinence activates KORs by increasing the expression of dynorphin, the KOR ligand in the amygdala, thereby activating p38 MAPK and promoting GLT1 expression. The expression increase of GLT1 reduces the glutamatergic input from amygdala to NAc, thereby leading to morphine abstinence-induced depression-like behavior.
In this study, Zan et al. adopted fiber photometryto detect the activity of BLA-NAc neuron projection in morphine abstinent mice, and found that the signals in tail suspension test decreased rapidly after morphine abstinence, indicating that morphine abstinence reduced excitatory synaptic transmission from amygdala to NAc.
2.2 Memory – hypothalamic circuit regulates hippocampal neurogenesis to promote memory retrieval and fight against anxiety-like behavior
Adult hippocampal neurogenesis is crucial in memory and emotion processing. Hippocampal newborn neurons are generated, mature and integrated into existing circuits in DG, and this process is dynamically regulated by neural circuit activity. However, the influence of hippocampal newborn neurons modified by neural circuits on animal behavioral memory remains unclear.
Li et al. focused on the different stages of ABN development modified by SuM-DG circuit. Resorting to fiber photometry, optogenetics, chemical genetics, patch clamp and lineage tracing, they revealed that SuM-DG circuit modified adult hippocampal newborn neurons to promote memory retrieval and fight against anxiety.
In this study, Li et al. used fiber photometry to detect the activity of SuM-DG neuronal projection and unveiled that in enriched environment (EE), the activity of SuM neurons in mice increased significantly. After SuM ablation, the EE-induced neural response and the ABN-mediated behavioral improvement were eliminated, indicating that ABN modified by SuM-DG circuit can regulate memory behavior.
2.3 Psychosis – mPFC-Notch1signaling mediates METH-inducedpsychosis via Hes1-dependent suppression of GABAB1receptor expression
Methamphetamine (METH) is a widely abused stimulant drug. High-dose or long-term use of METH can induce psychosis (MIP). Currently, little is known about its pathogenesis. Although the Notch1 signaling pathway has been proven to play a role in the pathogenesis of some psychiatric disorders, its role in MIP is still unclear.
In the METH mouse model, Ni et al. uncovered a previously unrecognized Notch1-Hess1-GABAB1 receptor-dependent mechanism involving the regulation of mPFC neuronal activity and behavioral phenotypes in MIP using fiber photometry, immunohistochemistry, WB, PCR, and behavioral methods, and proposed an important association between Notch1 signaling and MIP-related neuroplasticity.
In this study, in order to verify whether the activity of mPFC neurons in METH-induced movement deficits is related to Notch1 signaling, Ni et al. downregulated the NICD expression of mPFC neurons via shRNA and used fiber photometry to record calcium signals of mPFC neurons simultaneously. The results showed that calcium signal decreased significantly after acute METH administration on day 1, while on day 23, the calcium signal decreased significantly and returned to normal within a short time after administration. Meanwhile, the calcium signal decreased significantly compared with that before administration. However, when given normal saline, no significant changes were observed in the signals of different groups in the acute phase and expression phase, indicating that the downregulation of NICD in mPFC can attenuate the neuronal activity of sensitized mice.
2.4 Pain – novel mechanism of analgesia mediated by VPMntng1-S1B pathway
When a part of our body is hurt, we often instinctively rub or massage it to reduce the pain. This phenomenon is referred to as touch-mediated analgesia. For the mechanism of touch-mediated analgesia, the primary somatosensory cortex (S1) mainly processes vibro-tactile information, but the exact role of S1 in nociception is still debated. Relatively little is known about whether and how S1 processes facial nociception information.
Lu et al. established a behavioral model of touch-mediated analgesia. Using experimental techniques such as fiber photometry, chemo genetics, in vivo calcium imaging, immunohistochemistry, behavioral evaluation, etc., they observed that, for mice, tactile signals generated by whisking could significantly relieve facial nociception and blocking the thalamus-to-barrel cortex (S1B) circuit on which this tactile signal transmission depends leads to the disappearance of this analgesia. By analyzing the calcium signals of S1B neurons, the authors found that whisking altered nociceptive signal processing in S1B neurons and advanced the transition of the neural state induced by noxious stimuli towards non-nocifensive actions. This study shows that S1B integrates facial tactile and noxious signals to enable touch-mediated analgesia.
In this study, Lu et al. used fiber photometry technology to detect whether the tactile signal generated by whisking depends on the neurons expressing Ntng1 in the ventral posterior medial nucleus (VPM) of the thalamus (VPMNtng1). It was observed that VPMNtng1 neurons responded more strongly to innocuous blowing stimulus (air puff) than to noxious stimulus (thermal or mechanical stimulus) and this was consistent with the VPM’s role of transmitting touch signals, indicating that the tactile signal generated by whisking can indeed suppress facial nociception.
In all of these studies above, the researchers used RWD fiber photometry system that facilitated smooth implementation of the experiment. RWD fiber photometry system has assisted the scientific research work of over 100 universities at home and abroad, such as Peking University, Zhejiang University, Stanford University, University College London, etc., and has contributed to the publication of research results by various research groups in top academic journals such as Nature Neuroscience.
9 channels, 3 wavelengths of excitation light sources. Highly sensitive detectors provide stable signal acquisition with no frame drop. Over 20 kinds of marking provide flexible definition of experimental requirements Fluorescence recording and behavioral video recording integrated Professional recording and analysis features enable data processing with one click.
Zan Gui-Ying, Wang Yu-Jun, Li Xue-Ping et al. Amygdalar κ-opioid receptor-dependent upregulating glutamate transporter 1 mediates depressive-like behaviors of opioid abstinence.[J] .Cell Rep, 2021, 37: 109913.
Li Ya-Dong, Luo Yan-Jia, Chen Ze-Ka et al. Hypothalamic modulation of adult hippocampal neurogenesis in mice confers activity-dependent regulation of memory and anxiety-like behavior.[J] .Nat Neurosci, 2022, 25: 630-645.
Ni Tong, Zhu Li, Wang Shuai et al. Medial prefrontal cortex Notch1 signalling mediates methamphetamine-induced psychosis via Hes1-dependent suppression of GABA receptor expression.[J] .Mol Psychiatry, 2022, 27: 4009-4022.
Lu Jinghao, Chen Bin, Levy Manuel et al. Somatosensory cortical signature of facial nociception and vibrotactile touch-induced analgesia.[J] .Sci Adv, 2022, 8: eabn6530.