Investigating the role of Prefrontal Neurons in cognitive tasks through Fiber Photometry and Adapted Barnes Maze Protocols

The medial prefrontal cortex (mPFC) is essential in the execution of cognitive tasks, however very little is known on how these neurons are modulated during specific tasks and which subtype of neurons are responsible for so. Therego, with the intention of addressing this issue, we recorded mPFC gabaergic and glutamatergic activation patterns through fiber photometry (FIP) in mice, while simultaneously performing the Barnes Maze (BM) cognitive task (4 day behavioral trial). In addition, an altered structural and procedural protocol for BM was validated in this study due to necessary modifications allowing FIP and BM to happen simultaneously. A successful protocol validation was followed by our preliminary results, which showed that both glutamatergic and gabaergic neurons presented significant change in activation intensity and number of events in specific contexts throughout the task days. In addition, when stratified and crossed with BM performance parameters, such as latency to complete tasks and adopted strategy, glutamatergic and gabaergic neurons presented a significant decline in both activation patterns and number of activation events throughout the days. This data suggest not only an important role of glutamatergic and gabaergic mPFC neurons in learning, memory and decision making, but also that activation patterns of each of these groups may serve as markers for cognitive progression and/or dysfunction. KEY-WORDS: Memory, Learning, Decision Making, Medial Prefrontal Cortex (mPFC), Fiber Photometry (FIP), Barnes Maze (BM), Glutamatergic, Gabaergic, Neuronal Activity, Neuronal Activation Patterns, Neuronal Dynamics.

O córtex pré-frontal medial (mPFC) é essencial na execução de tarefas cognitivas, no entanto, pouco se sabe sobre como esses neurônios são modulados durante tarefas específicas e qual subtipo de neurônios é responsável por isso. Portanto, com a intenção de abordar essa questão, registramos os padrões de ativação de neurônios gabaérgicos e glutamatérgicos do mPFC por meio de fotometria de fibra (FIP) em camundongos, enquanto realizávamos simultaneamente a tarefa cognitiva do Labirinto de Barnes (BM) (ensaio comportamental de 4 dias). Além disso, um protocolo estrutural e procedimental alterado para o BM foi validado neste estudo devido a modificações necessárias que permitiram a realização simultânea de FIP e BM. Uma validação bem-sucedida do protocolo foi seguida pelos nossos resultados preliminares, que mostraram que tanto os neurônios glutamatérgicos quanto os gabaérgicos apresentaram mudanças significativas na intensidade de ativação e no número de eventos em contextos específicos ao longo dos dias da tarefa. Além disso, quando estratificados e cruzados com parâmetros de desempenho do BM, como latência para completar as tarefas e estratégia adotada, os neurônios glutamatérgicos e gabaérgicos apresentaram uma diminuição significativa nos padrões de ativação e no número de eventos de ativação ao longo dos dias. Esses dados sugerem não apenas um papel importante dos neurônios glutamatérgicos e gabaérgicos do mPFC na aprendizagem, memória e tomada de decisões, mas também que os padrões de ativação de cada um desses grupos podem servir como marcadores de progressão e/ou disfunção cognitiva. PALAVRAS-CHAVE: Memória, Aprendizagem, Tomada de Decisões, Córtex Pré-Frontal Medial (mPFC), Fotometria de Fibra (FIP), Labirinto de Barnes (BM), Glutamatérgico, Gabaérgico, Atividade Neuronal, Padrões de Ativação Neuronal, Dinâmica Neuronal.

The Dynamics of Dopamine D2 Receptor-Expressing Striatal Neurons and the Downstream Circuit Underlying L-Dopa-Induced Dyskinesia in Rats / 神经科学通报·英文版

L-dopa (l-3,4-dihydroxyphenylalanine)-induced dyskinesia (LID) is a debilitating complication of dopamine replacement therapy for Parkinson's disease. The potential contribution of striatal D2 receptor (D2R)-positive neurons and downstream circuits in the pathophysiology of LID remains unclear. In this study, we investigated the role of striatal D2R+ neurons and downstream globus pallidus externa (GPe) neurons in a rat model of LID. Intrastriatal administration of raclopride, a D2R antagonist, significantly inhibited dyskinetic behavior, while intrastriatal administration of pramipexole, a D2-like receptor agonist, yielded aggravation of dyskinesia in LID rats. Fiber photometry revealed the overinhibition of striatal D2R+ neurons and hyperactivity of downstream GPe neurons during the dyskinetic phase of LID rats. In contrast, the striatal D2R+ neurons showed intermittent synchronized overactivity in the decay phase of dyskinesia. Consistent with the above findings, optogenetic activation of striatal D2R+ neurons or their projections in the GPe was adequate to suppress most of the dyskinetic behaviors of LID rats. Our data demonstrate that the aberrant activity of striatal D2R+ neurons and downstream GPe neurons is a decisive mechanism mediating dyskinetic symptoms in LID rats.

Facilitation of behavioral and cortical emergence from isoflurane anesthesia by GABAergic neurons in basal forebrain / 中国药理学与毒理学杂志

OBJECTIVE To reveal the role of the basal forebrain(BF)GABAergic neurons in the regulation of isoflurane anesthesia and to elucidate the underlying neural pathways.METHODS The activity of BF GABAer-gic neurons was monitored during isoflurane anesthesia using a genetically encoded calcium indicator in Vgat-Cre mice of both sexes.The activity of BF GABAer-gic neurons was manipulated by chemogenetic and opto-genetic approaches.Sensitivity,induction time and emer-gence time of isoflurane anesthesia were estimated by righting reflex.The electroencephalogram(EEG)power and burst-suppression were monitored by EEG recording.The effects of activation of GABAergic BF-thalamic reticu-lar nucleus(TRN)pathway on isoflurane anesthesia were investigated with optogenetics.RESULTS The activity of BF GABAergic neurons was generally inhibited during isoflurane anesthesia,obviously decreased during the induction of anesthesia and gradually restored during the emergence from anesthesia.Activation of BF GABAergic neurons with chemogenetics and optogenetics promoted behavioral emergence from isoflurane anesthesia,with decreased sensitivity to isoflurane,delayed induction and accelerated emergence from isoflurane anesthesia.Optogenetic activation of BF GABAergic neurons prom-oted cortical activity during isoflurane anesthesia,with decreased EEG delta power and burst suppression ratio during 0.8%and 1.4%isoflurane anesthesia,respectively.Similar to the effects of activating BF GABAergic cell bod-ies,photostimulation of BF GABAergic terminals in the TRN also strongly promoted cortical activation and behav-ioral emergence from isoflurane anesthesia.CONCLU-SION The GABAergic neurons in the BF is a key neural substrate for general anesthesia regulation that facilitates behavioral and cortical emergence from general anesthe-sia via the BF-TRN pathway.

Entrainment of Astrocytic and Neuronal Ca2+ Population Dynamics During Information Processing of Working Memory in Mice / 神经科学通报·英文版

Astrocytes are increasingly recognized to play an active role in learning and memory, but whether neural inputs can trigger event-specific astrocytic Ca2+ dynamics in real time to participate in working memory remains unclear due to the difficulties in directly monitoring astrocytic Ca2+ dynamics in animals performing tasks. Here, using fiber photometry, we showed that population astrocytic Ca2+ dynamics in the hippocampus were gated by sensory inputs (centered at the turning point of the T-maze) and modified by the reward delivery during the encoding and retrieval phases. Notably, there was a strong inter-locked and antagonistic relationship between the astrocytic and neuronal Ca2+ dynamics with a 3-s phase difference. Furthermore, there was a robust synchronization of astrocytic Ca2+ at the population level among the hippocampus, medial prefrontal cortex, and striatum. The inter-locked, bidirectional communication between astrocytes and neurons at the population level may contribute to the modulation of information processing in working memory.

Association of Increased Amygdala Activity with Stress-Induced Anxiety but not Social Avoidance Behavior in Mice / 神经科学通报·英文版

Chronic stress leads to many psychiatric disorders, including social and anxiety disorders that are associated with over-activation of neurons in the basolateral amygdala (BLA). However, not all individuals develop psychiatric diseases, many showing considerable resilience against stress exposure. Whether BLA neuronal activity is involved in regulating an individual's vulnerability to stress remains elusive. In this study, using a mouse model of chronic social defeat stress (CSDS), we divided the mice into susceptible and resilient subgroups based on their social interaction behavior. Using in vivo fiber photometry and in vitro patch-clamp recording, we showed that CSDS persistently (after 20 days of recovery from stress) increased BLA neuronal activity in all the mice regardless of their susceptible or resilient nature, although impaired social interaction behavior was only observed in susceptible mice. Increased anxiety-like behavior, on the other hand, was evident in both groups. Notably, the CSDS-induced increase of BLA neuronal activity correlated well with the heightened anxiety-like but not the social avoidance behavior in mice. These findings provide new insight to our understanding of the role of neuronal activity in the amygdala in mediating stress-related psychiatric disorders.

An Infrared Touch System for Automatic Behavior Monitoring / 神经科学通报·英文版

Key requirements of successful animal behavior research in the laboratory are robustness, objectivity, and high throughput, which apply to both the recording and analysis of behavior. Many automatic methods of monitoring animal behavior meet these requirements. However, they usually depend on high-performing hardware and sophisticated software, which may be expensive. Here, we describe an automatic infrared behavior-monitor (AIBM) system based on an infrared touchscreen frame. Using this, animal positions can be recorded and used for further behavioral analysis by any PC supporting touch events. This system detects animal behavior in real time and gives closed-loop feedback using relatively low computing resources and simple algorithms. The AIBM system automatically records and analyzes multiple types of animal behavior in a highly efficient, unbiased, and low-cost manner.

Distinct Characteristics of Odor-evoked Calcium and Electrophysiological Signals in Mitral/Tufted Cells in the Mouse Olfactory Bulb / 神经科学通报·英文版

Fiber photometry is a recently-developed method that indirectly measures neural activity by monitoring Ca

Dopamine D1 receptor in ventrolateral periaqueductal gray modulates propofol anesthesia in rats / 医学研究生学报

ObjectiveVentrolateral periaqueductal gray (vlPAG) locates in ascending reticular activating system, which plays a key role in the sleep-wake circle. However, the role of vlPAG in general anesthesia has not been identified. To investigate the effect of the dopamine receptor in vlPAG neurons on propofol anesthesia, we used real-time in vivo fiber photometry, microinjection and EEG.MethodsTo observe the alteration of neuronal activity in the vlPAG throughout propofol anesthesia, 10 Sprague-Dawley rats were used for calcium fiber photometry recording. 50 vlPAG bilateral microinjection models were established and assigned into five groups randomly, including D1R agonist group, D1R antagonist group, D2R agonist group, D2R antagonist group, and control group (n=10). Under propofol anesthesia, 1 μL of D1R agonist, D1R antagonist, D2R agonist, D2R antagonist, and isotonic saline were microinjected into the vlPAG of animals in the corresponding groups, respectively. The induction time, recovery time and the changes in electroencephalogram (EEG) before and after microinjection were recorded and analyzed.ResultsThe neuronal activity in the vlPAG was significantly inhibited during the induction period and markedly recovered during the recovery period from propofol anesthesia (P<0.05). Subsequently, the microinjection of D1R agonist into the vlPAG notably prolonged the induction time and reduced the emergence time of propofol anesthesia with a decrease of δ-band ratio. While the microinjection of D1R antagonist accelerated the induction time and prolonged the emergence time of propofol anesthesia with an increase of δ-band ratio and a decrease in β-band ratio in cortical EEG (P<0.05). The induction and recovery time of D2R agonist /antagonist group did not differ with those of control group. As well, EEG before and after microinjection in D2R agonist /antagonist group did not different.ConclusionThese results indicate that vlPAG modulates the process of propofol anesthesia via D1R.