Banna Biomedical Research Institute

Yunnan, China

Banna Biomedical Research Institute

Yunnan, China

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Tsien J.Z.,Georgia Regents University | Tsien J.Z.,Banna Biomedical Research Institute
Frontiers in Systems Neuroscience | Year: 2016

Humans and animals may encounter numerous events, objects, scenes, foods and countless social interactions in a lifetime. This means that the brain is constructed by evolution to deal with uncertainties and various possibilities. What is the architectural abstraction of intelligence that enables the brain to discover various possible patterns and knowledge about complex, evolving worlds? Here, I discuss the Theory of Connectivity–a “power-of-two” based, operational principle that can serve as a unified wiring and computational logic for organizing and constructing cell assemblies into the microcircuit-level building block, termed as functional connectivity motif(FCM). Defined by the power-of-two based equation, N = 2i−1, each FCM consists of the principal projection neuron cliques (N), ranging from those specific cliques receiving specific information inputs (i) to those general and sub-general cliques receiving various combinatorial convergent inputs. As the evolutionarily conserved logic, its validation requires experimental demonstrations of the following three major properties: (1) Anatomical prevalence—FCMs are prevalent across neural circuits, regardless of gross anatomical shapes; (2) Species conservancy—FCMs are conserved across different animal species; and (3) Cognitive universality—FCMs serve as a universal computational logic at the cell assembly level for processing a variety of cognitive experiences and flexible behaviors. More importantly, this Theory of Connectivity further predicts that the specific-to-general combinatorial connectivity pattern within FCMs should be preconfigured by evolution, and emerge innately from development as the brain’s computational primitives. This proposed design-principle can also explain the general purpose of the layered cortex and serves as its core computational algorithm. © 2016 Tsien.


Xie K.,Georgia Regents University | Xie K.,Banna Biomedical Research Institute | Kuang H.,Georgia Regents University | Kuang H.,Banna Biomedical Research Institute | Tsien J.Z.,Georgia Regents University
PLoS ONE | Year: 2013

There is a general interest in understanding of whether and how exposure to emotionally traumatizing events can alter memory function and anxiety behaviors. Here we have developed a novel laboratory-version of mild blast exposure comprised of high decibel bomb explosion sound coupled with strong air blast to mice. This model allows us to isolate the effects of emotionally fearful components from those of traumatic brain injury or bodily injury typical associated with bomb blasts. We demonstrate that this mild blast exposure is capable of impairing object recognition memory, increasing anxiety in elevated O-maze test, and resulting contextual generalization. Our in vivo neural ensemble recording reveal that such mild blast exposures produced diverse firing changes in the anterior cingulate cortex, a region processing emotional memory and inhibitory control. Moreover, we show that these real-time neural ensemble patterns underwent post-event reverberations, indicating rapid consolidation of those fearful experiences. Identification of blast-induced neural activity changes in the frontal brain may allow us to better understand how mild blast experiences result in abnormal changes in memory functions and excessive fear generalization related to post-traumatic stress disorder. © 2013 Xie et al.


Zhao F.,Georgia Regents University | Zhao F.,BanNa Biomedical Research Institute | Li M.,Georgia Regents University | Qian Y.,BanNa Biomedical Research Institute | Tsien J.Z.,Georgia Regents University
PLoS ONE | Year: 2013

Non-contact and low-cost measurements of heart and respiration rates are highly desirable for telemedicine. Here, we describe a novel technique to extract blood volume pulse and respiratory wave from a single channel images captured by a video camera for both day and night conditions. The principle of our technique is to uncover the temporal dynamics of heart beat and breathing rate through delay-coordinate transformation and independent component analysis-based deconstruction of the single channel images. Our method further achieves robust elimination of false positives via applying ratio-variation probability distributions filtering approaches. Moreover, it enables a much needed low-cost means for preventing sudden infant death syndrome in new born infants and detecting stroke and heart attack in elderly population in home environments. This noncontact-based method can also be applied to a variety of animal model organisms for biomedical research. © 2013 Zhao et al.


Wang D.,Banna Biomedical Research Institute | Jacobs S.A.,Georgia Regents University | Tsien J.Z.,Georgia Regents University
Expert Opinion on Therapeutic Targets | Year: 2014

Introduction: Age-related memory loss is believed to be a result of reduced synaptic plasticity, including changes in the NR2 subunit composition of the NMDA receptor. It is known that endogenous NR2B subunits decrease as the brain ages, whereas transgenic upregulation of NR2B enhances synaptic plasticity and learning and memory in several animal species. Accumulating evidence suggests that elevated brain magnesium levels, via dietary supplementation, can boost NR2B in the brain, consequently reversing memory deficits and enhancing cognitive abilities.Areas covered: This review highlights the convergent molecular mechanisms via the NR2B pathway as a useful strategy for treating age-related memory loss. A dietary approach, via oral intake of a novel compound, magnesium L-threonate (MgT), to boost NR2B expression in the brain is highlighted.Expert opinion: Direct upregulation of the NR2B subunit expression can enhance synaptic plasticity and memory functions in a broad range of behavioral tasks in rodents. Other upregulation approaches, such as targeting the NR2B transporter or surface recycling pathway via cyclin-dependent kinase 5, are highly effective in improving memory functions. A dietary supplemental approach by optimally elevating the [Mg2+] in the brain is surprisingly effective in upregulating NR2B expression and improving memories in preclinical studies. MgT is currently under clinical trials. © Informa UK, Ltd.


Mei B.,East China Normal University | Mei B.,University of Georgia | Li F.,Shanghai JiaoTong University | Li F.,University of Georgia | And 4 more authors.
PLoS ONE | Year: 2011

Pattern completion, the ability to retrieve complete memories initiated by subsets of external cues, has been a major focus of many computation models. A previously study reports that such pattern completion requires NMDA receptors in the hippocampus. However, such a claim was derived from a non-inducible gene knockout experiment in which the NMDA receptors were absent throughout all stages of memory processes as well as animal's adult life. This raises the critical question regarding whether the previously described results were truly resulting from the requirement of the NMDA receptors in retrieval. Here, we have examined the role of the NMDA receptors in pattern completion via inducible knockout of NMDA receptors limited to the memory retrieval stage. By using two independent mouse lines, we found that inducible knockout mice, lacking NMDA receptor in either forebrain or hippocampus CA1 region at the time of memory retrieval, exhibited normal recall of associative spatial reference memory regardless of whether retrievals took place under full-cue or partial-cue conditions. Moreover, systemic antagonism of NMDA receptor during retention tests also had no effect on full-cue or partial-cue recall of spatial water maze memories. Thus, both genetic and pharmacological experiments collectively demonstrate that pattern completion during spatial associative memory recall does not require the NMDA receptor in the hippocampus or forebrain. © 2011 Mei et al.


Liu J.,East China Normal University | Liu J.,Georgia Regents University | Wei W.,East China Normal University | Wei W.,Georgia Regents University | And 6 more authors.
PLoS ONE | Year: 2013

Heart physiology is a highly useful indicator for measuring not only physical states, but also emotional changes in animals. Yet changes of heart rate variability during fear conditioning have not been systematically studied in mice. Here, we investigated changes in heart rate and heart rate variability in both short-term and long-term contextual and cued fear conditioning. We found that while fear conditioning could increase heart rate, the most significant change was the reduction in heart rate variability which could be further divided into two distinct stages: a highly rhythmic phase (stage-I) and a more variable phase (stage-II). We showed that the time duration of the stage-I rhythmic phase were sensitive enough to reflect the transition from short-term to long-term fear memories. Moreover, it could also detect fear extinction effect during the repeated tone recall. These results suggest that heart rate variability is a valuable physiological indicator for sensitively measuring the consolidation and expression of fear memories in mice. © 2013 Liu et al.


Zhang H.,Georgia Regents University | Chen G.,Georgia Regents University | Kuang H.,Georgia Regents University | Kuang H.,Banna Biomedical Research Institute | Tsien J.Z.,Georgia Regents University
PLoS ONE | Year: 2013

Mapping and decoding brain activity patterns underlying learning and memory represents both great interest and immense challenge. At present, very little is known regarding many of the very basic questions regarding the neural codes of memory: are fear memories retrieved during the freezing state or non-freezing state of the animals? How do individual memory traces give arise to a holistic, real-time associative memory engram? How are memory codes regulated by synaptic plasticity? Here, by applying high-density electrode arrays and dimensionality-reduction decoding algorithms, we investigate hippocampal CA1 activity patterns of trace fear conditioning memory code in inducible NMDA receptor knockout mice and their control littermates. Our analyses showed that the conditioned tone (CS) and unconditioned footshock (US) can evoke hippocampal ensemble responses in control and mutant mice. Yet, temporal formats and contents of CA1 fear memory engrams differ significantly between the genotypes. The mutant mice with disabled NMDA receptor plasticity failed to generate CS-to-US or US-to-CS associative memory traces. Moreover, the mutant CA1 region lacked memory traces for "what at when" information that predicts the timing relationship between the conditioned tone and the foot shock. The degraded associative fear memory engram is further manifested in its lack of intertwined and alternating temporal association between CS and US memory traces that are characteristic to the holistic memory recall in the wild-type animals. Therefore, our study has decoded real-time memory contents, timing relationship between CS and US, and temporal organizing patterns of fear memory engrams and demonstrated how hippocampal memory codes are regulated by NMDA receptor synaptic plasticity. © 2013 Zhang et al.


Jacobs S.,Georgia Regents University | Cui Z.,Georgia Regents University | Feng R.,Georgia Regents University | Wang H.,East China Normal University | And 2 more authors.
PLoS ONE | Year: 2014

The opening-duration of the NMDA receptors implements Hebb's synaptic coincidence-detection and is long thought to be the rate-limiting factor underlying superior memory. Here, we investigate the molecular and genetic determinants of the NMDA receptors by testing the "synaptic coincidence-detection time-duration" hypothesis vs. "GluN2B intracellular signaling domain" hypothesis. Accordingly, we generated a series of GluN2A, GluN2B, and GluN2D chimeric subunit transgenic mice in which C-terminal intracellular domains were systematically swapped and overexpressed in the forebrain excitatory neurons. The data presented in the present study supports the second hypothesis, the "GluN2B intracellular signaling domain" hypothesis. Surprisingly, we found that the voltage-gated channel opening-durations through either GluN2A or GluN2B are sufficient and their temporal differences are marginal. In contrast, the C-terminal intracellular domain of the GluN2B subunit is necessary and sufficient for superior performances in long-term novel object recognition and cued fear memories and superior flexibility in fear extinction. Intriguingly, memory enhancement correlates with enhanced longterm potentiation in the 10-100 Hz range while requiring intact long-term depression capacity at the 1-5 Hz range. © 2014 Jacobs et al.


PubMed | East China Normal University, Georgia Regents University and Banna Biomedical Research Institute
Type: Journal Article | Journal: PloS one | Year: 2014

The opening-duration of the NMDA receptors implements Hebbs synaptic coincidence-detection and is long thought to be the rate-limiting factor underlying superior memory. Here, we investigate the molecular and genetic determinants of the NMDA receptors by testing the synaptic coincidence-detection time-duration hypothesis vs. GluN2B intracellular signaling domain hypothesis. Accordingly, we generated a series of GluN2A, GluN2B, and GluN2D chimeric subunit transgenic mice in which C-terminal intracellular domains were systematically swapped and overexpressed in the forebrain excitatory neurons. The data presented in the present study supports the second hypothesis, the GluN2B intracellular signaling domain hypothesis. Surprisingly, we found that the voltage-gated channel opening-durations through either GluN2A or GluN2B are sufficient and their temporal differences are marginal. In contrast, the C-terminal intracellular domain of the GluN2B subunit is necessary and sufficient for superior performances in long-term novel object recognition and cued fear memories and superior flexibility in fear extinction. Intriguingly, memory enhancement correlates with enhanced long-term potentiation in the 10-100 Hz range while requiring intact long-term depression capacity at the 1-5 Hz range.


PubMed | Banna Biomedical Research Institute
Type: Journal Article | Journal: Expert opinion on therapeutic targets | Year: 2014

Age-related memory loss is believed to be a result of reduced synaptic plasticity, including changes in the NR2 subunit composition of the NMDA receptor. It is known that endogenous NR2B subunits decrease as the brain ages, whereas transgenic upregulation of NR2B enhances synaptic plasticity and learning and memory in several animal species. Accumulating evidence suggests that elevated brain magnesium levels, via dietary supplementation, can boost NR2B in the brain, consequently reversing memory deficits and enhancing cognitive abilities.This review highlights the convergent molecular mechanisms via the NR2B pathway as a useful strategy for treating age-related memory loss. A dietary approach, via oral intake of a novel compound, magnesium L-threonate (MgT), to boost NR2B expression in the brain is highlighted.Direct upregulation of the NR2B subunit expression can enhance synaptic plasticity and memory functions in a broad range of behavioral tasks in rodents. Other upregulation approaches, such as targeting the NR2B transporter or surface recycling pathway via cyclin-dependent kinase 5, are highly effective in improving memory functions. A dietary supplemental approach by optimally elevating the [Mg] in the brain is surprisingly effective in upregulating NR2B expression and improving memories in preclinical studies. MgT is currently under clinical trials.

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