scholarly journals Persistence of neuronal representations through time and damage in the hippocampus

2019 ◽  
Author(s):  
Walter G. Gonzalez ◽  
Hanwen Zhang ◽  
Anna Harutyunyan ◽  
Carlos Lois

AbstractMemories can persist for decades but how they are stably encoded in individual and groups of neurons is not known. To investigate how a familiar environment is encoded in CA1 neurons over time we implanted bilateral microendoscopes in transgenic mice to image the activity of pyramidal neurons in the hippocampus over weeks. Most of the neurons (90 %) are active every day, however, the response of neurons to specific cues changes across days. Approximately 40 % of place and time cells lose fields between two days; however, on timescales longer than two days the neuronal pattern changes at a rate of 1 % for each additional day. Despite continuous changes, field responses are more resilient, with place/time cells recovering their fields after a 10-day period of no task or following CA1 damage. Recovery of these neuronal patterns is characterized by transient changes in firing fields which ultimately converge to the original representation. Unlike individual neurons, groups of neurons with inter and intrahemispheric synchronous activity form stable place and time fields across days. Neurons whose activity was synchronous with a large group of neurons were more likely to preserve their responses to place or time across multiple days. These results support the view that although task-relevant information stored in individual neurons is relatively labile, it can persist in networks of neurons with synchronized activity spanning both hemispheres.One Sentence SummaryNeuronal representations in networks of neurons with synchronized activity are stable over weeks, even after lack of training or following damage.


2021 ◽  
Author(s):  
Mustapha Abba ◽  
Chidozie Nduka ◽  
Seun Anjorin ◽  
Shukri Mohamed ◽  
Emmanuel Agogo ◽  
...  

BACKGROUND Due to scientific and technical advancements in the field, published hypertension research has developed during the last decade. Given the huge amount of scientific material published in this field, identifying the relevant information is difficult. We employed topic modelling, which is a strong approach for extracting useful information from enormous amounts of unstructured text. OBJECTIVE To utilize a machine learning algorithm to uncover hidden topics and subtopics from 100 years of peer-reviewed hypertension publications and identify temporal trends. METHODS The titles and abstracts of hypertension papers indexed in PubMed were examined. We used the Latent Dirichlet Allocation (LDA) model to select 20 primary subjects and then ran a trend analysis to see how popular they were over time. RESULTS We gathered 581,750 hypertension-related research articles from 1900 to 2018 and divided them into 20 categories. Preclinical, risk factors, complications, and therapy studies were the categories used to categorise the publications. We discovered themes that were becoming increasingly ‘hot,' becoming less ‘cold,' and being published seldom. Risk variables and major cardiovascular events subjects displayed very dynamic patterns over time (how? – briefly detail here). The majority of the articles (71.2%) had a negative valency, followed by positive (20.6%) and neutral valencies (8.2 percent). Between 1980 and 2000, negative sentiment articles fell somewhat, while positive and neutral sentiment articles climbed significantly. CONCLUSIONS This unique machine learning methodology provided fascinating insights on current hypertension research trends. This method allows researchers to discover study subjects and shifts in study focus, and in the end, it captures the broader picture of the primary concepts in current hypertension research articles. CLINICALTRIAL Not applicable



2000 ◽  
Vol 84 (5) ◽  
pp. 2398-2408 ◽  
Author(s):  
Nathan P. Staff ◽  
Hae-Yoon Jung ◽  
Tara Thiagarajan ◽  
Michael Yao ◽  
Nelson Spruston

Action potentials are the end product of synaptic integration, a process influenced by resting and active neuronal membrane properties. Diversity in these properties contributes to specialized mechanisms of synaptic integration and action potential firing, which are likely to be of functional significance within neural circuits. In the hippocampus, the majority of subicular pyramidal neurons fire high-frequency bursts of action potentials, whereas CA1 pyramidal neurons exhibit regular spiking behavior when subjected to direct somatic current injection. Using patch-clamp recordings from morphologically identified neurons in hippocampal slices, we analyzed and compared the resting and active membrane properties of pyramidal neurons in the subiculum and CA1 regions of the hippocampus. In response to direct somatic current injection, three subicular firing types were identified (regular spiking, weak bursting, and strong bursting), while all CA1 neurons were regular spiking. Within subiculum strong bursting neurons were found preferentially further away from the CA1 subregion. Input resistance ( R N), membrane time constant (τm), and depolarizing “sag” in response to hyperpolarizing current pulses were similar in all subicular neurons, while R N and τm were significantly larger in CA1 neurons. The first spike of all subicular neurons exhibited similar action potential properties; CA1 action potentials exhibited faster rising rates, greater amplitudes, and wider half-widths than subicular action potentials. Therefore both the resting and active properties of CA1 pyramidal neurons are distinct from those of subicular neurons, which form a related class of neurons, differing in their propensity to burst. We also found that both regular spiking subicular and CA1 neurons could be transformed into a burst firing mode by application of a low concentration of 4-aminopyridine, suggesting that in both hippocampal subfields, firing properties are regulated by a slowly inactivating, D-type potassium current. The ability of all subicular pyramidal neurons to burst strengthens the notion that they form a single neuronal class, sharing a burst generating mechanism that is stronger in some cells than others.



1986 ◽  
Vol 56 (2) ◽  
pp. 507-522 ◽  
Author(s):  
S. M. Thompson ◽  
D. A. Prince

Intracellular recordings were obtained from guinea pig hippocampal CA1 pyramidal neurons maintained in vitro. Focal applications of glutamate produced depolarizations followed by prolonged hyperpolarizations. The mechanisms underlying this postglutamate hyperpolarization (PGH) were investigated. PGH did not reverse polarity with hyperpolarization to potentials at or near the presumed K+ equilibrium potential. A transient increase in conductance was associated with the PGH; control values returned well before the termination of PGH. Application of Mn2+, an antagonist of voltage-dependent calcium conductance, blocked synaptic transmission and the afterhyperpolarization (AHP) that follows a directly evoked train of action potentials but did not diminish the PGH or the transient conductance increase. Intracellular application of the calcium chelator ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid blocked AHP but did not affect PGH. Reductions in temperature from 37 to 27-32 degrees C reduced the amplitude of PGH and prolonged its duration but increased the amplitude and duration of AHP. The transient conductance increase associated with PGH was unaffected. Application of strophanthidin, a specific antagonist of Na+-K+-ATPase, reversibly blocked PGH and led to large increases in the amplitude and duration of the AHP. It is concluded that PGH is produced by activation of the electrogenic sodium pump by glutamate-induced excitation. As such, PGH is a useful physiological assay of electrogenic sodium transport. In addition, maintenance of the Na+ gradient by the sodium pump is important for the buffering of Ca2+ influx.



2008 ◽  
Vol 22 (2) ◽  
pp. 199-222 ◽  
Author(s):  
Uday Chandra ◽  
Byung T. Ro

SYNOPSIS: This study examines the role of revenue in valuing firms beyond earnings and investigates whether this (1) is pervasive or limited to certain situations in which earnings may be less informative, (2) is sensitive to nonlinearity in the relation between returns and earnings, and (3) has changed over time. Our analysis indicates that revenue is useful both as a summary measure for valuation purposes and in conveying new information to the market, after controlling for earnings information. These results are not driven by technology firms, extreme earnings news or loss situations, or by model misspecification because of nonlinearities. The role of revenue in firm valuation is greater, and the role of earnings is smaller, in extreme earnings situations. We also find that revenue is more useful in summarizing the performance of technology firms and for profit observations. While the combined ability of revenue and earnings to summarize contemporaneous value-relevant information has remained stable over time, the new information conveyed by earnings has declined whereas the ability of revenue to incrementally convey new information has not diminished.



2020 ◽  
Vol 14 ◽  
Author(s):  
Pedro Mabil ◽  
Nayeli Huidobro ◽  
Oswaldo Torres-Ramirez ◽  
Jorge Flores-Hernandez ◽  
Amira Flores ◽  
...  


2020 ◽  
Vol 12 (529) ◽  
pp. eaay3069 ◽  
Author(s):  
Albert A. Davis ◽  
Casey E. Inman ◽  
Zachary M. Wargel ◽  
Umber Dube ◽  
Brittany M. Freeberg ◽  
...  

Apolipoprotein E (APOE) ε4 genotype is associated with increased risk of dementia in Parkinson’s disease (PD), but the mechanism is not clear, because patients often have a mixture of α-synuclein (αSyn), amyloid-β (Aβ), and tau pathologies. APOE ε4 exacerbates brain Aβ pathology, as well as tau pathology, but it is not clear whether APOE genotype independently regulates αSyn pathology. In this study, we generated A53T αSyn transgenic mice (A53T) on Apoe knockout (A53T/EKO) or human APOE knockin backgrounds (A53T/E2, E3, and E4). At 12 months of age, A53T/E4 mice accumulated higher amounts of brainstem detergent-insoluble phosphorylated αSyn compared to A53T/EKO and A53T/E3; detergent-insoluble αSyn in A53T/E2 mice was undetectable. By immunohistochemistry, A53T/E4 mice displayed a higher burden of phosphorylated αSyn and reactive gliosis compared to A53T/E2 mice. A53T/E2 mice exhibited increased survival and improved motor performance compared to other APOE genotypes. In a complementary model of αSyn spreading, striatal injection of αSyn preformed fibrils induced greater accumulation of αSyn pathology in the substantia nigra of A53T/E4 mice compared to A53T/E2 and A53T/EKO mice. In two separate cohorts of human patients with PD, APOE ε4/ε4 individuals showed the fastest rate of cognitive decline over time. Our results demonstrate that APOE genotype directly regulates αSyn pathology independent of its established effects on Aβ and tau, corroborate the finding that APOE ε4 exacerbates pathology, and suggest that APOE ε2 may protect against αSyn aggregation and neurodegeneration in synucleinopathies.



2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Zhi-Bin Liu ◽  
Chao Liu ◽  
Bin Zeng ◽  
Li-Ping Huang ◽  
Li-Hua Yao

Our previous study revealed that cordycepin features important neuroprotective effects against hypoxic insult by improvement of neuronal electrophysiological function. Modulation on voltage-gated sodium channel (VGSC) in CA1 neurons is the initial event during hypoxia/ischemia. However, no study comprehensively investigated cordycepin on VGSC. Hence, this study investigated modulation effects of cordycepin on VGSC not only in oxygen physiological conditions but also in acute oxygen deprivation injury conditions. Results revealed that cordycepin (80 μM) reduced the amplitude of VGSC currents (INa) (77.6% of control, p<0.01) within 1 min of drug exposure coupled with a negative shift in steady-state inactivation and prolonged recovery time course from inactivation. Additionally, this mild reduction on the peak of INa induced by the pretreatment with cordycepin can attenuate and delay the following hypoxia causing rapid dramatic decrease in INa with no additive change in the voltage dependence of inactivation. As modulation on VGSC in CA1 neurons represents the initial event during ischemia, we propose that suppression effect of cordycepin on VGSC is an important neuronal protective mechanism that may enhance neuronal tolerance to acute oxygen deprivation and delay hypoxia-induced neuronal injuries.



1992 ◽  
Vol 12 (3) ◽  
pp. 408-417 ◽  
Author(s):  
Takaaki Kirino ◽  
Hugh P. C. Robinson ◽  
Akiko Miwa ◽  
Akira Tamura ◽  
Nobufumi Kawai

Slice preparations were made from the hippocampus of gerbils after 5 min of ischemia by carotid artery occlusion and the membrane properties of pyramidal neurons were examined. A majority of CA1 neurons lost the capacity for long-term potentiation following tetanic stimulation of the input fibers. CA3 pyramidal neurons, in contrast, preserved responses similar to those in the normal gerbil. Following ischemia, CA1 pyramidal neurons showed increased spontaneous firing that was highly voltage dependent and was blocked by intracellular injection of the Ca2+ chelator, EGTA. Thirty-five percent of CA1 neurons showed an abnormal slow oscillation of the membrane potential after 24 h following ischemia. Intracellular injection of GTPγS or IP3 produced facilitation of the oscillations followed by irreversible depolarization. Our results indicate that ischemia-damaged CA1 neurons suffer from abnormal Ca2+ homeostasis, involving IP3-induced liberation of Ca2+ from internal stores.



2009 ◽  
Vol 30 (3) ◽  
pp. 555-565 ◽  
Author(s):  
Hui Ye ◽  
Shirin Jalini ◽  
Liang Zhang ◽  
Milton Charlton ◽  
Peter L Carlen

Two types of quantal spontaneous neurotransmitter release are present in the nervous system, namely action potential (AP)-dependent release and AP-independent release. Previous studies have identified and characterized AP-independent release during hypoxia and ischemia. However, the relative contribution of AP-dependent spontaneous release to the overall glutamate released during transient ischemia has not been quantified. Furthermore, the neuronal activity that mediates such release has not been identified. Using acute brain slices, we show that AP-dependent release constitutes approximately one-third of the overall glutamate-mediated excitatory postsynaptic potentials/currents (EPSPs/EPSCs) measured onto hippocampal CA1 pyramidal neurons. However, during transient (2 mins) in vitro hypoxia–hypoglycemia, large-amplitude, AP-dependent spontaneous release is significantly enhanced and contributes to 74% of the overall glutamatergic responses. This increased AP-dependent release is due to hyper-excitability in the presynaptic CA3 neurons, which is mediated by the activity of NMDA receptors. Spontaneous glutamate release during ischemia can lead to excitotoxicity and perturbation of neural network functions.



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