@article{5828,
  abstract     = {Hippocampus is needed for both spatial working and reference memories. Here, using a radial eight-arm maze, we examined how the combined demand on these memories influenced CA1 place cell assemblies while reference memories were partially updated. This was contrasted with control tasks requiring only working memory or the update of reference memory. Reference memory update led to the reward-directed place field shifts at newly rewarded arms and to the gradual strengthening of firing in passes between newly rewarded arms but not between those passes that included a familiar-rewarded arm. At the maze center, transient network synchronization periods preferentially replayed trajectories of the next chosen arm in reference memory tasks but the previously visited arm in the working memory task. Hence, reference memory demand was uniquely associated with a gradual, goal novelty-related reorganization of place cell assemblies and with trajectory replay that reflected the animal's decision of which arm to visit next.},
  author       = {Xu, Haibing and Baracskay, Peter and O'Neill, Joseph and Csicsvari, Jozsef L},
  issn         = {10974199},
  journal      = {Neuron},
  number       = {1},
  pages        = {119--132.e4},
  publisher    = {Elsevier},
  title        = {{Assembly responses of hippocampal CA1 place cells predict learned behavior in goal-directed spatial tasks on the radial eight-arm maze}},
  doi          = {10.1016/j.neuron.2018.11.015},
  volume       = {101},
  year         = {2019},
}

@phdthesis{837,
  abstract     = {The hippocampus is a key brain region for memory and notably for spatial memory, and is needed for both spatial working and reference memories. Hippocampal place cells selectively discharge in specific locations of the environment to form mnemonic represen tations of space. Several behavioral protocols have been designed to test spatial memory which requires the experimental subject to utilize working memory and reference memory. However, less is known about how these memory traces are presented in the hippo campus, especially considering tasks that require both spatial working and long -term reference memory demand. The aim of my thesis was to elucidate how spatial working memory, reference memory, and the combination of both are represented in the hippocampus. In this thesis, using a radial eight -arm maze, I examined how the combined demand on these memories influenced place cell assemblies while reference memories were partially updated by changing some of the reward- arms. This was contrasted with task varian ts requiring working or reference memories only. Reference memory update led to gradual place field shifts towards the rewards on the switched arms. Cells developed enhanced firing in passes between newly -rewarded arms as compared to those containing an unchanged reward. The working memory task did not show such gradual changes. Place assemblies on occasions replayed trajectories of the maze; at decision points the next arm choice was preferentially replayed in tasks needing reference memory while in the pure working memory task the previously visited arm was replayed. Hence trajectory replay only reflected the decision of the animal in tasks needing reference memory update. At the reward locations, in all three tasks outbound trajectories of the current arm were preferentially replayed, showing the animals’ next path to the center. At reward locations trajectories were replayed preferentially in reverse temporal order. Moreover, in the center reverse replay was seen in the working memory task but in the other tasks forward replay was seen. Hence, the direction of reactivation was determined by the goal locations so that part of the trajectory which was closer to the goal was reactivated later in an HSE while places further away from the goal were reactivated earlier. Altogether my work demonstrated that reference memory update triggers several levels of reorganization of the hippocampal cognitive map which are not seen in simpler working memory demand s. Moreover, hippocampus is likely to be involved in spatial decisions through reactivating planned trajectories when reference memory recall is required for such a decision. },
  author       = {Xu, Haibing},
  issn         = {2663-337X},
  pages        = {93},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Reactivation of the hippocampal cognitive map in goal-directed spatial tasks}},
  doi          = {10.15479/AT:ISTA:th_858},
  year         = {2017},
}

@article{6198,
  abstract     = {Stroke is a major public health problem leading to high rates of death and disability in adults. Excessive stimulation of N-methyl-D-aspartate receptors (NMDARs) and the resulting neuronal nitric oxide synthase (nNOS) activation are crucial for neuronal injury after stroke insult. However, directly inhibiting NMDARs or nNOS can cause severe side effects because they have key physiological functions in the CNS. Here we show that cerebral ischemia induces the interaction of nNOS with postsynaptic density protein-95 (PSD-95). Disrupting nNOS-PSD-95 interaction via overexpressing the N-terminal amino acid residues 1-133 of nNOS (nNOS-N(1-133)) prevented glutamate-induced excitotoxicity and cerebral ischemic damage. Given the mechanism of nNOS-PSD-95 interaction, we developed a series of compounds and discovered a small-molecular inhibitor of the nNOS-PSD-95 interaction, ZL006. This drug blocked the ischemia-induced nNOS-PSD-95 association selectively, had potent neuroprotective activity in vitro and ameliorated focal cerebral ischemic damage in mice and rats subjected to middle cerebral artery occlusion (MCAO) and reperfusion. Moreover, it readily crossed the blood-brain barrier, did not inhibit NMDAR function, catalytic activity of nNOS or spatial memory, and had no effect on aggressive behaviors. Thus, this new drug may serve as a treatment for stroke, perhaps without major side effects. },
  author       = {Zhou, L and Li, F and Xu, Haibing and Luo, CX and Wu, HY and Zhu, MM and Lu, W and Ji, X and Zhou, QG and Zhu, DY},
  issn         = {1078-8956},
  journal      = {Nature Medicine},
  number       = {12},
  pages        = {1439--1443},
  publisher    = {Nature Publishing Group},
  title        = {{Treatment of cerebral ischemia by disrupting ischemia-induced interaction of nNOS with PSD-95}},
  doi          = {10.1038/nm.2245},
  volume       = {16},
  year         = {2010},
}