Xiaping Xie

NMDA Receptor-dependent LTD in different subfields of hippocampus in vivo and in vitro

In simulations with artificial neural networks, efficient information processing and storage has been shown to require that the strength of connections between network elements has the capacity to both increase and decrease in a use‐dependent manner. In contrast to long‐term potentiation (LTP) of excitatory synaptic transmission, activity‐dependent long‐term depression (LTD) has been difficult to demonstrate in forebrain in vivo. Theoretical arguments indicate that coincidence of presynaptic excitation and low‐magnitude postsynaptic activation are the necessary prerequisites for LTD induction. Here we report that stimulation paradigms which cause 1) sufficient excitation to result in NMDA receptor activation and simultaneously 2) attenuate the level of postsynaptic activation by recruitment of GABAA receptor‐mediated inhibition consistently produce LTD of commissural input to area CA1 in the hippocampus of anesthetized adult rats, and of the perforant path input to the dentate gyrus in the hippocampus of anesthetized and unanesthetized adult rabbits. A functionally similar pre‐ and postsynaptic activation pattern applied to the hippocampal slice preparation by injecting hyperpolarizing current into the postsynaptic cell during NMDA receptor‐mediated excitation also was effective in consistently inducing LTD. Results of studies in vitro show that Ca2+ influx through the NMDA channel is necessary for the induction of LTD, and moreover, that NMDA receptors also participate in the expression of LTD. Our findings demonstrate a general mechanism for the implementation of a theoretically derived learning rule in adult forebrain in vivo and in vitro and provide justification for the inclusion of use‐dependent decreases of connection weights in formal models of cognitive processing.

Differential Effect of TEA on Long-Term Synaptic Modification in Hippocampal CA1 and Dentate Gyrus in vitro

The effectiveness of tetraethylammonium (TEA) and high-frequency stimulation (HFS) in inducing long-term synaptic modification is compared in CA1 and dentate gyrus (DG) in vitro. High-frequency stimulation induces long-term potentiation (LTP) at synapses of both perforant path-DG granule cell and Schaffer collateral-CA1 pyramidal cell pathways. By contrast, TEA (25 mM) induces long-term depression in DG while inducing LTP in CA1. The mechanisms underlying the differential effect of TEA in CA1 and DG were investigated. It was observed that T-type voltage-dependent calcium channel (VDCC) blocker, Ni2+ (50 microM), partially blocked TEA-induced LTP in CA1. A complete blockade of the TEA-induced LTP occurred when Ni2+ was applied together with the NMDA receptor antagonist, D-APV. The L-type VDCC blocker, nifidipine (20 microM), had no effect on CA1 TEA-induced LTP. In DG of the same slice, TEA actually induced long-term depression (LTD) instead of LTP, an effect that was blocked by D-APV. Neither T-type nor L-type VDCC blockade could prevent this LTD. When the calcium concentration in the perfusion medium was increased, TEA induced a weak LTP in DG that was blocked by Ni2+. During exposure to TEA, the magnitude of field EPSPs was increased in both CA1 and DG, but the increase was substantially greater in CA1. Tetraethylammonium application also was associated with a large, late EPSP component in CA1 that persisted even after severing the connections between CA3 and CA1. All of the TEA effects in CA1, however, were dramatically reduced by Ni2+. The results of this study indicate that TEA indirectly acts via both T-type VDCCs and NMDA receptors in CA1 and, as a consequence, induces LTP. By contrast, TEA indirectly acts via only NMDA receptors in DG and results in LTD. The results raise the possibility of a major synaptic difference in the density and/or distribution of T-type VDCCs and NMDA receptors in CA1 and DG of the rat hippocampus.

Experimental Basis for an Input/Output Model of the Hippocampal Formation

This chapter focuses on the problem of developing biologically realistic models of complex neural systems typical of those found in the mammalian brain. In a specific application to the hippocampus, it is demonstrated that the nonlinear dynamics of the system and its elements can be determined experimentally by electrically stimulating its major intrinsic afferents with an input that approximates a Poisson process. Through cross-correlation techniques, the input/output properties of the neural elements tested can be modeled as the kernels of a functional power series. Experimental elimination of feedforward and feedback pathways is used to study progressively more elemental units of the system, eventually allowing the characterization of nonlinear response characteristics of individual neurons in an open-loop condition. A strategy for extending this approach to obtain a representation of the global system is described.

A protocol-based simulation for linking computational and experimental studies

Abstract An integrated approach has been developed to facilitate the coupling of computational and empirical neuroscience by employing methodologies of simulation and experimental studies to provide a common language for these two disciplines to communicate. The core of the simulation tools (EONS, Elementary Objects of Neural Systems) is an object-oriented library comprising of neural models, from networks, neurons, synapses, down to molecules in a hierarchical structure. A protocol-based scheme is adopted by both the simulation and the neurobiological database which stores the information about the experiments to provide the linkage.

EONS: A Multi-Level Modeling System and Its Applications

Publisher Summary Elementary objects of nervous system (EONS) are used to provide a framework for representing structural relationships and functional interactions among different levels of neural organization. In EONS, object-oriented design methodology is adopted to form a hierarchy of neural models from molecules, synapses, and neurons to networks. This chapter discusses the EONS object library, as well as two example models to illustrate the principles and functionalities of EONS. It also describes a protocol-based simulation scheme and the future development of EONS. Using object-oriented design methodology, projects have been developed for different neural components, from networks, neurons, dendrites, and synapses right down to molecules. Synapse, the contact between neurons, is a complex system composed of a multitude of molecular machinery. A model of partitioned synapses is developed to study the impact of structural modifications on neurotransmitter release and synaptic dynamics. The process of neurotransmitter release is dynamically mediated by complex molecular and cellular mechanisms. Speech recognition from unprocessed, noisy raw waveforms of words spoken by multiple speakers with a simple neural network, consisting of a small number of neurons connected by dynamic synapse, is discussed in this chapter.