scholarly journals Posterior hippocampal spindle-ripples co-occur with neocortical theta-bursts and down-upstates, and phase-lock with parietal spindles during NREM sleep in humans

2019 ◽  
Author(s):  
Xi Jiang ◽  
Jorge Gonzalez-Martinez ◽  
Eric Halgren
Keyword(s):  
Hippocampal Neurons ◽  
Dorsal Hippocampus ◽  
Nrem Sleep ◽  
Alternative Mechanism ◽  
Behavioral Correlates ◽  
Specific Memory ◽  
Tightly Coupled ◽  
Conscious Recollection ◽  
Posterior Parietal ◽  
Multiple Spindle

AbstractHuman anterior and posterior hippocampus (aHC, pHC) differ in connectivity and behavioral correlates. Here we report physiological differences. During NREM sleep, the human hippocampus generates sharpwave-ripples (SWR) similar to those which in rodents mark memory replay. We show that while pHC generates SWR, it also generates about as many spindle-ripples (SSR: ripples phase-locked to local spindles). In contrast, SSR are rare in aHC. Like SWR, SSR often co-occur with neocortical theta bursts (TB), downstates (DS), spindles (SS) and upstates (US), which coordinate cortico-hippocampal interactions and facilitate consolidation in rodents. SWR co-occur with these waves in widespread cortical areas, especially fronto-central. These waves typically occur in the sequence TB-DS-SS-US, with SWR usually occurring prior to SS-US. In contrast, SSR occur ∼350 ms later, with a strong preference for co-occurrence with posterior-parietal SS. pHC-SS were strongly phase-locked with parietal-SS, and pHC-SSR were phase-coupled with pHC-SS and parietal-SS. Human SWR (and associated replay events, if any) are separated by ∼5 s on average, whereas ripples on successive SSR peaks are separated by only ∼80 ms. These distinctive physiological properties of pHC-SSR enable an alternative mechanism for hippocampal engagement with neocortex.Significance StatementRodent hippocampal neurons replay waking events during sharpwave-ripples in NREM sleep, facilitating memory transfer to a permanent cortical store. We show that human anterior hippocampus also produces sharpwave-ripples, but spindle-ripples predominate in posterior. Whereas sharpwave-ripples typically occur as cortex emerges from inactivity, spindle-ripples typically occur at peak cortical activity. Furthermore, posterior hippocampal spindle-ripples are tightly coupled to posterior parietal locations activated by conscious recollection. Finally, multiple spindle-ripples can recur within a second, whereas sharpwave-ripples are separated by about 5s. The human posterior hippocampus is considered homologous to rodent dorsal hippocampus, which is thought to be specialized for consolidation of specific memory details. We speculate that these distinct physiological characteristics of posterior hippocampal spindle-ripples may support a related function in humans.

scholarly journals Distinctive binding properties of human monoclonal LGI1 autoantibodies determine pathogenic mechanisms

Brain ◽  
2020 ◽  
Vol 143 (6) ◽  
pp. 1731-1745 ◽  
Author(s):  
Melanie Ramberger ◽  
Antonio Berretta ◽  
Jeanne M M Tan ◽  
Bo Sun ◽  
Sophia Michael ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Molecular Mechanisms ◽  
Long Term Potentiation ◽  
Serum Samples ◽  
Pathogenic Potential ◽  
Binding Characteristics ◽  
Domain Specific ◽  
Rodent Brain ◽  
Specific Memory

Abstract Autoantibodies against leucine-rich glioma inactivated 1 (LGI1) are found in patients with limbic encephalitis and focal seizures. Here, we generate patient-derived monoclonal antibodies (mAbs) against LGI1. We explore their sequences and binding characteristics, plus their pathogenic potential using transfected HEK293T cells, rodent neuronal preparations, and behavioural and electrophysiological assessments in vivo after mAb injections into the rodent hippocampus. In live cell-based assays, LGI1 epitope recognition was examined with patient sera (n = 31), CSFs (n = 11), longitudinal serum samples (n = 15), and using mAbs (n = 14) generated from peripheral B cells of two patients. All sera and 9/11 CSFs bound both the leucine-rich repeat (LRR) and the epitempin repeat (EPTP) domains of LGI1, with stable ratios of LRR:EPTP antibody levels over time. By contrast, the mAbs derived from both patients recognized either the LRR or EPTP domain. mAbs against both domain specificities showed varied binding strengths, and marked genetic heterogeneity, with high mutation frequencies. LRR-specific mAbs recognized LGI1 docked to its interaction partners, ADAM22 and ADAM23, bound to rodent brain sections, and induced internalization of the LGI1-ADAM22/23 complex in both HEK293T cells and live hippocampal neurons. By contrast, few EPTP-specific mAbs bound to rodent brain sections or ADAM22/23-docked LGI1, but all inhibited the docking of LGI1 to ADAM22/23. After intrahippocampal injection, and by contrast to the LRR-directed mAbs, the EPTP-directed mAbs showed far less avid binding to brain tissue and were consistently detected in the serum. Post-injection, both domain-specific mAbs abrogated long-term potentiation induction, and LRR-directed antibodies with higher binding strengths induced memory impairment. Taken together, two largely dichotomous populations of LGI1 mAbs with distinct domain binding characteristics exist in the affinity matured peripheral autoantigen-specific memory pools of individuals, both of which have pathogenic potential. In human autoantibody-mediated diseases, the detailed characterization of patient mAbs provides a valuable method to dissect the molecular mechanisms within polyclonal populations.

scholarly journals Bacteriorhodopsin-like channelrhodopsins: Alternative mechanism for control of cation conductance

2017 ◽  
Vol 114 (45) ◽  
pp. E9512-E9519 ◽  
Author(s):  
Oleg A. Sineshchekov ◽  
Elena G. Govorunova ◽  
Hai Li ◽  
John L. Spudich
Keyword(s):  
Proton Translocation ◽  
Laser Flash ◽  
Cation Channel ◽  
Alternative Mechanism ◽  
Cytoplasmic Channel ◽  
Cation Conductance ◽  
Proton Transfers ◽  
Channel Opening ◽  
Guillardia Theta ◽  
Tightly Coupled

The recently discovered cation-conducting channelrhodopsins in cryptophyte algae are far more homologous to haloarchaeal rhodopsins, in particular the proton pump bacteriorhodopsin (BR), than to earlier known channelrhodopsins. They uniquely retain the two carboxylate residues that define the vectorial proton path in BR in which Asp-85 and Asp-96 serve as acceptor and donor, respectively, of the photoactive site Schiff base (SB) proton. Here we analyze laser flash-induced photocurrents and photochemical conversions in Guillardia theta cation channelrhodopsin 2 (GtCCR2) and its mutants. Our results reveal a model in which the GtCCR2 retinylidene SB chromophore rapidly deprotonates to the Asp-85 homolog, as in BR. Opening of the cytoplasmic channel to cations in GtCCR2 requires the Asp-96 homolog to be unprotonated, as has been proposed for the BR cytoplasmic channel for protons. However, reprotonation of the GtCCR2 SB occurs not from the Asp-96 homolog, but by proton return from the earlier protonated acceptor, preventing vectorial proton translocation across the membrane. In GtCCR2, deprotonation of the Asp-96 homolog is required for cation channel opening and occurs >10-fold faster than reprotonation of the SB, which temporally correlates with channel closing. Hence in GtCCR2, cation channel gating is tightly coupled to intramolecular proton transfers involving the same residues that define the vectorial proton path in BR.

scholarly journals Key Role of Cytochrome C for Apoptosis Detection Using Raman Microimaging in an Animal Model of Brain Ischemia with Insulin Treatment

2019 ◽  
Vol 73 (10) ◽  
pp. 1208-1217 ◽  
Author(s):  
Vanessa Russo ◽  
Patrizio Candeloro ◽  
Natalia Malara ◽  
Gerardo Perozziello ◽  
Michelangelo Iannone ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Brain Ischemia ◽  
Hippocampal Neurons ◽  
Apoptotic Cell ◽  
Resonant Scattering ◽  
Global Ischemia ◽  
Alternative Mechanism ◽  
Mongolian Gerbils ◽  
Incident Wavelength

Brain ischemia represents a leading cause of death and disability in industrialized countries. To date, therapeutic intervention is largely unsatisfactory and novel strategies are required for getting better protection of neurons injured by cerebral blood flow restriction. Recent evidence suggests that brain insulin leads to protection of neuronal population undergoing apoptotic cell death via modulation of oxidative stress and mitochondrial cytochrome c (CytC), an effect to be better clarified. In this work, we investigate on the effect of insulin given intracerebroventricular (ICV) before inducing a transient global ischemia by bilateral occlusion of the common carotid arteries (BCCO) in Mongolian gerbils (MG). The transient (3 min) global ischemia in MG is observed to produce neurodegenerative effect mainly into CA3 hippocampal region, 72 h after cerebral blood restriction. Intracerebroventricular microinfusion of insulin significantly prevents the apoptosis of CA3 hippocampal neurons. Histological observation, after hematoxylin and eosin staining, puts in evidence the neuroprotective role of insulin, but Raman microimaging provides a clearer insight in the CytC mechanism underlying the apoptotic process. Above all, CytC has been revealed to be an outstanding, innate Raman marker for monitoring the cells status, thanks to its resonant scattering at 530 nm of incident wavelength and to its crucial role in the early stages of cells apoptosis. These data support the hypothesis of an insulin-dependent neuroprotection and antiapoptotic mechanism occurring in the brain of MG undergoing transient brain ischemia. The observed effects occurred without any peripheral change on serum glucose levels, suggesting an alternative mechanism of insulin-induced neuroprotection.

scholarly journals State-dependent pontine ensemble dynamics and interactions with cortex across sleep states

2019 ◽  
Author(s):  
Tomomi Tsunematsu ◽  
Amisha A Patel ◽  
Arno Onken ◽  
Shuzo Sakata
Keyword(s):  
Rem Sleep ◽  
Hippocampal Neurons ◽  
Specific Activity ◽  
Nrem Sleep ◽  
Dependent Manner ◽  
Sleep Regulation ◽  
Population Activity ◽  
P Waves ◽  
State Dependent ◽  
Global Coordination

AbstractThe pontine nuclei play a crucial role in sleep-wake regulation. However, pontine ensemble dynamics underlying sleep regulation remain poorly understood. By monitoring population activity in multiple pontine and adjacent brainstem areas, here we show slow, state-predictive pontine ensemble dynamics and state-dependent interactions between the pons and the cortex in mice. On a timescale of seconds to minutes, pontine populations exhibit diverse firing across vigilance states, with some of these dynamics being attributed to cell type-specific activity. Pontine population activity can predict pupil dilation and vigilance states: pontine neurons exhibit longer predictable power compared with hippocampal neurons. On a timescale of sub-seconds, pontine waves (P-waves) are observed as synchronous firing of pontine neurons primarily during rapid eye movement (REM) sleep, but also during non-REM (NREM) sleep. Crucially, P-waves functionally interact with cortical activity in a state-dependent manner: during NREM sleep, hippocampal sharp wave-ripples (SWRs) precede P-waves. On the other hand, P-waves during REM sleep are phase-locked with ongoing hippocampal theta oscillations and are followed by burst firing in a subset of hippocampal neurons. Thus, the directionality of functional interactions between the hippocampus and pons changes depending on sleep states. This state-dependent global coordination between pontine and cortical regions implicates distinct functional roles of sleep.

scholarly journals Different encoding of reward location in dorsal and ventral hippocampus

2021 ◽  
Author(s):  
Przemyslaw Jarzebowski ◽  
Y. Audrey Hay ◽  
Benjamin F. Grewe ◽  
Ole Paulsen
Keyword(s):  
Calcium Imaging ◽  
Hippocampal Neurons ◽  
Dorsal Hippocampus ◽  
Spatial Navigation ◽  
Ventral Hippocampus ◽  
Place Cells ◽  
Cognitive Map ◽  
Population Activity ◽  
Reward Seeking ◽  
Seeking Behavior

SummaryHippocampal neurons encode a cognitive map for spatial navigation1. When they fire at specific locations in the environment, they are known as place cells2. In the dorsal hippocampus place cells accumulate at current navigational goals, such as learned reward locations3–6. In the intermediate-to-ventral hippocampus (here collectively referred to as ventral hippocampus), neurons fire across larger place fields7–10 and regulate reward- seeking behavior11–16, but little is known about their involvement in reward-directed navigation. Here, we compared the encoding of learned reward locations in the dorsal and ventral hippocampus during spatial navigation. We used calcium imaging with a head- mounted microscope to track the activity of CA1 cells over multiple days during which mice learned different reward locations. In dorsal CA1 (dCA1), the overall number of active place cells increased in anticipation of reward but the recruited cells changed with the reward location. In ventral CA1 (vCA1), the activity of the same cells anticipated the reward locations. Our results support a model in which the dCA1 cognitive map incorporates a changing population of cells to encode reward proximity through increased population activity, while the vCA1 provides a reward-predictive code in the activity of a specific subpopulation of cells. Both of these location-invariant codes persisted over time, and together they provide a dual hippocampal reward-location code, assisting goal- directed navigation17, 18.

scholarly journals Increased excitability in hippocampal neurons of synaptopodin-knockout mouse

2021 ◽  
Author(s):  
Etay Aloni ◽  
Serphima Verbitzky ◽  
Lilia kushnireva ◽  
Eduard Korkotian ◽  
Menahem Segal
Keyword(s):  
Endoplasmic Reticulum ◽  
Hippocampal Neurons ◽  
Dorsal Hippocampus ◽  
Long Term Potentiation ◽  
Ca1 Neurons ◽  
Ca1 Region ◽  
Term Potentiation ◽  
Hippocampus Slice ◽  
Recorded Activity

Abstract Synaptopodin (SP) is localized within the spine apparatus, an enigmatic structure located in the neck of spines of central excitatory neurons. It serves as a link between the spine head, where the synapse is located, and the endoplasmic reticulum (ER) in the parent dendrite (Vlachos et al. 2009, Korkotian and Segal, 2011, Zhang et al. 2013). SP is also located in the axon initial segment, in association with the cisternal organelle, another structure related to endoplasmic reticulum. Extensive research using SP knockout (SPKO) mice suggests that SP has a pivotal role in structural and functional plasticity (Deller et al. 2003, Deller et al. 2007). Consequently, SPKO mice were shown to be deficient in cognitive functions, and in ability to undergo long term potentiation of reactivity to afferent stimulation (Deller et al. 2003). In contrast, neurons of SPKO mice appear to be more excitable than their wild type (wt) counterparts(Bas Orth et al, 2007). To address this discrepancy, we have now recorded activity of CA1 neurons in the mouse hippocampus slice, with both extracellular and patch recording methods. Electrophysiologically, SPKO cells in CA1 region of the dorsal hippocampus were more excitable than wt ones. In addition, exposure of mice to a complex environment caused a higher proportion of arc-expressing cells in SPKO than in wt mice hippocampus. These experiments indicate that higher excitability and higher expression of arc staining may reflect SP deficiency in the hippocampus of adult SPKO mice.

scholarly journals Glutamatergic drive along the septo-temporal axis of hippocampus boosts prelimbic oscillations in the neonatal mouse

2017 ◽  
Author(s):  
Joachim Ahlbeck ◽  
Lingzhen Song ◽  
Mattia Chini ◽  
Antonio Candela ◽  
Sebastian H. Bitzenhofer ◽  
...  
Keyword(s):  
Long Range ◽  
Hippocampal Neurons ◽  
High Efficiency ◽  
Dorsal Hippocampus ◽  
Phase Locking ◽  
Ventral Hippocampus ◽  
Neuronal Firing ◽  
Projection Neurons ◽  
List Type ◽  
Axonal Projections

SUMMARYThe long-range coupling within prefrontal-hippocampal networks that account for cognitive performance emerges early in life. The discontinuous hippocampal theta bursts have been proposed to drive the generation of neonatal prefrontal oscillations, yet the cellular substrate of these early interactions is still unresolved. Here, we selectively target optogenetic manipulation of glutamatergic projection neurons in the CA1 area of either dorsal or intermediate/ventral hippocampus at neonatal age to elucidate their contribution to the emergence of prefrontal oscillatory entrainment. We show that despite stronger theta and ripples power in dorsal hippocampus, the prefrontal cortex is mainly coupled with intermediate/ventral hippocampus by phase-locking of neuronal firing via dense direct axonal projections. Theta band-confined activation by light of pyramidal neurons in intermediate/ventral but not dorsal CA1 that were transfected by in utero electroporation with high-efficiency channelrhodopsin boosts prefrontal oscillations. Our data causally elucidates the cellular origin of the long-range coupling in the developing brain.HighlightsNeonatal theta bursts, sharp waves and ripples vary along septo-temporal axisHippocampal activity times prefrontal oscillations via direct axonal projectionsSelective hippocampal targeting along septo-temporal axis causes precise firingLight stimulation of hippocampal neurons at 8 Hz boosts prefrontal oscillations

scholarly journals GABAA and NMDA receptor density alterations and their behavioral correlates in the gestational methylazoxymethanol acetate model for schizophrenia

2021 ◽  
Author(s):  
Amanda Kiemes ◽  
Felipe V. Gomes ◽  
Diana Cash ◽  
Daniela L. Uliana ◽  
Camilla Simmons ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Dorsal Hippocampus ◽  
Ventral Hippocampus ◽  
Gabaergic Interneuron ◽  
Receptor Density ◽  
Behavioral Correlates ◽  
Pharmacological Agents ◽  
Methylazoxymethanol Acetate ◽  
Therapeutic Mechanism

AbstractHippocampal hyperactivity driven by GABAergic interneuron deficits and NMDA receptor hypofunction is associated with the hyperdopaminergic state often observed in schizophrenia. Furthermore, previous research in the methylazoxymethanol acetate (MAM) rat model has demonstrated that repeated peripubertal diazepam administration can prevent the emergence of adult hippocampal hyperactivity, dopamine-system hyperactivity, and associated psychosis-relevant behaviors. Here, we sought to characterize hippocampal GABAA and NMDA receptors in MAM-treated rats and to elucidate the receptor mechanisms underlying the promising effects of peripubertal diazepam exposure. Quantitative receptor autoradiography was used to measure receptor density in the dorsal hippocampus CA1, ventral hippocampus CA1, and ventral subiculum. Specifically, [3H]-Ro15-4513 was used to quantify the density of α5GABAA receptors (α5GABAAR), [3H]-flumazenil to quantify α1-3;5GABAAR, and [3H]-MK801 to quantify NMDA receptors. MAM rats exhibited anxiety and schizophrenia-relevant behaviors as measured by elevated plus maze and amphetamine-induced hyperlocomotion (AIH), although diazepam only partially rescued these behaviors. α5GABAAR density was reduced in MAM-treated rats in all hippocampal sub-regions, and negatively correlated with AIH. Ventral hippocampus CA1 α5GABAAR density was positively correlated with anxiety-like behavior. Dorsal hippocampus CA1 NMDA receptor density was increased in MAM-treated rats, and positively correlated with AIH. [3H]-flumazenil revealed no significant effects. Finally, we found no significant effect of diazepam treatment on receptor densities, potentially related to the only partial rescue of schizophrenia-relevant phenotypes. Overall, our findings provide first evidence of α5GABAAR and NMDA receptor abnormalities in the MAM model, suggesting that more selective pharmacological agents may become a novel therapeutic mechanism in schizophrenia.

scholarly journals The spatial distribution of attention predicts familiarity strength during encoding and retrieval

2019 ◽  
Author(s):  
Michelle Marie Ramey ◽  
John M. Henderson ◽  
Andrew P. Yonelinas
Keyword(s):  
Spatial Distribution ◽  
Eye Movements ◽  
Eye Movement ◽  
Attentional Processes ◽  
Memory Processing ◽  
Memory Processes ◽  
Specific Memory ◽  
Conscious Recollection ◽  
Past Experiences ◽  
Encoding And Retrieval

The memories we form are determined by what we attend to, and conversely, what we attend to is influenced by our memory for past experiences. Although we know that shifts of attention via eye movements are related to memory during encoding and retrieval, the role of specific memory processes in this relationship is unclear. There is evidence that attention may be especially important for some forms of memory (i.e., conscious recollection), and less so for others (i.e., familiarity-based recognition and unconscious influences of memory), but results are conflicting with respect to both the memory processes and eye movement patterns involved. To address this, we used a confidence-based method of isolating eye movement indices of spatial attention that are related to different memory processes (i.e., recollection, familiarity strength, and unconscious memory) during encoding and retrieval of real-world scenes. We also developed a new method of measuring the dispersion of eye movements, which proved to be more sensitive to memory processing than previously used measures. Specifically, in two studies, we found that familiarity strength—that is, changes in subjective reports of memory confidence—increased with i) more dispersed patterns of viewing during encoding, ii) less dispersed viewing during retrieval, and iii) greater overlap in regions viewed between encoding and retrieval (i.e., resampling). Recollection was also related to these eye movements in a similar manner, though the associations with recollection were less consistent across experiments. Furthermore, we found no evidence for effects related to unconscious influences of memory. These findings indicate that attentional processes during viewing may not preferentially relate to recollection, and that the spatial distribution of eye movements is directly related to familiarity-based memory during encoding and retrieval.

scholarly journals Neurosharing: large-scale data sets (spike, LFP) recorded from the hippocampal-entorhinal system in behaving rats

F1000Research ◽  
2014 ◽  
Vol 3 ◽  
pp. 98 ◽  
Author(s):  
Kenji Mizuseki ◽  
Kamran Diba ◽  
Eva Pastalkova ◽  
Jeff Teeters ◽  
Anton Sirota ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Large Scale ◽  
Dorsal Hippocampus ◽  
Field Potential ◽  
Data Sets ◽  
Data Set ◽  
Large Scale Data ◽  
Silicon Based ◽  
Spike Waveforms ◽  
Wave Shapes

Using silicon-based recording electrodes, we recorded neuronal activity of the dorsal hippocampus and dorsomedial entorhinal cortex from behaving rats. The entorhinal neurons were classified as principal neurons and interneurons based on monosynaptic interactions and wave-shapes. The hippocampal neurons were classified as principal neurons and interneurons based on monosynaptic interactions, wave-shapes and burstiness. The data set contains recordings from 7,736 neurons (6,100 classified as principal neurons, 1,132 as interneurons, and 504 cells that did not clearly fit into either category) obtained during 442 recording sessions from 11 rats (a total of 204.5 hours) while they were engaged in one of eight different behaviours/tasks. Both original and processed data (time stamp of spikes, spike waveforms, result of spike sorting and local field potential) are included, along with metadata of behavioural markers. Community-driven data sharing may offer cross-validation of findings, refinement of interpretations and facilitate discoveries.

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