Trends in neuroanatomical research / 解剖学报

The basic structure of the nervous system is neurons and the connections formed by nerve fibers. Identifying different types of neurons in different parts of the nervous system, revealing the efferent and afferent nerve fibers they constitute, and elucidating the neuroactive substances and receptors involved, provide the basis for the regulation of neuronal activity and the uncovering of how the nervous system works. It is also the goal of neuroanatomy research. The rapid development of modern science and technology and interdisciplinary penetration require us to conduct in-depth neuroanatomy studies on specific neural pathways composed of specific types of neurons using specific neuroactive substances for specific neural functions. This also provides a good opportunity for us to clarify the structure of nervous system and analyze its working principle from macroscopic, mesoscopic and microscopic levels.

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.

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.

Interstitial ions regulate sleep and wakefulness / 中国临床药理学与治疗学

Electroencephalogram (EEG) is the super-imposed electrical signals at the scalp electrodes generated from neuronal activity. The combined signals of EEG and electromyogram (EMG) can be used to identify sleep and wake states. Therefore, factors affecting the neuronal activity could possibly modulate the state of sleep and wake. It has been well-defined in the past decades that postsynaptic neuronal activity is mediated by neurotransmitters release from presynaptic neurons. Neural circuits have been proposed to be the structural basis and functional system that regulate sleep-wake. Beside presynaptic inputs, neuronal activity can also be mediated by extracellular environment. All cellular elements of the central nervous system (CNS) are consistently exposed to the interstitial milieu. The interstitial ion compositions can affect action potential firings, neurotransmitter release, and synaptic transmission. The super-imposed single neuronal electrical activity will eventually integrate the whole brain state shift. Frontier studies suggest that the interstitial ion compositions could mirror or drive state transitions, such as, sleep, wakefulness and locomotion. Here we provide an literature review of the roles of interstitial ions in regulating neuronal activity, as well as sleep and wake state maintenances and transitions.

Effect of Electroacupuncture at "Shenmen" (HT 7)- "Tongli" (HT 5) of Heart Meridian on Neuronal Activities in Paraventricular Nucleus of Hypothalamus in Myocardial Ischemia Rats / 针刺研究

OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of "Shenmen" (HT 7) - "Tongli" (HT 5) segment of the Heart Meridian on neuronal electrical activities of hypothalamic paraventricular nucleus (PVN) in rats with myocardial ischemia (MI), so as to investigate its possible mechanism underlying improvement of MI. METHODS: Thirty-two SD rats were randomly divided into sham control, model, HT 7-HT 5 and "Taiyuan" (LU 9)- "Lieque" (LU 7) groups (n=8 in each group). EA preconditioning (2 Hz, 1 V, 20 min) was applied to bilateral HT 7-HT 5 and bilateral LU 9-LU 7, respectively, once everyday for 7 days. The electrical activities of the right PVN region were recorded by the implanted microelectrode array(2×4)and Plexon multi-channel acquisition system. Cluster analysis of neuronal signals was carried out by Offline Sorter software. The discharge waveforms, autocorrelation and cross-correlation of neuronal activities were analyzed by using Neuro Explorer software. RESULTS: Cluster analysis of neuronal signals showed that 2, 2, 1 and 1 interneuron in the sham, model, HT 7-HT 5, and LU 9-LU 7 groups, and 3 pyramidal neurons in the HT 7-HT 5 were acquired. Cross correlation analysis showed that the SPK 02 a and SPK 02 b neurons of the HT 7-HT 5 group had an inhibitory relationship. The total discharge frequency was significantly increased in the model group relevant to the sham group (P<0.01), and was markedly lower in the HT 7-HT 5 group than in the model group and LU 9-LU 7 group (P<0.01). Real-time spectrum analysis showed that the local field potential spectrum energy of the HT 7-HT 5 group was significantly lower than that of the model group and the LU 9-LU 7 group. CONCLUSION: EA of HT 7-HT 5 segment of the Heart Meridian can inhibit the electrical activity of interneuron and activate the electrical activity of pyramidal neuron in PVN region, and an inhibitory relationship exists between the interneuron and pyramidal neuron in MI rats, which may be a mechanism of EA in regulating activities of the ischemic heart.

Altered Neuronal Activity in the Central Nucleus of the Amygdala Induced by Restraint Water-Immersion Stress in Rats / 神经科学通报·英文版

Restraint water-immersion stress (RWIS), a compound stress model, has been widely used to induce acute gastric ulceration in rats. A wealth of evidence suggests that the central nucleus of the amygdala (CEA) is a focal region for mediating the biological response to stress. Different stressors induce distinct alterations of neuronal activity in the CEA; however, few studies have reported the characteristics of CEA neuronal activity induced by RWIS. Therefore, we explored this issue using immunohistochemistry and in vivo extracellular single-unit recording. Our results showed that RWIS and restraint stress (RS) differentially changed the c-Fos expression and firing properties of neurons in the medial CEA. In addition, RWIS, but not RS, induced the activation of corticotropin-releasing hormone neurons in the CEA. These findings suggested that specific neuronal activation in the CEA is involved in the formation of RWIS-induced gastric ulcers. This study also provides a possible theoretical explanation for the different gastric dysfunctions induced by different stressors.

The Centrifugal Influence on Gustatory Neurons in the Nucleus of the Solitary Tract

Neuronal activities of taste-responsive cells in the nucleus of the solitary tract (NST) are affected by various physiological factors, such as blood glucose level or sodium imbalance. These phenomena suggest that NST taste neurons are under the influence of neural substrates that regulate nutritional homeostasis. In this study, we reviewed a series of in vivo electrophysiological investigations that demonstrate that forebrain nuclei, such as the lateral hypothalamus or central nucleus of the amygdala, send descending projections and modulate neuronal activity of gustatory neurons in the NST. These centrifugal modulations may mediate plasticity of taste response in the NST under different physiological conditions.

Electrical stimulation can facilitate vestibular compensation following unilateral labyrinthectomy in rats

To investigate the effects of electrical stimulation on vestibular compensation, which is the recovery of vestibular symptoms following unilateral labyrinthectomy (UL), intermittent electrical stimulation was applied to the injured vestibular portion in Sprague-Dawley rats. Vestibuloocular and vestibulospinal reflexes, electrical activity and expression of c-Fos protein in medial vestibular nuclei (MVN) were measured with time following UL. Spontaneous nystagmus occurred with frequency of 2.9+/-0.2 beats/sec at 2 hours after UL and disappeared after 72 hours. Electrical stimulation decreased the frequency of nystagmus significantly till 24 hours after UL. Roll head deviation was 107+/-9.7degree at 2 hours after UL and the deviation was maintained till 72 hours, but electrical stimulation decreased the deviation significantly 6 hours after UL. Resting activity of type I neurons in ipsilateral MVN to the injured vestibular side decreased significantly compared with control at 6 and 24 hours after UL, but the activity of type I neurons was recovered to control level by electrical stimulation at 24 hours after UL. Gain of type I neurons induced by sinusoidal rotation of 0.1 Hz decreased significantly till 24 hours after UL, but electrical stimulation restored the activity at 24 hours. The gain of type II neurons decreased significantly at 6 hours after UL, but electrical stimulation restored the activity. Expression of c-Fos protein was asymmetric between bilateral MVN till 24 hours after UL, but the asymmetry disappeared by electrical stimulation 6 hours after UL. These results suggest that electrical stimulation to the injured vestibular portion facilitates vestibular compensation following UL by restoration of symmetry of neuronal activity between bilateral vestibular nuclei resulting from increased activity in ipsilateral vestibular nuclei to the injured side.

Effects of GABA on pancreatic exocrine secretion of rats

Since GABA and its related enzymes had been determined in beta-cells of pancreas islets, effects of GABA on pancreatic exocrine secretion were investigated in the isolated perfused rat pancreas. GABA, given intra-arterially at concentrations of 3, 10, 30 and 100 microM, did not exert any influence on spontaneous or secretin (12 pM)-induced pancreatic exocrine secretion. However, GABA further elevated cholecystokinin (10 pM)-, gastrin-releasing peptide (100 pM)- or electrical field stimulation-induced pancreatic secretions of fluid and amylase, dose-dependently. The GABA-enhanced CCK-induced pancreatic secretions were completely blocked by bicuculline (10 microM), a GABAA receptor antagonist but not affected by saclofen (10 microM), a GABA(B) receptor antagonist. The enhancing effects of GABA (30 microM) on CCK-induced pancreatic secretions were not changed by tetrodotoxin (1 microM) but partially reduced by cyclo-(7-aminoheptanonyl-Phe-D-Trp-Lys-Thr[BZL]) (10 microM), a somatostatin antagonist. In conclusion, GABA enhances pancreatic exocrine secretion induced by secretagogues, which stimulate enzyme secretion predominantly, via GABA(A) receptors in the rat pancreas. The enhancing effect of GABA is partially mediated by inhibition of islet somatostatin release. GABA does not modify the activity of intrapancreatic neurons.

Temporal changes in neuronal activity of the bilateral medial vestibular nuclei following unilateral labyrinthectomy in rats

To investigate the changes in the responses of vestibular neurons with time during vestibular compensation, the resting activity and dynamic responses of type I and II neurons in the medial vestibular nuclei to sinusoidal angular acceleration were recorded following unilateral labyrinthectomy (ULX) in Sprague-Dawley rats. The unitary extracellular neuronal activity was recorded from the bilateral medial vestibular nuclei with stainless steel microelectrodes of 3~5 MOMEGA before ULX, and 6, 24, 48, 72 hours, and I week after ULX under pentobarbital sodium anesthesia (30 mg/kg, i.p.). Gain (spikes/s/deg/s) and phase (in degrees) were determined from the neuronal activity induced by sinusoidal head rotation with 0.05, 0.1, 0.2, and 0.4 Hz. The mean resting activity before ULX was 16.7+/-8.6 spikes/s in type I neurons (n=67, M+-SD) and 14.5+/-8.4 spikes/s in type II neurons (n=43). The activities of ipsilateral type I and contralateral type 11 neurons to the lesion side decreased markedly till 24 hr post-op, and a significant difference between ipsilateral and contralateral type I neurons sustained till 24 hr post-op. The gain at 4 different frequencies of sinusoidal rotation was depressed in all neurons till 6 or 24 hr post-op and then increased with time. The rate of decrease in gain was more prominent in ipsilateral type I and contralateral type 11 neurons immediately after ULX. Although the gain of those neurons increased gradually after 24 hours, it remained below normal levels. The phase was significantly advanced in all neurons following ULX. These results suggest that a depression of activities in ipsilateral type I and contralateral type II neurons is closely related with the occurrence of vestibular symptoms and restoration of activities in those neurons ameliorates the vestibular symptoms.