Memory Maintenance Research Articles

Working memory-related alterations in neural oscillations reveal the influence of in-vehicle toluene on cognition at low concentration.

Although toluene is a typical in-vehicle pollutant, the impacts of in-vehicle toluene exposure on cognitive functions remain unestablished. Therefore, this study aimed to investigate the effects of short-term toluene exposure in vehicles on working memory based on neural oscillations. In total, 24 healthy adults were recruited. Each subject was exposed to four different concentrations of toluene and divided into 0ppb, 17.5ppb, 35ppb, and 70ppb groups for self-control studies. After 4h of exposure to each concentration of toluene, a behavioral test of visual working memory was performed while 19-channel electroencephalogram (EEG) signals were collected. Meanwhile, the power spectral density (PSD) and spatial distribution of working memory encoding, maintenance, and extraction periods were calculated by short-time Fourier transform to clarify the characteristic frequency bands, major brain regions, and characteristic channels of each period. To compare the changes in the characteristic patterns of neural oscillations under the effect of different concentrations of toluene. There was no significant difference in working memory reaction time and correct rate between the groups at different toluene concentrations (p > 0.05). The characteristic frequency band of the working memory neural oscillations in each group was the theta frequency band; the PSD of the theta frequency band was predominantly concentrated in the frontal area, and the characteristic channel was the Fz channel. The whole brain (F = 3.817, p < 0.05; F = 4.758, p < 0.01; F = 3.694, p < 0.05), the frontal area (F = 2.505, p < 0.05; F = 2.839, p < 0.05; F = 6.068, p < 0.05), the Fz channel (F = 3.522, p < 0.05; F = 3.745, p < 0.05; F = 6.526, p < 0.05), and the PSD of working memory in the theta frequency band was significantly increased in the 70ppb group compared with the other three groups during the coding, maintenance, and retrieval phases of working memory. When the in-vehicle toluene exposure concentration was 70ppb, the PSD of the characteristic frequency bands of working memory was significantly increased in the whole brain, major brain regions, and characteristic channels.

Novel prokaryotic system employing previously unknown nucleic acids-based receptors

The present study describes a previously unknown universal system that orchestrates the interaction of bacteria with the environment, named the Teazeled receptor system (TR-system). The identical system was recently discovered within eukaryotes. The system includes DNA- and RNA-based molecules named “TezRs”, that form receptor’s network located outside the membrane, as well as reverse transcriptases and integrases. TR-system takes part in the control of all major aspects of bacterial behavior, such as intra cellular communication, growth, biofilm formation and dispersal, utilization of nutrients including xenobiotics, virulence, chemo- and magnetoreception, response to external factors (e.g., temperature, UV, light and gas content), mutation events, phage-host interaction, and DNA recombination activity. Additionally, it supervises the function of other receptor-mediated signaling pathways. Importantly, the TR-system is responsible for the formation and maintenance of cell memory to preceding cellular events, as well the ability to “forget” preceding events. Transcriptome and biochemical analysis revealed that the loss of different TezRs instigates significant alterations in gene expression and proteins synthesis.

A critical role for long-term potentiation mechanisms in the maintenance of object recognition memory in perirhinal cortex revealed by the infusion of zeta inhibitory pseudosubstrate.

Object recognition, the ability to discriminate between a novel and a familiar stimulus, is critically dependent upon the perirhinal cortex. Neural response reductions upon repetition of a stimulus, have been hypothesized to be the mechanism within perirhinal cortex that supports recognition memory function. Thus, investigations into the mechanisms of long-term depression (LTD) in perirhinal cortex has provided insight into the mechanism of object recognition memory formation, but the contribution of long-term potentiation (LTP) to object recognition memory formation has been less studied. Inhibition of atypical PKC activity by Zeta Inhibitory Pseudosubstrate (ZIP) impairs the maintenance of LTP but not LTD, thus here infusion of ZIP into the perirhinal cortex allowed us to investigate the contribution of LTP-like mechanisms to object recognition memory maintenance. Infusion of ZIP into the perirhinal cortex of rats 24 h after the sample phase impaired performance in an object recognition but not an object location task, in contrast infusion of ZIP into the hippocampus impaired performance in an object location but not an object recognition task. The impairment in object recognition by ZIP was prevented by administration of the peptide GluA23y, which blocks the endocytosis of GluA2 containing AMPA receptors. Finally, performance in a perceptual oddity task, which requires perirhinal cortex function, was not disrupted by ZIP. Together these results demonstrate the importance of LTP-like mechanisms to the maintenance of object recognition memory in the perirhinal cortex.

How musical rhythm training improves short-term memory for faces

Playing a musical instrument engages numerous cognitive abilities, including sensory perception, selective attention, and short-term memory. Mounting evidence indicates that engaging these cognitive functions during musical training will improve performance of these same functions. Yet, it remains unclear the extent these benefits may extend to nonmusical tasks, and what neural mechanisms may enable such transfer. Here, we conducted a preregistered randomized clinical trial where nonmusicians underwent 8 wk of either digital musical rhythm training or word search as control. Only musical rhythm training placed demands on short-term memory, as well as demands on visual perception and selective attention, which are known to facilitate short-term memory. As hypothesized, only the rhythm training group exhibited improved short-term memory on a face recognition task, thereby providing important evidence that musical rhythm training can benefit performance on a nonmusical task. Analysis of electroencephalography data showed that neural activity associated with sensory processing and selective attention were unchanged by training. Rather, rhythm training facilitated neural activity associated with short-term memory encoding, as indexed by an increased P3 of the event-related potential to face stimuli. Moreover, short-term memory maintenance was enhanced, as evidenced by increased two-class (face/scene) decoding accuracy. Activity from both the encoding and maintenance periods each highlight the right superior parietal lobule (SPL) as a source for training-related changes. Together, these results suggest musical rhythm training may improve memory for faces by facilitating activity within the SPL to promote how memories are encoded and maintained, which can be used in a domain-general manner to enhance performance on a nonmusical task.

Dynamic auditory contributions to error detection revealed in the discrimination of Same and Different syllable pairs

During speech production auditory and motor regions within the sensorimotor dorsal stream operate in concert to facilitate online error detection. As the dorsal stream also is known to activate in speech perception, the purpose of the current study was to probe the role of auditory regions in error detection during auditory discrimination tasks as stimuli are encoded and maintained in working memory. A priori assumptions are that sensory mismatch (i.e., error) occurs during the discrimination of Different (mismatched) but not Same (matched) syllable pairs. Independent component analysis was applied to raw EEG data recorded from 42 participants to identify bilateral auditory alpha rhythms, which were decomposed across time and frequency to reveal robust patterns of event related synchronization (ERS; inhibition) and desynchronization (ERD; processing) over the time course of discrimination events. Results were characterized by bilateral peri-stimulus alpha ERD transitioning to alpha ERS in the late trial epoch, with ERD interpreted as evidence of working memory encoding via Analysis by Synthesis and ERS considered evidence of speech-induced-suppression arising during covert articulatory rehearsal to facilitate working memory maintenance. The transition from ERD to ERS occurred later in the left hemisphere for Different trials than for Same trials, with ERD and ERS temporally overlapping during the early post-stimulus window. Results were interpreted to suggest that the sensory mismatch (i.e., error) arising from the comparison of the first and second syllable elicits further processing in the left hemisphere to support working memory encoding and maintenance. Results are consistent with auditory contributions to error detection during both encoding and maintenance stages of working memory, with encoding stage error detection associated with stimulus concordance and maintenance stage error detection associated with task-specific retention demands.

The enigma of memory T cells in viral infections (including SARS-CoV-2)

Viral infections and vaccinations produce immune responses mostly through B cells (plasmocytes/ antibodies) and effector T cells (helper and cytotoxic). After removing the antigen, 90-95% of the effector cells disappear, but the remaining ones turn into T cells with long memory. The maintenance of cellular memory, the mode of information storage and the lifespan of T cells are insufficiently known. After measles, resident T cells in the plasma will offer protection only against the measles virus, generating a long period of immunodepression (immune amnesia).After the flu, memory T cells generate immune protection for 1-2 years for secretory IgA and longer for serum IgG. In SARS-CoV-2 infection, memory T cells (B and T) respond quickly to reinfection for 8-10 months. In conditions of intense stimulation in SARS-CoV-2, SARSCoV, MARS infection, marked leukopenia occurs with lymphopenia generating immunodepression and high mortality, disorders similar to septic shock. An important role in these disorders is played by the host's genetic structure and epigenome.

Brain correlates of action word memory revealed by fMRI.

Understanding language semantically related to actions activates the motor cortex. This activation is sensitive to semantic information such as the body part used to perform the action (e.g. arm-/leg-related action words). Additionally, motor movements of the hands/feet can have a causal effect on memory maintenance of action words, suggesting that the involvement of motor systems extends to working memory. This study examined brain correlates of verbal memory load for action-related words using event-related fMRI. Seventeen participants saw either four identical or four different words from the same category (arm-/leg-related action words) then performed a nonmatching-to-sample task. Results show that verbal memory maintenance in the high-load condition produced greater activation in left premotor and supplementary motor cortex, along with posterior-parietal areas, indicating that verbal memory circuits for action-related words include the cortical action system. Somatotopic memory load effects of arm- and leg-related words were observed, but only at more anterior cortical regions than was found in earlier studies employing passive reading tasks. These findings support a neurocomputational model of distributed action-perception circuits (APCs), according to which language understanding is manifest as full ignition of APCs, whereas working memory is realized as reverberant activity receding to multimodal prefrontal and lateral temporal areas.

Detection of Polyfunctional T Cells in Children Vaccinated with Japanese Encephalitis Vaccine via the Flow Cytometry Technique.

T cell-mediated immunity plays an important role in controlling flavivirus infection, either after vaccination or after natural infection. The "quality" of a T cell needs to be assessed by function, and higher function is associated with more powerful immune protection. T cells that can simultaneously produce two or more cytokines or chemokines at the single-cell level are called polyfunctional T cells (TPFs), which mediate immune responses through a variety of molecular mechanisms to express degranulation markers (CD107a) and secrete interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, or macrophage inflammatory protein (MIP)-1α. There is increasing evidence that TPFs are closely related to the maintenance of long-term immune memory and protection and that their increased proportion is an important marker of protective immunity and is important in the effective control of viral infection and reactivation. This evaluation applies not only to specific immune responses but also to the assessment of cross-reactive immune responses. Here, taking the Japanese encephalitis virus (JEV) as an example, the detection method and flow cytometry color scheme of JEV-specific TPFs produced by peripheral blood mononuclear cells of children vaccinated against Japanese encephalitis were tested to provide a reference for similar studies.

Sensorimotor and Frontoparietal Network Connectivity Are Associated With Subsequent Maintenance of Gait Speed and Episodic Memory in Older Adults.

Slow gait is predictive of functional impairments in older adults, while concomitant slow gait and cognitive complaints are associated with a greater risk for cognitive decline and dementia. However, functional neural correlates for gait speed maintenance are unclear. As the sensorimotor network (SMN) and frontoparietal network (FPN) are integral components of these functions, this study investigated differences in SMN and FPN in older adults with/without gait speed decline over 24 months; and whether these networks were associated with the maintenance of cognitive function. We included 42 community-dwelling older adults aged >70 years from the MOBILIZE Boston Study. Resting-state fMRI was performed at the study baseline. Participant characteristics, gait speed, Mini-Mental State Examination, and Hopkins Verbal Learning Test (HVLT) were assessed at baseline and at 24-month follow-up. Decliners were identified as individuals with >0.05 meters/second decline in gait speed from baseline to 24 months. Of the 26 decliners and 16 maintainers, decliners exhibited a significant decline in delayed-recall performance on the HVLT over 24 months. Controlling for baseline age and multiple comparisons, contrary to initial hypothesis, maintainers exhibited lower baseline primary motor and premotor connectivity (p = .01) within the SMN, and greater baseline ventral visual-supramarginal gyrus connectivity within the FPN (p = .02) compared to decliners. Lower primary motor-premotor connectivity was correlated with maintenance of delayed-recall performance on the HVLT (p = .04). These findings demonstrated a potential compensatory mechanism involved in the link between the decline in gait speed and episodic memory, whereby baseline connectivity of the SMN and FPN may underlie subsequent maintenance of gait speed and cognitive function in old age.

Spike-specific T-cell responses in patients with COVID-19 successfully treated with neutralizing monoclonal antibodies against SARS-CoV-2

ObjectivesNeutralizing monoclonal antibodies (moAbs) improves clinical outcomes in patients with COVID-19 when administered during the initial days of infection. The action of moAbs may impair the generation or maintenance of effective immune memory, similar to that demonstrated in other viral diseases. We aimed to evaluate short-term memory T-cell responses in patients effectively treated with bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab (SOT). MethodsSpike (S)-specific T-cell responses were analyzed in 23 patients with COVID-19 (vaccinated or unvaccinated) before and after a median of 50 (range: 28-93) days from moAb treatment, compared with 11 vaccinated healthy controls. T-cell responses were measured by interferon-γ-enzyme-linked immunospot and flow cytometric activation-induced marker assay. ResultsNo statistically significant difference in S-specific T-cell responses was observed between patients treated with moAb and vaccinated healthy controls. Bamlanivimab/etesevimab and casirivimab/imdevimab groups showed significant increases in cellular responses in paired baseline/postrecovery series, as well as vaccinated patients receiving SOT. In contrast, unvaccinated patients prescribed SOT presented no statistically significant increases in T-cell-responses, suggesting diverse impacts of different moAbs on the evolution of S-specific T-cell responses in vaccinated and unvaccinated patients. ConclusionThe moAbs did not hinder short-term memory S-specific T-cell responses in the overall group of patients; however, differences among moAbs must be further investigated both in vaccinated and unvaccinated individuals.

Scientific policy session: European GrantAntigen-delivery through invariant chain boosts CD8 and CD4 T cell immunity

Eradication of tumors by the immune system relies on the efficient activation of a T-cell response. For many years, the main focus of cancer immunotherapy has been on cytotoxic CD8 T-cell. However, stimulation of CD4 helper T cells is critical for the promotion and maintenance of immune memory, thus a good vaccine should evoke a two-dimensional T-cell response. The invariant chain (Ii) is required for the MHC class II heterodimer to be correctly guided through the cell, loaded with peptide, and expressed on the surface of antigen presenting cells (APC). We previously showed that by replacing the Ii CLIP peptide by an MHC-I cancer peptide, we could efficiently load MHC-I. This prompted us to test whether longer cancer peptides could be loaded on both MHC classes and whether such peptides could be accommodated in the CLIP region of Ii. We here present data showing that expanding the CLIP replacement size leads to T-cell activation. We demonstrate by using long peptides that APCs can present peptides from the same Ii molecule on both MHC-I and -II. Finally, we verified that Ii-expressing dendritic cells could prime CD4+ and CD8+ T cells from a naïve population. Taken together our study demonstrates that CLIP peptide replaced Ii constructs fulfill some of the major requirements for an efficient vector for cancer vaccination.

Homozygous knockout of eEF2K alleviates cognitive deficits in APP/PS1 Alzheimer's disease model mice independent of brain amyloid β pathology.

Maintenance of memory and synaptic plasticity depends on de novo protein synthesis, and accumulating evidence implicates a role of dysregulated mRNA translation in cognitive impairments associated with Alzheimer’s disease (AD). Accumulating evidence demonstrates hyper-phosphorylation of translation factor eukaryotic elongation factor 2 (eEF2) in the hippocampi of human AD patients as well as transgenic AD model mice. Phosphorylation of eEF2 (at the Thr 56 site) by its only known kinase, eEF2K, leads to inhibition of general protein synthesis. A recent study suggests that amyloid β (Aβ)-induced neurotoxicity could be associated with an interaction between eEF2 phosphorylation and the transcription factor nuclear erythroid 2-related factor (NRF2)-mediated antioxidant response. In this brief communication, we report that global homozygous knockout of the eEF2K gene alleviates deficits of long-term recognition and spatial learning in a mouse model of AD (APP/PS1). Moreover, eEF2K knockout does not alter brain Aβ pathology in APP/PS1 mice. The hippocampal NRF2 antioxidant response in the APP/PS1 mice, measured by expression levels of nicotinamide adenine dinucleotide plus hydrogen (NADPH) quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1), is ameliorated by suppression of eEF2K signaling. Together, the findings may contribute to our understanding of the molecular mechanisms underlying AD pathogenesis, indicating that suppression of eEF2K activity could be a beneficial therapeutic option for this devastating neurodegenerative disease.

Circadian photoreceptors are required for light-dependent maintenance of long-term memory in Drosophila

In the fruit fly Drosophila melanogaster, environmental light is required for maintaining long-term memory (LTM). Furthermore, the Pigment dispersing factor (Pdf), which is a circadian neuropeptide, and the neuronal activity of Pdf neurons are essential for light-dependent maintenance of courtship LTM. Since Pdf neurons can sense light directly via circadian photoreceptors [Rhodopsin 7 (Rh7) and Cryptochrome (Cry)], it is possible that Rh7 and Cry in Pdf neurons are involved in the maintenance of LTM. In this study, using a courtship conditioning assay, we demonstrated that circadian photoreceptors in Pdf neurons are required for maintaining courtship LTM.

The Transcription Factor Zfp335 Promotes Differentiation and Persistence of Memory CD8+ T Cells by Regulating TCF-1.

Memory CD8+ T cells play an essential role in providing effective and lifelong protection against pathogens. Comprehensive transcriptional and epigenetic networks are involved in modulating memory T cell development, but the molecular regulations of CD8+ memory T cell formation and long-term persistence remain largely unknown. In this study, we show that zinc finger protein 335 (Zfp335) is indispensable for CD8+ T cell memory establishment and maintenance during acute infections. Mice with Zfp335 deletion in CD8+ T cells exhibit a significant reduction of memory T cells and memory precursor cells in the contraction phase. Zfp335 deficiency in CD8+ T cells resulted in decreased expression of memory featured genes Eomes and IL-2Rβ, leading to a loss of memory identity and an increase of apoptosis in response to IL-7 and IL-15. Mechanistically, Zfp335 directly binds to and regulates TCF-1, known to be critical for memory T cell development. Importantly, overexpression TCF-1 could rescue the defects in the survival of both CD8+ memory precursors and memory T cells caused by Zfp335 deficiency. Collectively, our findings reveal that Zfp335 serves as a novel transcriptional factor upstream of TCF-1 in regulating CD8+ T cell memory.

The importance of ocular artifact removal in single-trial ERP analysis: The case of the N250 in face learning

ObjectiveSingle-trial event-related potentials (ERPs) offer fine-grained information about the trajectories of the neurocognitive processes but are highly sensitive to any artifacts in the EEG signal. The primary aim of this study was to assess the impact of ocular artifact removal on the single-trial N250 ERP analysis of face learning in individual participants. MethodsWe present a detailed description of our research-grade EEG hardware setup and a highly reproducible code (https://osf.io/aqhmn/) for generating time series of single-trial N250 ERP amplitudes and precise identification of a changepoint between face memory trace acquisition and maintenance. Ocular artifacts were removed using a new semi-automatic approach with only one hyperparameter based on the correlation between EEG components from independent component analysis (ICA) and the EOG signal. ResultsResults from the simulation study showed that our ocular artifact filtration decreased the average RMSE by half and achieved the highest increase of SNR among all the compared methods. It decreased standard deviations and improved the fit of the broken-line regression models for all participants by 25% ± 17% (min. 2%, max. 63%). Conclusions and significanceOcular artifact filtration had a substantial positive impact on the regression modeling of single-trial ERP amplitudes. Lack of ocular artifact removal can drastically distort the conclusions about the face learning process from single-trial N250 ERP experiments for individual participants. The changepoint locations changed for 13 out of 15 participants. This is the first published analysis of time series of single-trial N250 ERP amplitudes in face learning.

A glucose-target of rapamycin signaling axis integrates environmental history of heat stress through maintenance of transcription-associated epigenetic memory in Arabidopsis.

In nature, plants cope with adversity and have established strategies that recall past episodes and enable them to better cope with stress recurrences by establishing a 'stress memory'. Emerging evidence suggests that glucose (Glc) and target of rapamycin (TOR), central regulators of plant growth, have remarkable functions in stress adaptation. However, whether TOR modulates a stress memory response is so far unknown. Global transcriptome profiling identified that Glc, through TOR, regulates the expression of numerous genes involved in thermomemory. Priming of TOR overexpressors with mild heat showed better stress endurance, whereas TOR RNAi showed reduced thermomemory. This thermomemory is linked with histone methylation at specific sites of heat stress (HS) genes. TOR promotes long-term accumulation of H3K4me3 on thermomemory-associated gene promoters, even when transcription of those genes reverts to their basal level. Our results suggest that ARABIDOPSIS TRITHORAX 1 (ATX1), an H3K4 methyltransferase already shown to regulate H3K4me3 levels at the promoters of HS recovery genes, is a direct target of TOR signaling. The TOR-activating E2Fa binds to the promoter of ATX1 and regulates its expression, which ultimately regulates thermomemory. Collectively, our findings reveal a mechanistic framework in which Glc-TOR signaling determines the integration of stress and energy signaling to regulate thermomemory.

Cognitive and perceptual impairments in schizophrenia extend to other psychotic disorders but not schizotypy

Well characterised cognitive and perceptual impairments in schizophrenia may not be diagnostically specific with some studies suggesting no significant differences between psychotic disorders. This transdiagnostic ambiguity is paralleled in the boundary distinctions between psychotic disorders and the sub-threshold symptomatology of schizotypy. The current study used the CNTRACS test battery to explore if performance deficits in visual integration, relational memory and goal maintenance were specific to schizophrenia or extend to other psychotic disorders; and if task performance varied between individuals with schizophrenia and schizotypy in healthy adults. The sample consisted of healthy controls, and patients who met DSM-IV criteria for schizophrenia, other psychotic disorders and non-psychotic disorders who were tested in person; and an online sample of self-assessed healthy adults. No significant differences were found in performance between patients with schizophrenia and other psychotic disorders in contrast to non-psychotic disorders and healthy controls. The high schizotypy group performed better on the tasks compared to the other psychoses and schizophrenia groups. There were no differences in the healthy control group between individuals with high versus low schizotypy or between in-person and online task performance. These findings support the notion that cognitive and perceptual impairments in schizophrenia extend to other psychotic disorders but are discontinuous with schizotypy. This study provides insights into similarities between schizophrenia and other psychotic disorders with regards to the potential neural substrates underpinning these functions and supports the use of online tools for assessing domains of cognition and perception.

Intermittent Fasting Improves Memory, Reduces Anxiety and Enhances Neurotransmitter Levels In Zebrafish (Danio Rerio)

The zebrafish is an excellent model for social, behavioural and neuroscience studies. The brain controls food intake, energy expenditure, insulin secretion, hepatic glucose production, and glucose fatty acid metabolism in adipose tissue and skeletal muscle. Caloric restriction is thought to be the main reason for disease regulation. The sensory system strengthens by altering the union of neurotrophins and synapses. The experimental groups studied in this research included control, uncontrolled diet-(overfed), 12hrs, 24hrs, 48hrs intermittent fasting, respectively. The study groups were subjected to a T-maze test to examine zebrafish memory and learning changes. The novel tank test (NTT) and light and dark (LDT) tests investigated stress-like behaviour. The levels of dopamine, serotonin, epinephrine, and nor-epinephrine were measured using a spectrofluorimetric method. We found behaviour and enhanced neurotransmitter levels in the groups that were subjected to intermittent fasting than the overfed and control groups which may be due to the hippocampus derived neurotrophic factor that in areas memory power and reduce anxiety from this experiment it is evident that intermittent fasting could bring a positive outcome in memory maintenance by lowering the anxiety and thereby keeping a check in neurotransmitter levels.

Priming seeds for the future: Plant immune memory and application in crop protection

Plants have evolved adaptive strategies to cope with pathogen infections that seriously threaten plant viability and crop productivity. Upon the perception of invading pathogens, the plant immune system is primed, establishing an immune memory that allows primed plants to respond more efficiently to the upcoming pathogen attacks. Physiological, transcriptional, metabolic, and epigenetic changes are induced during defense priming, which is essential to the establishment and maintenance of plant immune memory. As an environmental-friendly technique in crop protection, seed priming could effectively induce plant immune memory. In this review, we highlighted the recent advances in the establishment and maintenance mechanisms of plant defense priming and the immune memory associated, and discussed strategies and challenges in exploiting seed priming on crops to enhance disease resistance.

Impact of Perineuronal Net Removal in the Rat Medial Prefrontal Cortex on Parvalbumin Interneurons After Reinstatement of Cocaine Conditioned Place Preference.

Parvalbumin (PV)-positive cells are GABAergic fast-spiking interneurons that modulate the activity of pyramidal neurons in the medial prefrontal cortex (mPFC) and their output to brain areas associated with learning and memory. The majority of PV cells within the mPFC are surrounded by a specialized extracellular matrix structure called the perineuronal net (PNN). We have shown that removal of PNNs with the enzyme chondroitinase-ABC (Ch-ABC) in the mPFC prevents the consolidation and reconsolidation of cocaine-associated conditioned place preference (CPP) memories. Here we examined the extent to which retrieval of a CPP memory during cocaine-primed reinstatement altered the levels and function of PV neurons and their surrounding PNNs during the reconsolidation period. We further determined the extent to which PNN removal prior to reinstatement altered PV intensity levels and PV cell function. Male Sprague-Dawley rats were trained for cocaine-induced conditioned place preference (CPP) followed by extinction training, microinjection of Ch-ABC in the prelimbic PFC, and cocaine-induced reinstatement. Rats were sacrificed immediately prior to reinstatement or at 2 h, 6 h, or 48 h after reinstatement for immunohistochemistry or 2 h later for electrophysiology. Our findings indicate that PNN removal only partially diminished reinstatement. Cocaine-primed reinstatement produced only minor changes in PNN or PV intensity in vehicle controls. However, after PNN removal, the intensity of remaining PNN-surrounded PV cells was decreased at all times except at 2 h post-reinstatement, at which time cocaine increased PV intensity. Consistent with this, in vehicle controls, PV neurons naturally devoid of PNNs showed a similar pattern to Ch-ABC-treated rats prior to and after cocaine reinstatement, suggesting a protective effect of PNNs on cocaine-induced changes in PV intensity. Using whole-cell patch-clamp, cocaine-primed reinstatement in Ch-ABC-treated rats decreased the number of elicited action potentials but increased excitatory synaptic transmission, which may have been compensatory. These findings suggest that without PNNs, cocaine-induced reinstatement produces rapid changes in PV intensity and PV cell excitability, which may in turn regulate output of the mPFC post-memory retrieval and diminish the maintenance of cocaine memory during reconsolidation.