scholarly journals NMDAr BLOCKING BY MK801 ALTERS HIPPOCAMPAL AND PREFRONTAL CORTEX OSCILLATIONS AND IMPAIRS SPATIAL WORKING MEMORY IN MICE.

2021 ◽  
Author(s):  
Pablo Abad-Perez ◽  
Luis M Martinez ◽  
Victor Borrell ◽  
Roger Redondo ◽  
Jorge R Brotons-Mas
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Spatial Working Memory ◽  
Dorsal Hippocampus ◽  
Gamma Oscillations ◽  
Oscillatory Activity ◽  
Y Maze ◽  
Spontaneous Exploration ◽  
New Treatments ◽  
And Behavior

Abnormal NMDAr function has been linked to rhythmopathies, psychosis, and cognitive dysfunction in schizophrenia. Here, we investigate the role of NMDAr hypofunction in pathological oscillations and behavior. We implanted mice with tetrodes in the dorsal hippocampus and medial prefrontal cortex (mPFC) and administered them with the NMDAr antagonist MK801, recording oscillations during spontaneous exploration in an open field and in the y-maze spatial working memory test. Our results show that NMDAr blockade increased locomotor activity and impaired spatial working memory. The administration of MK801 disrupted the correlation between oscillations and speed of movement, crucial for internal representations of distance. In the hippocampus, MK801 impaired gamma oscillations and theta/gamma coupling, while in the mPFC, it increased the power of theta, gamma, and generated high-frequency oscillations (HFO 155-185 Hz). Spatial working memory tests in the y-maze revealed that theta/gamma coupling was consistently higher in correct trials. Theta/gamma co-modulation mediated by NMDAr function might be key to explain various of schizophrenia's cognitive symptoms. Further investigating NMDAr hypofunction's role in the emergence of aberrant oscillatory activity will improve our understanding of schizophrenia and inspire new treatments of psychiatric disorders.

scholarly journals The role of prefrontal cortex in working memory: examining the contents of consciousness

1998 ◽  
Vol 353 (1377) ◽  
pp. 1819-1828 ◽  
Author(s):  
◽  
S. M. Courtney ◽  
L. Petit ◽  
J. V. Haxby ◽  
L. G. Ungerleider
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Visual Processing ◽  
Right Hemisphere ◽  
Functional Organization ◽  
Spatial Working Memory ◽  
Domain Specificity ◽  
Long Term Memory ◽  
Present Evidence ◽  
The Right

Working memory enables us to hold in our ‘mind's eye’ the contents of our conscious awareness, even in the absence of sensory input, by maintaining an active representation of information for a brief period of time. In this review we consider the functional organization of the prefrontal cortex and its role in this cognitive process. First, we present evidence from brain–imaging studies that prefrontal cortex shows sustained activity during the delay period of visual working memory tasks, indicating that this cortex maintains on–line representations of stimuli after they are removed from view. We then present evidence for domain specificity within frontal cortex based on the type of information, with object working memory mediated by more ventral frontal regions and spatial working memory mediated by more dorsal frontal regions. We also propose that a second dimension for domain specificity within prefrontal cortex might exist for object working memory on the basis of the type of representation, with analytic representations maintained preferentially in the left hemisphere and image–based representations maintained preferentially in the right hemisphere. Furthermore, we discuss the possibility that there are prefrontal areas brought into play during the monitoring and manipulation of information in working memory in addition to those engaged during the maintenance of this information. Finally, we consider the relationship of prefrontal areas important for working memory, both to posterior visual processing areas and to prefrontal areas associated with long–term memory.

scholarly journals Spatial Working Memory in Humans Depends on Theta and High Gamma Synchronization in the Prefrontal Cortex

2016 ◽  
Vol 26 (12) ◽  
pp. 1513-1521 ◽  
Author(s):  
Ivan Alekseichuk ◽  
Zsolt Turi ◽  
Gabriel Amador de Lara ◽  
Andrea Antal ◽  
Walter Paulus
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Spatial Working Memory ◽  
High Gamma

scholarly journals GSK3β inhibition restores cortical gamma oscillation and cognitive behavior in a mouse model of NMDA receptor hypofunction relevant to schizophrenia

2020 ◽  
Vol 45 (13) ◽  
pp. 2207-2218
Author(s):  
Kazuhito Nakao ◽  
Mahendra Singh ◽  
Kiran Sapkota ◽  
Bailey C. Hagler ◽  
Robert N. Hunter ◽  
...  
Keyword(s):  
Working Memory ◽  
Mouse Model ◽  
Spatial Working Memory ◽  
Gamma Oscillations ◽  
Gamma Oscillation ◽  
Mutant Mice ◽  
Patch Clamp Recording ◽  
Behavioral Deficits ◽  
Gamma Power ◽  
Sensory Evoked

Abstract Cortical gamma oscillations are believed to be involved in mental processes which are disturbed in schizophrenia. For example, the magnitudes of sensory-evoked oscillations, as measured by auditory steady-state responses (ASSRs) at 40 Hz, are robustly diminished, whereas the baseline gamma power is enhanced in schizophrenia. Such dual gamma oscillation abnormalities are also present in a mouse model of N-methyl-D-aspartate receptor hypofunction (Ppp1r2cre/Grin1 knockout mice). However, it is unclear whether the abnormal gamma oscillations are associated with dysfunction in schizophrenia. We found that glycogen synthase kinase-3 (GSK3) is overactivated in corticolimbic parvalbumin-positive GABAergic interneurons in Grin1 mutant mice. Here we addressed whether GSK3β inhibition reverses both abnormal gamma oscillations and behavioral deficits with high correlation by pharmacological and genetic approach. We demonstrated that the paralog selective-GSK3β inhibitor, but not GSK3α inhibitor, normalizes the diminished ASSRs, excessive baseline gamma power, and deficits in spatial working memory and prepulse inhibition (PPI) of acoustic startle in Grin1 mutant mice. Cell-type specific GSK3B knockdown, but not GSK3A knockdown, also reversed abnormal gamma oscillations and behavioral deficits. Moreover, GSK3B knockdown, but not GSK3A knockdown, reverses the mutants’ in vivo spike synchrony deficits. Finally, ex vivo patch-clamp recording from pairs of neighboring cortical pyramidal neurons showed a reduction of synchronous spontaneous inhibitory-postsynaptic-current events in mutants, which was reversed by GSK3β inhibition genetically and pharmacologically. Together, GSK3β inhibition in corticolimbic interneurons ameliorates the deficits in spatial working memory and PPI, presumably by restoration of synchronous GABA release, synchronous spike firing, and evoked-gamma power increase with lowered baseline power.

Prefrontal Task-Related Activity Representing Visual Cue Location or Saccade Direction in Spatial Working Memory Tasks

2002 ◽  
Vol 87 (1) ◽  
pp. 567-588 ◽  
Author(s):  
Kazuyoshi Takeda ◽  
Shintaro Funahashi
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Spatial Working Memory ◽  
Delay Period ◽  
Neuron Activity ◽  
Delayed Response ◽  
Related Activity ◽  
Visual Cue ◽  
Response Period ◽  
Dorsolateral Prefrontal

To examine what kind of information task-related activity encodes during spatial working memory processes, we analyzed single-neuron activity in the prefrontal cortex while two monkeys performed two different oculomotor delayed-response (ODR) tasks. In the standard ODR task, monkeys were required to make a saccade to the cue location after a 3-s delay, whereas in the rotatory ODR (R-ODR) task, they were required to make a saccade 90° clockwise from the cue location after the 3-s delay. By comparing the same task-related activities in these two tasks, we could determine whether such activities encoded the location of the visual cue or the direction of the saccade. One hundred twenty one neurons exhibited task-related activity in relation to at least one task event in both tasks. Among them, 41 neurons exhibited directional cue-period activity, most of which encoded the location of the visual cue. Among 56 neurons with directional delay-period activity, 86% encoded the location of the visual cue, whereas 13% encoded the direction of the saccade. Among 57 neurons with directional response-period activity, 58% encoded the direction of the saccade, whereas 35% encoded the location of the visual cue. Most neurons whose response-period activity encoded the location of the visual cue also exhibited directional delay-period activity that encoded the location of the visual cue as well. The best directions of these two activities were identical, and most of these response-period activities were postsaccadic. Therefore this postsaccadic activity can be considered a signal to terminate unnecessary delay-period activity. Population histograms encoding the location of the visual cue showed tonic sustained activation during the delay period. However, population histograms encoding the direction of the saccade showed a gradual increase in activation during the delay period. These results indicate that the transformation from visual input to motor output occurs in the dorsolateral prefrontal cortex. The analysis using population histograms suggests that this transformation occurs gradually during the delay period.

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