scholarly journals Hippocampal-Prefrontal cortex network dynamics predict performance during retrieval in a context-guided object memory task

2021 ◽  
Author(s):  
Juan Facundo Morici ◽  
Noelia Victoria Weisstaub ◽  
Camila Lidia Zold
Keyword(s):  
Prefrontal Cortex ◽  
Contextual Information ◽  
Phase Locking ◽  
Memory Task ◽  
Pyramidal Cells ◽  
Neuronal Ensembles ◽  
Electrophysiological Recordings ◽  
Specific Object ◽  
Underlying Mechanisms ◽  
Amplitude Correlation

Remembering life episodes is a complex process that requires the interaction between multiple brain areas. It is thought that contextual information provided by the hippocampus (HPC) can trigger the recall of a past event through the activation of medial prefrontal cortex (mPFC) neuronal ensembles, but the underlying mechanisms remain poorly understood. Indeed, little is known about how the vHPC and mPFC are coordinated during a contextual-guided recall of an object recognition memory. To address this, we performed electrophysiological recordings in behaving rats during the retrieval phase of the object-in-context memory task (OIC). Coherence, phase locking and theta amplitude correlation analysis showed an increase in vHPC-mPFC LFP synchronization in the theta range when animals explore contextually mismatched objects. Moreover, we identified ensembles of putative pyramidal cells in the mPFC that encode specific object-context associations. Interestingly, the increase of vHPC-mPFC synchronization during exploration of the contextually mismatched object and the preference of mPFC incongruent object neurons predicts the animal's performance during the resolution of the OIC task. Altogether, these results identify changes in vHPC-mPFC synchronization and mPFC ensembles encoding specific object-context associations likely involved in the recall of past events.

scholarly journals Mild metabolic stress is sufficient to disturb the formation of pyramidal cell ensembles during gamma oscillations

2019 ◽  
Vol 40 (12) ◽  
pp. 2401-2415 ◽  
Author(s):  
Shehabeldin Elzoheiry ◽  
Andrea Lewen ◽  
Justus Schneider ◽  
Martin Both ◽  
Dimitri Hefter ◽  
...  
Keyword(s):  
Pyramidal Cell ◽  
Metabolic Stress ◽  
Pyramidal Cells ◽  
Gamma Oscillations ◽  
System Level ◽  
Attention And Memory ◽  
Neuronal Ensembles ◽  
Brain Functions ◽  
Fast Spiking ◽  
Underlying Mechanisms

Disturbances of cognitive functions occur rapidly during acute metabolic stress. However, the underlying mechanisms are not fully understood. Cortical gamma oscillations (30–100 Hz) emerging from precise synaptic transmission between excitatory principal neurons and inhibitory interneurons, such as fast-spiking GABAergic basket cells, are associated with higher brain functions, like sensory perception, selective attention and memory formation. We investigated the alterations of cholinergic gamma oscillations at the level of neuronal ensembles in the CA3 region of rat hippocampal slice cultures. We combined electrophysiology, calcium imaging (CamKII.GCaMP6f) and mild metabolic stress that was induced by rotenone, a lipophilic and highly selective inhibitor of complex I in the respiratory chain of mitochondria. The detected pyramidal cell ensembles showing repetitive patterns of activity were highly sensitive to mild metabolic stress. Whereas such synchronised multicellular activity diminished, the overall activity of individual pyramidal cells was unaffected. Additionally, mild metabolic stress had no effect on the rate of action potential generation in fast-spiking neural units. However, the partial disinhibition of slow-spiking neural units suggests that disturbances of ensemble formation likely result from alterations in synaptic inhibition. Our study bridges disturbances on the (multi-)cellular and network level to putative cognitive impairment on the system level.

scholarly journals Multimodal determinants of phase-locked dynamics across deep-superficial hippocampal sublayers during theta oscillations

2020 ◽  
Author(s):  
Andrea Navas-Olive ◽  
Manuel Valero ◽  
Teresa Jurado-Parras ◽  
Adan de Salas-Quiroga ◽  
Robert G Averkin ◽  
...  
Keyword(s):  
Computational Models ◽  
Phase Locking ◽  
Memory Task ◽  
Pyramidal Cells ◽  
Theta Oscillations ◽  
Ca1 Pyramidal Cells ◽  
Cell Type Specific ◽  
High Level ◽  
Specific Phase ◽  
Phase Preference

Theta oscillations play a major role in temporarily defining the hippocampal rate code by translating behavioural sequences into neuronal representations. However, mechanisms constraining phase timing and cell-type specific phase preference are unknown. Here, we employ computational models tuned with evolutionary algorithms to evaluate phase preference of individual CA1 pyramidal cells recorded in mice and rats not engaged in any particular memory task. We applied unbiased and hypothesis-free approaches to identify effects of intrinsic and synaptic factors, as well as cell morphology, in determining phase preference. We found that perisomatic inhibition delivered by complementary populations of basket cells interacts with input pathways to shape phase-locked specificity of deep and superficial pyramidal cells. Somatodendritic integration of fluctuating glutamatergic inputs defined cycle-by-cycle by unsupervised methods demonstrated that firing selection is tuneable across sublayers. Our data identify different mechanisms of phase-locking selectivity that are instrumental for high-level flexible dynamical representations.

scholarly journals Pharmacological rescue of cognitive function in a mouse model of chemobrain

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Lien D. Nguyen ◽  
Tom T. Fischer ◽  
Barbara E. Ehrlich
Keyword(s):  
Cognitive Impairment ◽  
Prefrontal Cortex ◽  
Calcium Oscillations ◽  
Neuronal Morphology ◽  
Post Injection ◽  
Object Recognition Test ◽  
Cognitive Changes ◽  
Memory Acquisition ◽  
Underlying Mechanisms ◽  
Trisphosphate Receptor

Abstract Background After chemotherapy, many cancer survivors suffer from long-lasting cognitive impairment, colloquially known as “chemobrain.” However, the trajectories of cognitive changes and the underlying mechanisms remain unclear. We previously established paclitaxel-induced inositol trisphosphate receptor (InsP3R)-dependent calcium oscillations as a mechanism for peripheral neuropathy, which was prevented by lithium pretreatment. Here, we investigated if a similar mechanism also underlay paclitaxel-induced chemobrain. Method Mice were injected with 4 doses of 20 mg/kg paclitaxel every other day to induced cognitive impairment. Memory acquisition was assessed with the displaced object recognition test. The morphology of neurons in the prefrontal cortex and the hippocampus was analyzed using Golgi-Cox staining, followed by Sholl analyses. Changes in protein expression were measured by Western blot. Results Mice receiving paclitaxel showed impaired short-term spatial memory acquisition both acutely 5 days post injection and chronically 23 days post injection. Dendritic length and complexity were reduced in the hippocampus and the prefrontal cortex after paclitaxel injection. Concurrently, the expression of protein kinase C α (PKCα), an effector in the InsP3R pathway, was increased. Treatment with lithium before or shortly after paclitaxel injection rescued the behavioral, cellular, and molecular deficits observed. Similarly, memory and morphological deficits could be rescued by pretreatment with chelerythrine, a PKC inhibitor. Conclusion We establish the InsP3R calcium pathway and impaired neuronal morphology as mechanisms for paclitaxel-induced cognitive impairment. Our findings suggest lithium and PKC inhibitors as candidate agents for preventing chemotherapy-induced cognitive impairment.

The Effect of Divided Attention on Encoding and Retrieval in Episodic Memory Revealed by Positron Emission Tomography

2000 ◽  
Vol 12 (2) ◽  
pp. 267-280 ◽  
Author(s):  
Tetsuya Iidaka ◽  
Nicole D. Anderson ◽  
Shitij Kapur ◽  
Roberto Cabez ◽  
Fergus I. M. Craik
Keyword(s):  
Positron Emission Tomography ◽  
Prefrontal Cortex ◽  
Episodic Memory ◽  
Divided Attention ◽  
Memory Performance ◽  
Memory Task ◽  
Anterior Cingulate ◽  
Emission Tomography ◽  
Positron Emission ◽  
Encoding And Retrieval

The effects of divided attention (DA) on episodic memory encoding and retrieval were investigated in 12 normal young subjects by positron emission tomography (PET). Cerebral blood flow was measured while subjects were concurrently performing a memory task (encoding and retrieval of visually presented word pairs) and an auditory tone-discrimination task. The PET data were analyzed using multivariate Partial Least Squares (PLS), and the results revealed three sets of neural correlates related to specific task contrasts. Brain activity, relatively greater under conditions of full attention (FA) than DA, was identified in the occipital-temporal, medial, and ventral-frontal areas, whereas areas showing relatively more activity under DA than FA were found in the cerebellum, temporo-parietal, left anterior-cingulate gyrus, and bilateral dorsolateral-prefrontal areas. Regions more active during encoding than during retrieval were located in the hippocampus, temporal and the prefrontal cortex of the left hemisphere, and regions more active during retrieval than during encoding included areas in the medial and right-prefrontal cortex, basal ganglia, thalamus, and cuneus. DA at encoding was associated with specific decreases in rCBF in the left-prefrontal areas, whereas DA at retrieval was associated with decreased rCBF in a relatively small region in the right-prefrontal cortex. These different patterns of activity are related to the behavioral results, which showed a substantial decrease in memory performance when the DA task was performed at encoding, but no change in memory levels when the DA task was performed at retrieval.

scholarly journals Conjunctive representation of what and when in monkey hippocampus and lateral prefrontal cortex during an associative memory task

2019 ◽  
Author(s):  
Nathanael A. Cruzado ◽  
Zoran Tiganj ◽  
Scott L. Brincat ◽  
Earl K. Miller ◽  
Marc W. Howard
Keyword(s):  
Prefrontal Cortex ◽  
Associative Memory ◽  
Memory Task ◽  
Neural Recording ◽  
Temporal Coding ◽  
Adaptive Memory ◽  
Lateral Prefrontal Cortex ◽  
The Past ◽  
Large Numbers

AbstractAdaptive memory requires the organism to form associations that bridge between events separated in time. Many studies show interactions between hippocampus (HPC) and prefrontal cortex (PFC) during formation of such associations. We analyze neural recording from monkey HPC and PFC during a memory task that requires the monkey to associate stimuli separated by about a second in time. After the first stimulus was presented, large numbers of units in both HPC and PFC fired in sequence. Many units fired only when a particular stimulus was presented at a particular time in the past. These results indicate that both HPC and PFC maintain a temporal record of events that could be used to form associations across time. This temporal record of the past is a key component of the temporal coding hypothesis, a hypothesis in psychology that memory not only encodes what happened, but when it happened.

scholarly journals LSD induces increased signalling entropy in rats' prefrontal cortex

2021 ◽  
Author(s):  
Aurora Savino ◽  
Charles D Nichols
Keyword(s):  
Prefrontal Cortex ◽  
Molecular Level ◽  
Transcriptional Regulators ◽  
Cell Types ◽  
Rna Seq ◽  
Psychedelic Drugs ◽  
Underlying Mechanisms ◽  
Brain Entropy ◽  
New Compounds ◽  
Different Cell Types

Psychedelic drugs are gaining attention from the scientific community as potential new compounds for the treatment of psychiatric diseases such as mood and substance use disorders. The 5-HT2A receptor has been identified as the main molecular target, and early studies pointed to an effect on the expression of neuroplasticity genes. Analysing RNA-seq data from the prefrontal cortex of rats chronically treated with lysergic acid diethylamide (LSD), we describe the psychedelic-induced rewiring of gene co-expression networks, which become less centralized but more complex, with an overall increase in signalling entropy, typical of highly plastic systems. Intriguingly, signalling entropy mirrors, at the molecular level, the increased brain entropy reported through neuroimaging studies in human, suggesting the underlying mechanisms of higher-order phenomena. Moreover, from the analysis of network topology we identify potential transcriptional regulators and imply different cell types in psychedelics' activity.

scholarly journals Caffeine consumption during pregnancy accelerates the development of cognitive deficits in offspring in a model of tauopathy

2019 ◽  
Author(s):  
Stefania Zappettini ◽  
Emilie Faivre ◽  
Antoine Ghestem ◽  
Sébastien Carrier ◽  
Luc Buée ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Life ◽  
Pyramidal Cells ◽  
Tau Pathology ◽  
Caffeine Consumption ◽  
Early Life Exposure ◽  
Model Of Alzheimer’S Disease ◽  
Electrophysiological Recordings

AbstractPsychoactive drugs used during pregnancy can affect the development of the brain of offspring, directly triggering neurological disorders or increasing the risk for their occurrence. Caffeine is the most widely consumed psychoactive drug, including during pregnancy. In Wild type mice, early life exposure to caffeine renders offspring more susceptible to seizures. Here, we tested the long-term consequences of early life exposure to caffeine in THY-Tau22 transgenic mice, a model of Alzheimer’s disease-like Tau pathology. Caffeine exposed mutant offspring developed cognitive earlier than water treated mutants. Electrophysiological recordings of hippocampal CA1 pyramidal cells in vitro revealed that early life exposure to caffeine changed the way the glutamatergic and GABAergic drives were modified by the Tau pathology. We conclude that early-life exposure to caffeine affects the Tau phenotype and we suggest that caffeine exposure during pregnancy may constitute a risk-factor for early onset of Alzheimer’s disease-like pathology.

scholarly journals Prefrontal and Parietal Attractor Networks Mediate Working Memory Judgments

2020 ◽  
Author(s):  
Sihai Li ◽  
Christos Constantinidis ◽  
Xue-Lian Qi
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Dorsolateral Prefrontal Cortex ◽  
Critical Role ◽  
Memory Task ◽  
Delayed Response ◽  
Persistent Activity ◽  
Neural Basis ◽  
Brain Areas ◽  
Dorsolateral Prefrontal

ABSTRACTThe dorsolateral prefrontal cortex plays a critical role in spatial working memory and its activity predicts behavioral responses in delayed response tasks. Here we addressed whether this predictive ability extends to categorical judgments based on information retained in working memory, and is present in other brain areas. We trained monkeys in a novel, Match-Stay, Nonmatch-Go task, which required them to observe two stimuli presented in sequence with an intervening delay period between them. If the two stimuli were different, the monkeys had to saccade to the location of the second stimulus; if they were the same, they held fixation. Neurophysiological recordings were performed in areas 8a and 46 of the dlPFC and 7a and lateral intraparietal cortex (LIP) of the PPC. We hypothesized that random drifts causing the peak activity of the network to move away from the first stimulus location and towards the location of the second stimulus would result in categorical errors. Indeed, for both areas, when the first stimulus appeared in a neuron’s preferred location, the neuron showed significantly higher firing rates in correct than in error trials. When the first stimulus appeared at a nonpreferred location and the second stimulus at a preferred, activity in error trials was higher than in correct. The results indicate that the activity of both dlPFC and PPC neurons is predictive of categorical judgments of information maintained in working memory, and the magnitude of neuronal firing rate deviations is revealing of the contents of working memory as it determines performance.SIGNIFICANCE STATEMENTThe neural basis of working memory and the areas mediating this function is a topic of controversy. Persistent activity in the prefrontal cortex has traditionally been thought to be the neural correlate of working memory, however recent studies have proposed alternative mechanisms and brain areas. Here we show that persistent activity in both the dorsolateral prefrontal cortex and posterior parietal cortex predicts behavior in a working memory task that requires a categorical judgement. Our results offer support to the idea that a network of neurons in both areas act as an attractor network that maintains information in working memory, which informs behavior.

scholarly journals Separable actions of acetylcholine and noradrenaline on neuronal ensemble formation in hippocampal CA3 circuits

2021 ◽  
Vol 17 (10) ◽  
pp. e1009435
Author(s):  
Luke Y. Prince ◽  
Travis Bacon ◽  
Rachel Humphries ◽  
Krasimira Tsaneva-Atanasova ◽  
Claudia Clopath ◽  
...  
Keyword(s):  
Granule Cells ◽  
Mossy Fiber ◽  
Pyramidal Cells ◽  
Recurrent Network ◽  
Memory Storage ◽  
Neuronal Ensembles ◽  
Hippocampal Ca3 ◽  
Ca3 Pyramidal Cells ◽  
Episodic Memories ◽  
Mossy Fiber Pathway

In the hippocampus, episodic memories are thought to be encoded by the formation of ensembles of synaptically coupled CA3 pyramidal cells driven by sparse but powerful mossy fiber inputs from dentate gyrus granule cells. The neuromodulators acetylcholine and noradrenaline are separately proposed as saliency signals that dictate memory encoding but it is not known if they represent distinct signals with separate mechanisms. Here, we show experimentally that acetylcholine, and to a lesser extent noradrenaline, suppress feed-forward inhibition and enhance Excitatory–Inhibitory ratio in the mossy fiber pathway but CA3 recurrent network properties are only altered by acetylcholine. We explore the implications of these findings on CA3 ensemble formation using a hierarchy of models. In reconstructions of CA3 pyramidal cells, mossy fiber pathway disinhibition facilitates postsynaptic dendritic depolarization known to be required for synaptic plasticity at CA3-CA3 recurrent synapses. We further show in a spiking neural network model of CA3 how acetylcholine-specific network alterations can drive rapid overlapping ensemble formation. Thus, through these distinct sets of mechanisms, acetylcholine and noradrenaline facilitate the formation of neuronal ensembles in CA3 that encode salient episodic memories in the hippocampus but acetylcholine selectively enhances the density of memory storage.

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