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

Science ◽  
2019 ◽  
Vol 365 (6455) ◽  
pp. 821-825 ◽  
Author(s):  
Walter G. Gonzalez ◽  
Hanwen Zhang ◽  
Anna Harutyunyan ◽  
Carlos Lois
Keyword(s):  
Neuronal Activity ◽  
Neuronal Responses ◽  
Synchronous Activity ◽  
Mouse Hippocampus

How do neurons encode long-term memories? Bilateral imaging of neuronal activity in the mouse hippocampus reveals that, from one day to the next, ~40% of neurons change their responsiveness to cues, but thereafter only 1% of cells change per day. Despite these changes, neuronal responses are resilient to a lack of exposure to a previously completed task or to hippocampus lesions. Unlike individual neurons, the responses of which change after a few days, groups of neurons with inter- and intrahemispheric synchronous activity show stable responses for several weeks. The likelihood that a neuron maintains its responsiveness across days is proportional to the number of neurons with which its activity is synchronous. Information stored in individual neurons is relatively labile, but it can be reliably stored in networks of synchronously active neurons.

scholarly journals Aη-α and Aη-β peptides impair LTP ex vivo within the low nanomolar range and impact neuronal activity in vivo

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Maria Mensch ◽  
Jade Dunot ◽  
Sandy M. Yishan ◽  
Samuel S. Harris ◽  
Aline Blistein ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Ex Vivo ◽  
Long Term Potentiation ◽  
Network Activity ◽  
Strongly Correlated ◽  
App Processing ◽  
Term Potentiation ◽  
Hippocampal Network

Abstract Background Amyloid precursor protein (APP) processing is central to Alzheimer’s disease (AD) etiology. As early cognitive alterations in AD are strongly correlated to abnormal information processing due to increasing synaptic impairment, it is crucial to characterize how peptides generated through APP cleavage modulate synapse function. We previously described a novel APP processing pathway producing η-secretase-derived peptides (Aη) and revealed that Aη–α, the longest form of Aη produced by η-secretase and α-secretase cleavage, impaired hippocampal long-term potentiation (LTP) ex vivo and neuronal activity in vivo. Methods With the intention of going beyond this initial observation, we performed a comprehensive analysis to further characterize the effects of both Aη-α and the shorter Aη-β peptide on hippocampus function using ex vivo field electrophysiology, in vivo multiphoton calcium imaging, and in vivo electrophysiology. Results We demonstrate that both synthetic peptides acutely impair LTP at low nanomolar concentrations ex vivo and reveal the N-terminus to be a primary site of activity. We further show that Aη-β, like Aη–α, inhibits neuronal activity in vivo and provide confirmation of LTP impairment by Aη–α in vivo. Conclusions These results provide novel insights into the functional role of the recently discovered η-secretase-derived products and suggest that Aη peptides represent important, pathophysiologically relevant, modulators of hippocampal network activity, with profound implications for APP-targeting therapeutic strategies in AD.

scholarly journals The Kynurenic Acid Analog SZR72 Enhances Neuronal Activity after Asphyxia but Is Not Neuroprotective in a Translational Model of Neonatal Hypoxic Ischemic Encephalopathy

2021 ◽  
Vol 22 (9) ◽  
pp. 4822
Author(s):  
Viktória Kovács ◽  
Gábor Remzső ◽  
Tímea Körmöczi ◽  
Róbert Berkecz ◽  
Valéria Tóth-Szűki ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Kynurenic Acid ◽  
Neuronal Damage ◽  
Brain Regions ◽  
Hypoxic Ischemic Encephalopathy ◽  
Hippocampal Field ◽  
Power Spectral ◽  
Density Values ◽  
Ischemic Encephalopathy

Hypoxic–ischemic encephalopathy (HIE) remains to be a major cause of long-term neurodevelopmental deficits in term neonates. Hypothermia offers partial neuroprotection warranting research for additional therapies. Kynurenic acid (KYNA), an endogenous product of tryptophan metabolism, was previously shown to be beneficial in rat HIE models. We sought to determine if the KYNA analog SZR72 would afford neuroprotection in piglets. After severe asphyxia (pHa = 6.83 ± 0.02, ΔBE = −17.6 ± 1.2 mmol/L, mean ± SEM), anesthetized piglets were assigned to vehicle-treated (VEH), SZR72-treated (SZR72), or hypothermia-treated (HT) groups (n = 6, 6, 6; Tcore = 38.5, 38.5, 33.5 °C, respectively). Compared to VEH, serum KYNA levels were elevated, recovery of EEG was faster, and EEG power spectral density values were higher at 24 h in the SZR72 group. However, instantaneous entropy indicating EEG signal complexity, depression of the visual evoked potential (VEP), and the significant neuronal damage observed in the neocortex, the putamen, and the CA1 hippocampal field were similar in these groups. In the caudate nucleus and the CA3 hippocampal field, neuronal damage was even more severe in the SZR72 group. The HT group showed the best preservation of EEG complexity, VEP, and neuronal integrity in all examined brain regions. In summary, SZR72 appears to enhance neuronal activity after asphyxia but does not ameliorate early neuronal damage in this HIE model.

scholarly journals Long-Lasting Hyperexcitability Induced by Depolarization in the Absence of Detectable Ca2+ Signals

2009 ◽  
Vol 101 (3) ◽  
pp. 1351-1360 ◽  
Author(s):  
Kumud K. Kunjilwar ◽  
Harvey M. Fishman ◽  
Dario J. Englot ◽  
Roger G. O'Neil ◽  
Edgar T. Walters
Keyword(s):  
Protein Synthesis ◽  
Neuronal Injury ◽  
Adaptive Responses ◽  
Neuronal Responses ◽  
Local Protein Synthesis ◽  
Neuronal Viability ◽  
Nerve Ganglion ◽  
Dissociated Cell Culture ◽  
Activity Dependent

Learning and memory depend on neuronal alterations induced by electrical activity. Most examples of activity-dependent plasticity, as well as adaptive responses to neuronal injury, have been linked explicitly or implicitly to induction by Ca2+ signals produced by depolarization. Indeed, transient Ca2+ signals are commonly assumed to be the only effective transducers of depolarization into adaptive neuronal responses. Nevertheless, Ca2+-independent depolarization-induced signals might also trigger plastic changes. Establishing the existence of such signals is a challenge because procedures that eliminate Ca2+ transients also impair neuronal viability and tolerance to cellular stress. We have taken advantage of nociceptive sensory neurons in the marine snail Aplysia, which exhibit unusual tolerance to extreme reduction of extracellular and intracellular free Ca2+ levels. The axons of these neurons exhibit a depolarization-induced memory-like hyperexcitability that lasts a day or longer and depends on local protein synthesis for induction. Here we show that transient localized depolarization of these axons in an excised nerve–ganglion preparation or in dissociated cell culture can induce short- and intermediate-term axonal hyperexcitability as well as long-term protein synthesis–dependent hyperexcitability under conditions in which Ca2+ entry is prevented (by bathing in nominally Ca2+ -free solutions containing EGTA) and detectable Ca2+ transients are eliminated (by adding BAPTA-AM). Disruption of Ca2+ release from intracellular stores by pretreatment with thapsigargin also failed to affect induction of axonal hyperexcitability. These findings suggest that unrecognized Ca2+-independent signals exist that can transduce intense depolarization into adaptive cellular responses during neuronal injury, prolonged high-frequency activity, or other sustained depolarizing events.

scholarly journals Neuronal Responses to Short Wavelength Light Deficiency in the Rat Subcortical Visual System

2021 ◽  
Vol 14 ◽  
Author(s):  
Patrycja Orlowska-Feuer ◽  
Magdalena Kinga Smyk ◽  
Anna Alwani ◽  
Marian Henryk Lewandowski
Keyword(s):  
Neuronal Activity ◽  
Short Wavelength ◽  
Uv Light ◽  
Spectral Composition ◽  
Dorsal Lateral Geniculate Nucleus ◽  
Neuronal Responses ◽  
Polychromatic Light ◽  
Electrophysiological Recordings ◽  
Pretectal Nucleus ◽  
Short Wavelength Light

The amount and spectral composition of light changes considerably during the day, with dawn and dusk being the most crucial moments when light is within the mesopic range and short wavelength enriched. It was recently shown that animals use both cues to adjust their internal circadian clock, thereby their behavior and physiology, with the solar cycle. The role of blue light in circadian processes and neuronal responses is well established, however, an unanswered question remains: how do changes in the spectral composition of light (short wavelengths blocking) influence neuronal activity? In this study we addressed this question by performing electrophysiological recordings in image (dorsal lateral geniculate nucleus; dLGN) and non-image (the olivary pretectal nucleus; OPN, the suprachiasmatic nucleus; SCN) visual structures to determine neuronal responses to spectrally varied light stimuli. We found that removing short-wavelength from the polychromatic light (cut off at 525 nm) attenuates the most transient ON and sustained cells in the dLGN and OPN, respectively. Moreover, we compared the ability of different types of sustained OPN neurons (either changing or not their response profile to filtered polychromatic light) to irradiance coding, and show that both groups achieve it with equal efficacy. On the other hand, even very dim monochromatic UV light (360 nm; log 9.95 photons/cm2/s) evokes neuronal responses in the dLGN and SCN. To our knowledge, this is the first electrophysiological experiment supporting previous behavioral findings showing visual and circadian functions disruptions under short wavelength blocking environment. The current results confirm that neuronal activity in response to polychromatic light in retinorecipient structures is affected by removing short wavelengths, however, with type and structure – specific action. Moreover, they show that rats are sensitive to even very dim UV light.

scholarly journals Pre-stimulus phase and amplitude regulation of phase-locked responses are maximized in the critical state

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Arthur-Ervin Avramiea ◽  
Richard Hardstone ◽  
Jan-Matthis Lueckmann ◽  
Jan Bím ◽  
Huibert D Mansvelder ◽  
...  
Keyword(s):  
Computational Model ◽  
Critical State ◽  
Global Dynamics ◽  
Critical Dynamics ◽  
Neuronal Responses ◽  
Scale Free ◽  
Stimulus Response ◽  
Functional States ◽  
The Brain

Understanding why identical stimuli give differing neuronal responses and percepts is a central challenge in research on attention and consciousness. Ongoing oscillations reflect functional states that bias processing of incoming signals through amplitude and phase. It is not known, however, whether the effect of phase or amplitude on stimulus processing depends on the long-term global dynamics of the networks generating the oscillations. Here, we show, using a computational model, that the ability of networks to regulate stimulus response based on pre-stimulus activity requires near-critical dynamics—a dynamical state that emerges from networks with balanced excitation and inhibition, and that is characterized by scale-free fluctuations. We also find that networks exhibiting critical oscillations produce differing responses to the largest range of stimulus intensities. Thus, the brain may bring its dynamics close to the critical state whenever such network versatility is required.

Construction and optimization of herpes simplex virus vectors for central nervous system gene delivery based on CRISPR/Cas9-mediated genome editing

2021 ◽  
Vol 21 ◽  
Author(s):  
Xinwei Huang ◽  
Xiuqing Li ◽  
Lijuan Yang ◽  
Pengfei Wang ◽  
Jingyuan Yan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Transgene Expression ◽  
Mouse Hippocampus ◽  
Simplex Virus ◽  
Hsv 1

Aims: We aim to define parameters affecting the safety and long-term transgene expression of attenuated HSV-1 vectors and optimize the expression cassettes to achieve robust and sustained expression in CNS. Background: Engineered, attenuated Herpes simplex virus (HSV) vectors are promising vehicles for gene delivery to the peripheral and central nervous systems. The virus latent promoter (LAP) is commonly used to drive exogenous gene expression; however, parameters affecting the safety and long-term transgene expression of attenuated HSV-1 vectors have not been fully understood. Objective: This study aimed to construct attenuated HSV-1 vectors using the CRISPR-Cas9 system and examine the influence of transgene cassette construction and insertion site on transgene expression and vector safety. Method: In this study, we used a CRISPR-Cas9 system to accurately and efficiently edit attenuated HSV-1 strain 1716, and constructed two series of recombinant virus LMR and LMRx with different sets of gene cassettes insertion in Exon1(LAP2) and 2.0 kb intron downstream of LAP, respectively. The transgene expression and viral gene transcriptional kinetics were compared in in-vitro cell lines. The reporter gene expression and safety profiles of each vector were further evaluated in the mouse hippocampus gene transduction model. Result: The in-vitro cell line analysis indicated that the insertion of a gene expression cassette would disrupt virus gene transcription. Mouse hippocampus transducing analysis suggested that complete expression cassette insertion at 2.0 kb intron could achieve robust and longtime gene expression than the other constructs. Recombinants with gene expression cassettes lacked Poly (A), which induced significant neuronal inflammation due to persistent viral antigen expression and microglia activation. Conclusion: Our results indicated that the integrity of LAT transcripts was not necessary for the establishment of long-term latent expression. Exogenous strong promoters (like cBh promoter) could remain active during latency when placed in Exon1 or 2.0 Kb Intron of LAT locus, although their transcriptional activity declined with time. Consistent with previous research, the foreign gene expression would last much longer when the gene cassette was located downstream of Exon1, which suggested a role of LAP2 in maintaining promoter activity during latency. Besides, over-transcription of the downstream part of LAT may induce continuous activation of the attenuated vectors, suggesting an important role of LAT in maintaining viral reactivation potential.

scholarly journals Confidence-Related Decision Making

2010 ◽  
Vol 104 (1) ◽  
pp. 539-547 ◽  
Author(s):  
Andrea Insabato ◽  
Mario Pannunzi ◽  
Edmund T. Rolls ◽  
Gustavo Deco
Keyword(s):  
Decision Making ◽  
Cognitive Functioning ◽  
Neuronal Activity ◽  
Emergent Property ◽  
Neuronal Responses ◽  
Attractor Network ◽  
Firing Rates ◽  
Integrate And Fire ◽  
The Brain ◽  
High Firing

Neurons have been recorded that reflect in their firing rates the confidence in a decision. Here we show how this could arise as an emergent property in an integrate-and-fire attractor network model of decision making. The attractor network has populations of neurons that respond to each of the possible choices, each biased by the evidence for that choice, and there is competition between the attractor states until one population wins the competition and finishes with high firing that represents the decision. Noise resulting from the random spiking times of individual neurons makes the decision making probabilistic. We also show that a second attractor network can make decisions based on the confidence in the first decision. This system is supported by and accounts for neuronal responses recorded during decision making and makes predictions about the neuronal activity that will be found when a decision is made about whether to stay with a first decision or to abort the trial and start again. The research shows how monitoring can be performed in the brain and this has many implications for understanding cognitive functioning.

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