Structural network heterogeneities and network dynamics: a possible dynamical mechanism for hippocampal memory reactivation

The hippocampus has the capacity for reactivating recently acquired memories [1-3] and it is hypothesized that one of the functions of sleep reactivation is the facilitation of consolidation of novel memory traces [4-11]. The dynamic and network processes underlying such a reactivation remain, however, unknown. We show that such a reactivation characterized by local, self-sustained activity of a network region may be an inherent property of the recurrent excitatory-inhibitory network with a heterogeneous structure. The entry into the reactivation phase is mediated through a physiologically feasible regulation of global excitability and external input sources, while the reactivated component of the network is formed through induced network heterogeneities during learning. We show that structural changes needed for robust reactivation of a given network region are well within known physiological parameters [12,13].Comment: 16 pages, 5 figure

Radiation‐Induced Oral Mucositis Hamster Model Using a Linear Accelerator Enhances Clinical Relevance of Preclinical Studies for Treatment Strategy Investigation

Translational animal models for oral mucositis (OM) are necessary to simulate and assess the bioclinical effects and response in humans. These models should simulate high levels of radiation exposure that leads to oxidative stress and inflammatory‐initiated tissue changes. Hamster models have been extensively studied to observe pathological effects of radiation exposure and help in the development of effective treatments. To successfully evaluate the potential for treatment regimens with consistency and relevance, a radiation‐induced OM hamster model was developed using a clinical linear accelerator utilized by cancer patients daily. The dose exposure to the isolated, everted cheek pouch of a hamster, as well as the progression of injury, pro‐inflammatory marker, histological, and elasticity analyses of the buccal pouch were conducted to verify replicability and reproducibility of the injury model. The findings from this model demonstrated its ability to consistently induce injury and resolution over 28 days using an acute dose of 60 Gy. This model was developed to enhance clinical relevance when evaluating potential efficacious treatments and can now be utilized in efficacy studies to better evaluate developed therapeutics in a preclinical model that is easy to translate to clinical studies

Hippocampus Leads Ventral Striatum in Replay of Place-Reward Information

While the brain is asleep, the hippocampus plays first fiddle in the orchestra of memory; spatial information is reactivated in the hippocampus shortly in advance of emotional memory traces in the vental striatum

Principal component analysis of ensemble recordings reveals cell assemblies at high temporal resolution

Simultaneous recordings of many single neurons reveals unique insights into network processing spanning the timescale from single spikes to global oscillations. Neurons dynamically self-organize in subgroups of coactivated elements referred to as cell assemblies. Furthermore, these cell assemblies are reactivated, or replayed, preferentially during subsequent rest or sleep episodes, a proposed mechanism for memory trace consolidation. Here we employ Principal Component Analysis to isolate such patterns of neural activity. In addition, a measure is developed to quantify the similarity of instantaneous activity with a template pattern, and we derive theoretical distributions for the null hypothesis of no correlation between spike trains, allowing one to evaluate the statistical significance of instantaneous coactivations. Hence, when applied in an epoch different from the one where the patterns were identified, (e.g. subsequent sleep) this measure allows to identify times and intensities of reactivation. The distribution of this measure provides information on the dynamics of reactivation events: in sleep these occur as transients rather than as a continuous process

The spike-timing-dependent learning rule to encode spatiotemporal patterns in a network of spiking neurons

We study associative memory neural networks based on the Hodgkin-Huxley type of spiking neurons. We introduce the spike-timing-dependent learning rule, in which the time window with the negative part as well as the positive part is used to describe the biologically plausible synaptic plasticity. The learning rule is applied to encode a number of periodical spatiotemporal patterns, which are successfully reproduced in the periodical firing pattern of spiking neurons in the process of memory retrieval. The global inhibition is incorporated into the model so as to induce the gamma oscillation. The occurrence of gamma oscillation turns out to give appropriate spike timings for memory retrieval of discrete type of spatiotemporal pattern. The theoretical analysis to elucidate the stationary properties of perfect retrieval state is conducted in the limit of an infinite number of neurons and shows the good agreement with the result of numerical simulations. The result of this analysis indicates that the presence of the negative and positive parts in the form of the time window contributes to reduce the size of crosstalk term, implying that the time window with the negative and positive parts is suitable to encode a number of spatiotemporal patterns. We draw some phase diagrams, in which we find various types of phase transitions with change of the intensity of global inhibition.Comment: Accepted for publication in Physical Review

Finding the engram.

Many attempts have been made to localize the physical trace of a memory, or engram, in the brain. However, until recently, engrams have remained largely elusive. In this Review, we develop four defining criteria that enable us to critically assess the recent progress that has been made towards finding the engram. Recent \u27capture\u27 studies use novel approaches to tag populations of neurons that are active during memory encoding, thereby allowing these engram-associated neurons to be manipulated at later times. We propose that findings from these capture studies represent considerable progress in allowing us to observe, erase and express the engram

At clinically relevant concentrations the anaesthetic/amnesic thiopental but not the anticonvulsant phenobarbital interferes with hippocampal sharp wave-ripple complexes

<p>Abstract</p> <p>Background</p> <p>Many sedative agents, including anesthetics, produce explicit memory impairment by largely unknown mechanisms. Sharp-wave ripple (SPW-R) complexes are network activity thought to represent the neuronal substrate for information transfer from the hippocampal to neocortical circuits, contributing to the explicit memory consolidation. In this study we examined and compared the actions of two barbiturates with distinct amnesic actions, the general anesthetic thiopental and the anticonvulsant phenobarbital, on in vitro SPW-R activity.</p> <p>Results</p> <p>Using an in vitro model of SPW-R activity we found that thiopental (50–200 μM) significantly and concentration-dependently reduced the incidence of SPW-R events (it increased the inter-event period by 70–430 %). At the concentration of 25 μM, which clinically produces mild sedation and explicit memory impairment, thiopental significantly reduced the quantity of ripple oscillation (it reduced the number of ripples and the duration of ripple episodes by 20 ± 5%, n = 12, <it>P </it>< 0.01), and suppressed the rhythmicity of SPWs by 43 ± 15% (n = 6, <it>P </it>< 0.05). The drug disrupted the synchrony of SPWs within the CA1 region at 50 μM (by 19 ± 12%; n = 5, <it>P </it>< 0.05). Similar effects of thiopental were observed at higher concentrations. Thiopental did not affect the frequency of ripple oscillation at any of the concentrations tested (10–200 μM). Furthermore, the drug significantly prolonged single SPWs at concentrations ≥50 μM (it increased the half-width and the duration of SPWs by 35–90 %). Thiopental did not affect evoked excitatory synaptic potentials and its results on SPW-R complexes were also observed under blockade of NMDA receptors. Phenobarbital significantly accelerated SPWs at 50 and 100 μM whereas it reduced their rate at 200 and 400 μM. Furthermore, it significantly prolonged SPWs, reduced their synchrony and reduced the quantity of ripples only at the clinically very high concentration of 400 μM, reported to affect memory.</p> <p>Conclusion</p> <p>We hypothesize that thiopental, by interfering with SPW-R activity, through enhancement of the GABA_Areceptor-mediated transmission, affects memory processes which involve hippocampal circuit activation. The quantity but not the frequency of ripple oscillation was affected by the drug.</p