The Brain Cognition and Brain Disease Institute

Research news









1.论文标题:Hippocampal–prefrontalinput supports spatial encoding in working memory

原文摘要:Spatial working memory, the caching ofbehaviorally relevant spatial cues on a timescale of seconds, is a fundamental constituentof cognition. Although the prefrontal cortex and hippocampus are known tocontribute jointly to successful spatial working memory, the anatomical pathwayand temporal window for the interaction of these structures critical to spatialworking memory has not yet been established. Here we find that directhippocampal–prefrontal afferents are critical for encoding, but not formaintenance or retrieval, of spatial cues in mice. These cues are representedby the activity of individual prefrontal units in a manner that is dependent onhippocampal input only during the cue-encoding phase of a spatial workingmemory task. Successful encoding of these cues appears to be mediated bygamma-frequency synchrony between the two structures. These findings indicate acritical role for the direct hippocampal–prefrontal afferent pathway in thecontinuous updating of task-related spatial information during spatial workingmemory.



2.论文标题:Role of prefrontal cortex and the midbrain dopamine systemin working memory updating

原文摘要:Humans are adept at switching betweengoal-directed behaviors quickly and effectively. The prefrontal cortex (PFC) isthought to play a critical role by encoding, updating, and maintaining internalrepresentations of task context in working memory. It has also beenhypothesized that the encoding of context representations in PFC is regulatedby phasic dopamine gating signals. Here we use multimodal methods to test thesehypotheses. First we used functional MRI (fMRI) to identify regions of PFCassociated with the representation of context in a working memory task. Next weused single-pulse transcranial magnetic stimulation (TMS), guided spatially byour fMRI findings and temporally by previous event-related EEG recordings, todisrupt context encoding while participants performed the same working memorytask. We found that TMS pulses to the right dorsolateral PFC (DLPFC)immediately after context presentation, and well in advance of the response,adversely impacted context-dependent relative to context-independent responses.This finding causally implicates right DLPFC function in context encoding.Finally, using the same paradigm, we conducted high-resolution fMRImeasurements in brainstem dopaminergic nuclei (ventral tegmental area andsubstantia nigra) and found phasic responses after presentation of contextstimuli relative to other stimuli, consistent with the timing of a gatingsignal that regulates the encoding of representations in PFC. Furthermore,these responses were positively correlated with behavior, as well as with responsesin the same region of right DLPFC targeted in the TMS experiment, lendingsupport to the hypothesis that dopamine phasic signals regulate encoding, andthereby the updating, of context representations in PFC.



3.论文标题:Simulation of the capacity and precisionof working memory in the hypodopaminergic state: relevance toschizophrenia

论文摘要:Working memory (WM) impairment has receivedattention as a behavioral characteristic of schizophrenia. Neurobiologicalstudies have led to the hypothesis that a deficit in dopamine transmissionthrough D1 receptors in the prefrontal cortex (PFC) is associated with WMimpairment in schizophrenia. However, empirical approaches that aim to clarifythe nature of the impairment and its underlying mechanism are difficult toenact, especially in unmedicated patients. By contrast, computationalapproaches using biologically plausible models have formed a powerfultheoretical framework for the study of WM impairment in schizophrenia. Thisarticle attempts to directly connect neurobiological findings to theneuropsychological behaviors present in patients with schizophrenia. Using abiologically plausible prefrontal cortical circuit model, we simulatedsustained activity during a simultaneous, multitarget WM task. We subsequentlyanalyzed how dopaminergic modulation via D1 receptor activation alters thecapacity and precision of WM and investigated the underlying mechanism.Hypodopaminergic modulation resulted in imprecision and a reduced capacity inWM primarily due to decreased N-methyl-D-aspartate (NMDA) conductance.Increasing NMDA conductance ameliorated both impairments. These results accountfor the mechanism that underlies WM impairments in schizophrenia and provide atheoretical basis for combination therapy with antipsychotic drugs and drugsthat enhance NMDA receptor function, which is expected to be effective for thetreatment of WM impairments in these patients.