I Retinal Structure and Information Coding

The retina is the first stage for visual information processing. The bottleneck structure in visual pathway makes one of the main function of retina is to highly compress visual information. Retinal ganglion cells mainly utilize adaptation and population activity to compress information. Our aim is to study how retina effectively processes and encodes visual information.

Research Focus:

1. The change of information encoded by RGCs during adaptation.
2. The role of population activity in visual information coding.
3. The influence of neural network on neuronal activity.
4. Build effective algorithms to process multi-dimensional data.

Visual System and Retinal Structure

Experimental System and Animals

Spike Detection and Sorting

Visual Stimulation Patterns

 

Concerted Activity

Concerted activity is widely observed in visual system. Concerted activity not only takes part in information encoding, but also plays important role in improving information transmission.

Different Types of Concerted Activity

The Influence of GABAergic Pathway on Concerted Activity

The Function of Concerted Activity

Adaptation Process

Visual system will modulate itself sensitivity when in exposure to different external environments, which is called adaptation. Many researches focus on how visual system utilizes adaptation to effectively process visual information

Types of Adaptation

The Change of Receptive Field during Contrast Adaptation

The Change of Synchronized Activity during Contrast Adaptation

Relationship between Receptive Field and Synchronized Activity

 

Information Coding

How to match neuronal activity with the information related to behavior is the basic question in neuroscience. When neurons transform external stimuli into action potentials, it not only transforms the form of energy, but also transforms the information included by stimuli into the spike sequences, which is the encoding process. These spike sequences are vital for central visual system to indentify external visual information.

References

Pu-Ming Zhang, Jin-Yong Wu, Yi Zhou, Pei-Ji Liang, Jing-Qi Yuan. Spike sorting based on automatic template reconstruction with a partial solution to the overlapping problem (2004). Journal of Neuroscience Methods 135: 55-65.
Guang-Li Wang, Yi Zhou, Ai-Hua Chen, Pu-Ming Zhang, Pei-Ji Liang. A robust method for spike sortin with automatic overlap decomposition (2006). IEEE Transaction on Biomedical Engineering 53: 1195-1198.
Xue Liu, Yi Zhou, Hai-Qing Gong, Pei-Ji Liang. Contribution of the GABAergic pathway(s) to the correlated activities of chicken retinal ganglion cells (2007). Brain Research 1177: 37-46.
Wei Jing, Wen-Zhong Liu, Xin-Wei Gong, Hai-Qing Gong, Pei-Ji Liang. Influence of GABAergic inhibition on concerted activity between the ganglion cells (2010). Neuroreport 21: 797-801.
Wei Jing, Wen-Zhong Liu, Xin-Wei Gong, Hai-Qing Gong, Pei-Ji Liang. Visual pattern recognition based on spatio-temporal patterns of retinal ganglion cells' activities (2010). Cognitive Neurodynamics 4: 179-188.
Ai-Hua Chen, Yi Zhou, Hai-Qing Gong, Pei-Ji Liang. Luminance adaptation increased the contrast sensitivity of retinal ganglion cells (2005). Neuroreport 16: 371-375.
Hao Li, Wen-Zhong Liu, Pei-Ji Liang. Adaptation-dependent synchronous activity contributes to receptive field size change of bullfrog retinal ganglion cell (2012), Plos One, 7: e34336.Lei Xiao, Dan-Ke Zhang, Yuan-Qing Li, Pei-Ji Liang, Si Wu. Adaptive neural information processing with dynamical electrical synapses (2013), Frontiers in Computational Neuroscience 7: 36.
Lei Xiao, Ming-Sha Zhang, Da-Jun Xing, Pei-Ji Liang, Si Wu. Shifted encoding strategy in retinal luminance adaptation: from firing rate to neural correlation. Journal of Neurophysiology (under review).

Activity Characteristics of Retinal Horizontal Cell

Horizontal cells are the GABAergic interneurons in the outer retina, which receive glutamate input from photoreceptors and provide negative feedback to photoreceptors. The glutamate receptors expressed on the horizontal cell's membrane are necessary for the generation of physiological functions of horizontal cells. Activation of glutamate receptors results in changes of membrane conductance, which can be most conveniently evaluated by patch-clamp techniques. Activation of glutamate receptors also results in elevation of intracellular calcium concentration. Calcium is one of the most versatile intracellular second messengers, which is known to be related to
a variety of cellular functions. We try to explore the physiological role of retinal cells in visual information processing by using both the calcium imaging and patch-clamp techniques.

Research Focus:

1. Subtypes, distribution, modulation, and physiological functions of the glutamate receptors on horizontal cells.
2. Modulation of GABA transporter current.
3. Subtypes, gating mechanisms, physiological functions, and modulation of ion channels expressed on horizontal cells。
4. Physiological functions of ER, and the mechanisms of release, depletion, and refilling of ER calcium.
5. Current and membrane potential dynamics under various physiological conditions.
……

Patch-clamp recording system Fluorescence microscopy imaging system Retinal horizontal cells

Subtypes, distribution, and modulation of the glutamate receptors

 

Modulation of GABA transporter current   Modulation of Zn2+on inward rectifying potassium currenet  

References

Shi-Yong Huang, Pei-Ji Liang. Ca2+-permeable and Ca2+-impermeable AMPA receptors coexist on horizontal cells (2005). Neuroreport 16: 263-266.
Yan Sun, Ya-Ting Zhang, Hai-Qing Gong, Pei-Ji Liang. The mechanisms of Zn2+effects on Ca2+- permeable AMPA receptors on carp retinal horizontal cells (2010). Brain Research 1345: 103-109.
Xiao-Dong Jiang, Xu-Long Wang, Yan Sun, Hai-Qing Gong, Pei-Ji Liang. NMDA modulation of GABA transporter current in carp retinal horizontal cells (2008). Brain Research 1240: 105-110.
Xiao-Dong Jiang, Yan Sun, Xu-Long Wang, Hai-Qing Gong, Pei-Ji Liang. Suppression of γ-aminobutyric acid transporter current by activation of ionotropic glutamate receptors on retinal horizontal cells (2009). Acta Physiologica
Sinica. 61(4): 299-304.
Ya-Ting Zhang, Yan Sun, Hai-Qing Gong, Pei-Ji Liang. Modulation of extracellular Zn2+on inward- rectifying potassium channel expressed on H1 type horizontal cell in carp retina (2011). Acta Biophysica Sinica. 27: 617-626.

Neural Modeling

In the research filed of neuroscience, the roles that computational neuroscience play becomes more and more important. In our Lab, based on the electrophysiological techniques in experiments, a large number of data are obtained. Except for the traditional processing and analysis methods in extracting information from the experimental data, some other approaches, e.g. model studies, may help us in further promoting and optimizing the experimental designs. In our Lab, the model studies are mainly concentrating on simulating how visual information are processed and transmitted in retinal circuit, and the corresponding models are constructed using the NEURON software (Fig. 1) and validated based on the experimental data we obtained. In the cross-subject research area involving neuroscience and information science, researches through biophysical neuronal models and neural circuits, can not only deepen our understandings in mechanisms mediate visual information processing, but also can promote the development of artificial visual systems, e.g. robotic vision system, and eventually embody their important implications in artificial intelligence.
In our previous studies, we have constructed a single compartment model of H1 type horizontal cell in carp retina using realistic ion channels, and have investigated the significant roles of NMDA receptors and GABA transporter current in modulating the concentrations of intracellular calcium. Using the electrophysiological data, we have compared the model results with our experimental observations, see Fig. 2 for more details. Specific descriptions of the H1 horizontal cell model are presented in (Wang et al., Neuroreport. 2008).
In addition, we have recorded some significant changes in the firing patterns of mouse retinal ganglion cells before and after the application of strychnine (an antagonist of glycine receptors) using multi-electrode arrays (MEA), and then, a simply retinal circuit was constructed, aiming to investigate how and where the changes occurred. Under a proper set of parameters, the constructed model can approximately reproduce the variations of ganglion cells’ firing patterns, and some potential circuit mechanisms are proposed, see Fig. 3 for more details.We will continue our studies based on the experimental data recorded by MEA, to further explore the population encoding strategies of retinal ganglion cells. Meanwhile, some computational neuronal models or neural circuits would be constructed, with the purpose of further expounding the effects of dynamic population activities in the processing and transmission of visual information, and to provide important clues in introducing some novel computational models and algorithm principles in the area of artificial intelligence.


II Epilepsy study, in vitro and in vivo

Hippoampal formation plays an important role during epileptogenesis of temporal lobe epilepsy. The electrophysiology characteristics of the hippocampal slices and the pilocarpine-induced epileptic mouse model are investigated by using multi-channel microelectrode recording techniques in vitro and in vivo . The epileptiform discharges from neurons are simultaneously recorded in hippocampus and some relevant regions. During epileptogenesis, the firing patterns of single and population neurons, correlation and causality of the firing activities of neurons in and among those regions are investigated. We try to figure out the characteristics and the clinical meaning of neural network firing activities during transition from inter-ictal to ictal discharging, and pharmacological effects of anti-epileptic drugs during the period prior to seizure. This project is an interdisciplinary study based on medicine and engineering. The results will help to provide biological evidences for the prevention and management of temporal lobe epilepsy and for the development of new anti-epileptic drugs.

Epileptiform discharges of the hippocampal structure

Being making up more than 40 percent, Temporal lobe epilepsy (TLE) is the most common type in adult patients with epilepsy. A large number of clinical observations and experimental studies are suggesting the important role that the hippocampus played in TLE. The goal of our work is to further study and explore the temporal and spatial characteristics as well as the underlying mechanism of the . We also want to investigate the mechanism of anti-epilepsy drugs (AEDs) on curing epilepsy and to seek for potential treatments.

Research Focus:

1. The temporal and spatial characteristics as well as other fundamental features of the epileptiform discharge in vitro by using the hippocampus of rats and mice.
2. The underlying mechanism causing epilepsy.
3. Effect and the action mechanisms of AEDs to epilepsy
4. To find potential anti-epileptic drugs and treatments.

hippocampal structure

The experimental system and specimens

The temporal and spatial characteristics of the epileptiform discharge

Effects of AEDs to the epileptiform discharge

References

Jian-Sheng Liu, Jing-Bo Li, Xin-Wei Gong, Hai-Qing Gong, Pu-Ming Zhang, Pei-Ji Liang, Qin-Chi Lu. Spatiotemporal dynamics of high-K+-induced epileptiform discharges in hippocampal slice and the effects of valproate (2013). Neuroscience Bulletin 29: 28–36.
Jing-Bo Li, Qin-Chi Lu, Xin-Wei Gong, Hai-Qing Gong, Pu-Ming Zhang, Pei-Ji Liang. The modulatory effects of exogenous Zn2+ on propagation and frequency of epileptiform discharges on rat hippocampal slices (2012). Acta Physiologica Sinica 28:119-130.
Fan Yang, Xin-Wei Gong, Hai-Qing Gong, Pu-Ming Zhang, Pei-Ji Liang, Qin-Chi Lu. Microelectrode array recordings of excitability of low Mg2+-induced acute hippocampal slices (2010), Neural Regeneration Research 5: 1548-1551.
Xin-Wei Gong, Fan Yang, Jian-Sheng Liu, Qin-Chi Lu, Hai-Qing Gong, Pei-Ji Liang, Pu-Ming Zhang. Investigation of the initiation site and propagation of epileptiform discharges in hippocampal slices using microelectrode array (2010). Progress in Biochemistry and Biophysics 37:1240-1247.
Jian-Sheng Liu, Xin-Wei Gong, Pu-Ming Zhang, Pei-Ji Liang, Qin-Chi Lu. Exploring spatiotemporal patterns of epileptiform discharge in hippocampal slice using multi-electrode arrays (2010). Acta Physiologica Sinica 62: 163-170.

Neural Network Dynamics during Development of Epilepsy

Research Focus:

1. The electrophysiological characters of neuronal activities in critical brain areas, such as hippocampus, entorhinal cortex, amygdaloidal nucleus, and thalamus.
2. The synchrony of the critical brain areas during the development of epilepsy.
……

Experimental system

Single-unit recordings

Local field potentials

Working hypothesis