scholarly journals CA2 inhibition reduces the precision of hippocampal assembly reactivation

2020 ◽  
Author(s):  
Hongshen He ◽  
Roman Boehringer ◽  
Arthur J.Y. Huang ◽  
Eric T.N. Overton ◽  
Denis Polygalov ◽  
...  
Keyword(s):  
Pyramidal Cell ◽  
Crucial Role ◽  
Pyramidal Cells ◽  
Population Activity ◽  
Ca1 Neurons ◽  
Neuronal Ensembles ◽  
Sharp Wave

AbstractThe structured reactivation of hippocampal neuronal ensembles during fast synchronous oscillatory events termed sharp-wave ripples (SWRs) has been suggested to play a crucial role in the storage and use of memory. Activity in both the CA2 and CA3 subregions can proceed this population activity in CA1 and chronic inhibition of either region alters SWR oscillations. However, the precise contribution of CA2 to the oscillation, as well as to the reactivation of CA1 neurons within it, remains unclear. Here we employ chemogenetics to transiently silence CA2 pyramidal cells in mice and observe that while SWRs still occur, the reactivation of CA1 pyramidal cell ensembles within the events lose both temporal and informational precision. These observations suggest that CA2 activity contributes to the fidelity of experience-dependent hippocampal replay.

scholarly journals Mild metabolic stress is sufficient to disturb the formation of pyramidal cell ensembles during gamma oscillations

2019 ◽  
Vol 40 (12) ◽  
pp. 2401-2415 ◽  
Author(s):  
Shehabeldin Elzoheiry ◽  
Andrea Lewen ◽  
Justus Schneider ◽  
Martin Both ◽  
Dimitri Hefter ◽  
...  
Keyword(s):  
Pyramidal Cell ◽  
Metabolic Stress ◽  
Pyramidal Cells ◽  
Gamma Oscillations ◽  
System Level ◽  
Attention And Memory ◽  
Neuronal Ensembles ◽  
Brain Functions ◽  
Fast Spiking ◽  
Underlying Mechanisms

Disturbances of cognitive functions occur rapidly during acute metabolic stress. However, the underlying mechanisms are not fully understood. Cortical gamma oscillations (30–100 Hz) emerging from precise synaptic transmission between excitatory principal neurons and inhibitory interneurons, such as fast-spiking GABAergic basket cells, are associated with higher brain functions, like sensory perception, selective attention and memory formation. We investigated the alterations of cholinergic gamma oscillations at the level of neuronal ensembles in the CA3 region of rat hippocampal slice cultures. We combined electrophysiology, calcium imaging (CamKII.GCaMP6f) and mild metabolic stress that was induced by rotenone, a lipophilic and highly selective inhibitor of complex I in the respiratory chain of mitochondria. The detected pyramidal cell ensembles showing repetitive patterns of activity were highly sensitive to mild metabolic stress. Whereas such synchronised multicellular activity diminished, the overall activity of individual pyramidal cells was unaffected. Additionally, mild metabolic stress had no effect on the rate of action potential generation in fast-spiking neural units. However, the partial disinhibition of slow-spiking neural units suggests that disturbances of ensemble formation likely result from alterations in synaptic inhibition. Our study bridges disturbances on the (multi-)cellular and network level to putative cognitive impairment on the system level.

scholarly journals High-frequency oscillations and replay in a two-population model of hippocampal region CA1

2021 ◽  
Author(s):  
Wilhelm Braun ◽  
Raoul-Martin Memmesheimer
Keyword(s):  
Pyramidal Cell ◽  
High Frequency ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Basket Cell ◽  
Hippocampal Region ◽  
Short Pulses ◽  
Sharp Wave ◽  
High Frequency Oscillations

Hippocampal sharp wave/ripple oscillations are a prominent pattern of collective activity, which consists of a strong overall increase of activity with onmodulated (140 − 200 Hz) ripple oscillations. Despite its prominence and its experimentally demonstrated importance for memory consolidation, the mechanisms underlying its generation are to date not understood. Several models assume that recurrent networks of inhibitory cells alone can explain the generation and main characteristics of the ripple oscillations. Recent experiments, however, indicate that in addition to inhibitory basket cells, the pattern requires in vivo the activity of the local population of excitatory pyramidal cells. Here we study a model for networks in the hippocampal region CA1 incorporating such a local excitatory population of pyramidal neurons and investigate its ability to generate ripple oscillations using extensive simulations. We find that with biologically plausible values for single neuron, synapse and connectivity parameters, random connectivity and absent strong feedforward drive to the inhibitory population, oscillation patterns similar to in vivo sharp wave/ripples can only be generated if excitatory cell spiking is triggered by short pulses of external excitation. Specifically, whereas temporally broad excitation can lead to high-frequency oscillations in the ripple range, sparse pyramidal cell activity is only obtained with pulse-like external CA3 excitation. Further simulations indicate that such short pulses could originate from dendritic spikes in the apical or basal dendrites of CA1 pyramidal cells, which are triggered by coincident spike arrivals from hippocampal region CA3. Finally we show that replay of sequences by pyramidal neurons and ripple oscillations can arise intrinsically in CA1 due to structured connectivity that gives rise to alternating excitatory pulse and inhibitory gap coding; the latter implies phases of silence in specific basket cell groups and selective disinhibition of groups of pyramidal neurons. This general mechanism for sequence generation leads to sparse pyramidal cell and dense basket cell spiking, does not rely on synfire chain-like feedforward excitation and may be relevant for other brain regions as well.

scholarly journals A new reduced-morphology model for CA1 pyramidal cells and its validation and comparison with other models using HippoUnit

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Matus Tomko ◽  
Lubica Benuskova ◽  
Peter Jedlicka
Keyword(s):  
Pyramidal Cell ◽  
Pyramidal Neurons ◽  
Standardized Test ◽  
Dendritic Tree ◽  
Pyramidal Cells ◽  
Computational Time ◽  
Ca1 Neurons ◽  
Ca1 Pyramidal Cells ◽  
Morphology Model ◽  
Complex Models

AbstractModeling long-term neuronal dynamics may require running long-lasting simulations. Such simulations are computationally expensive, and therefore it is advantageous to use simplified models that sufficiently reproduce the real neuronal properties. Reducing the complexity of the neuronal dendritic tree is one option. Therefore, we have developed a new reduced-morphology model of the rat CA1 pyramidal cell which retains major dendritic branch classes. To validate our model with experimental data, we used HippoUnit, a recently established standardized test suite for CA1 pyramidal cell models. The HippoUnit allowed us to systematically evaluate the somatic and dendritic properties of the model and compare them to models publicly available in the ModelDB database. Our model reproduced (1) somatic spiking properties, (2) somatic depolarization block, (3) EPSP attenuation, (4) action potential backpropagation, and (5) synaptic integration at oblique dendrites of CA1 neurons. The overall performance of the model in these tests achieved higher biological accuracy compared to other tested models. We conclude that, due to its realistic biophysics and low morphological complexity, our model captures key physiological features of CA1 pyramidal neurons and shortens computational time, respectively. Thus, the validated reduced-morphology model can be used for computationally demanding simulations as a substitute for more complex models.

Level of Arousal During the Small Irregular Activity State in the Rat Hippocampal EEG

2004 ◽  
Vol 91 (6) ◽  
pp. 2649-2657 ◽  
Author(s):  
Beata Jarosiewicz ◽  
William E. Skaggs
Keyword(s):  
Slow Wave Sleep ◽  
Power Spectra ◽  
Pyramidal Cells ◽  
Auditory Stimuli ◽  
Sleep State ◽  
Population Activity ◽  
Ca1 Pyramidal Cells ◽  
Emg Amplitude ◽  
Current Location ◽  
Activity State

The sleeping rat cycles between two well-characterized hippocampal physiological states, large irregular activity (LIA) during slow-wave sleep (SWS) and theta activity during rapid-eye-movement sleep (REM). A third, less well-characterized electroencephalographic (EEG) state, termed “small irregular activity” (SIA), has been reported to occur when an animal is startled out of sleep without moving and during active waking when it abruptly freezes. We recently found that the hippocampal population activity of a spontaneous sleep state whose EEG resembles SIA reflects the rat's current location in space, suggesting that it is also a state of heightened arousal. To test whether this spontaneous SIA state corresponds to the SIA state reported in the literature and to compare the level of arousal during SIA to the other well-characterized physiological states, we recorded unit activity from ensembles of hippocampal CA1 pyramidal cells, EEG from the hippocampus and the neocortex, and electromyography (EMG) from the dorsal neck musculature in rats presented with auditory stimuli while foraging for randomly scattered food pellets and while sleeping. Auditory stimuli presented during sleep reliably induced SIA episodes very similar to spontaneous SIA in hippocampal and neocortical EEG amplitudes and power spectra, EMG amplitude, and CA1 population activity. Both spontaneous and elicited SIA exhibited neocortical desynchronization, and both had EMG amplitude comparable to that of waking LIA. We conclude based on this and other evidence that spontaneous SIA and elicited SIA correspond to a single state and that the level of arousal in SIA is higher than in the well-characterized sleep states but lower than the active theta state.

Single-unit analysis of different hippocampal cell types during classical conditioning of rabbit nictitating membrane response

1983 ◽  
Vol 50 (5) ◽  
pp. 1197-1219 ◽  
Author(s):  
T. W. Berger ◽  
P. C. Rinaldi ◽  
D. J. Weisz ◽  
R. F. Thompson
Keyword(s):  
Classical Conditioning ◽  
Pyramidal Cell ◽  
Action Potentials ◽  
Pyramidal Cells ◽  
Cell Types ◽  
Firing Frequency ◽  
Spontaneous Firing ◽  
Nictitating Membrane ◽  
Nictitating Membrane Response ◽  
Firing Characteristics

Extracellular single-unit recordings from neurons in the CA1 and CA3 regions of the dorsal hippocampus were monitored during classical conditioning of the rabbit nictitating membrane response. Neurons were classified as different cell types using response to fornix stimulation (i.e., antidromic or orthodromic activation) and spontaneous firing characteristics as criteria. Results showed that hippocampal pyramidal neurons exhibit learning-related neural plasticity that develops gradually over the course of classical conditioning. The learning-dependent pyramidal cell response is characterized by an increase in frequency of firing within conditioning trials and a within-trial pattern of discharge that correlates strongly with amplitude-time course of the behavioral response. In contrast, pyramidal cell activity recorded from control animals given unpaired presentations of the conditioned and unconditioned stimulus (CS and UCS) does not show enhanced discharge rates with repeated stimulation. Previous studies of hippocampal cellular electrophysiology have described what has been termed a theta-cell (19-21, 45), the activity of which correlates with slow-wave theta rhythm generated in the hippocampus. Neurons classified as theta-cells in the present study exhibit responses during conditioning that are distinctly different than pyramidal cells. theta-Cells respond during paired conditioning trials with a rhythmic bursting; the between-burst interval occurs at or near 8 Hz. In addition, two different types of theta-cells were distinguishable. One type of theta-cell increases firing frequency above pretrial levels while displaying the theta bursting pattern. The other type decreases firing frequency below pretrial rates while showing a theta-locked discharge. In addition to pyramidal and theta-neurons, several other cell types recorded in or near the pyramidal cell layer could be distinguished. One cell type was distinctive in that it could be activated with a short, invariant latency following fornix stimulation, but spontaneous action potentials of such neurons could not be collided with fornix shock-induced action potentials. These neurons exhibit a different profile of spontaneous firing characteristics than those of antidromically identified pyramidal cells. Nevertheless, neurons in this noncollidable category display the same learning-dependent response as pyramidal cells. It is suggested that the noncollidable neurons represent a subpopulation of pyramidal cells that do not project an axon via the fornix but project, instead, to other limbic cortical regions.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals A computational study of suppression of sharp wave ripple complexes by controlling calcium and gap junctions in pyramidal cells

Bioengineered ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 2603-2615
Author(s):  
Muhammad Mushtaq ◽  
Rizwan ul Haq ◽  
Waqas Anwar ◽  
Lisa Marshall ◽  
Maxim Bazhenov ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Computational Study ◽  
Pyramidal Cells ◽  
Sharp Wave

Major Role For Tonic GABAA Conductances in Anesthetic Suppression of Intrinsic Neuronal Excitability

2004 ◽  
Vol 92 (3) ◽  
pp. 1658-1667 ◽  
Author(s):  
Mark C. Bieda ◽  
M. Bruce MacIver
Keyword(s):  
Synaptic Transmission ◽  
Neuronal Excitability ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Intrinsic Excitability ◽  
High Potassium ◽  
Ca1 Neurons ◽  
Adult Rat ◽  
Adult Rat Brain ◽  
Sites Of Action

Anesthetics appear to produce neurodepression by altering synaptic transmission and/or intrinsic neuronal excitability. Propofol, a widely used anesthetic, has proposed effects on many targets, ranging from sodium channels to GABAA inhibition. We examined effects of propofol on the intrinsic excitability of hippocampal CA1 neurons (primarily interneurons) recorded from adult rat brain slices. Propofol strongly depressed action potential production induced by DC injection, synaptic stimulation, or high-potassium solutions. Propofol-induced depression of intrinsic excitability was completely reversed by bicuculline and picrotoxin but was strychnine-insensitive, implicating GABAA but not glycine receptors. Propofol strongly enhanced inhibitory postsynaptic currents (IPSCs) and induced a tonic GABAA-mediated current. We pharmacologically differentiated tonic and phasic (synaptic) GABAA-mediated inhibition using the GABAA receptor antagonist SR95531 (gabazine). Gabazine (20 μM) completely blocked both evoked and spontaneous IPSCs but failed to block the propofol-induced depression of intrinsic excitability, implicating tonic, but not phasic, GABAA inhibition. Glutamatergic synaptic responses were not altered by propofol (≤30 μM). Similar results were found in both interneurons and pyramidal cells and with the chemically unrelated anesthetic thiopental. These results suggest that suppression of CA1 neuron intrinsic excitability, by these anesthetics, is largely due to activation of tonic GABAA conductances; although other sites of action may play important roles in affecting synaptic transmission, which also can produce strong neurodepression. We propose that for some anesthetics, suppression of intrinsic excitability, mediated by tonic GABAA conductances, operates in conjunction with effects on synaptic transmission, mediated by other mechanisms, to depress hippocampal function during anesthesia.

scholarly journals Separable actions of acetylcholine and noradrenaline on neuronal ensemble formation in hippocampal CA3 circuits

2021 ◽  
Vol 17 (10) ◽  
pp. e1009435
Author(s):  
Luke Y. Prince ◽  
Travis Bacon ◽  
Rachel Humphries ◽  
Krasimira Tsaneva-Atanasova ◽  
Claudia Clopath ◽  
...  
Keyword(s):  
Granule Cells ◽  
Mossy Fiber ◽  
Pyramidal Cells ◽  
Recurrent Network ◽  
Memory Storage ◽  
Neuronal Ensembles ◽  
Hippocampal Ca3 ◽  
Ca3 Pyramidal Cells ◽  
Episodic Memories ◽  
Mossy Fiber Pathway

In the hippocampus, episodic memories are thought to be encoded by the formation of ensembles of synaptically coupled CA3 pyramidal cells driven by sparse but powerful mossy fiber inputs from dentate gyrus granule cells. The neuromodulators acetylcholine and noradrenaline are separately proposed as saliency signals that dictate memory encoding but it is not known if they represent distinct signals with separate mechanisms. Here, we show experimentally that acetylcholine, and to a lesser extent noradrenaline, suppress feed-forward inhibition and enhance Excitatory–Inhibitory ratio in the mossy fiber pathway but CA3 recurrent network properties are only altered by acetylcholine. We explore the implications of these findings on CA3 ensemble formation using a hierarchy of models. In reconstructions of CA3 pyramidal cells, mossy fiber pathway disinhibition facilitates postsynaptic dendritic depolarization known to be required for synaptic plasticity at CA3-CA3 recurrent synapses. We further show in a spiking neural network model of CA3 how acetylcholine-specific network alterations can drive rapid overlapping ensemble formation. Thus, through these distinct sets of mechanisms, acetylcholine and noradrenaline facilitate the formation of neuronal ensembles in CA3 that encode salient episodic memories in the hippocampus but acetylcholine selectively enhances the density of memory storage.

Nonlinear Frequency-Dependent Synchronization in the Developing Hippocampus

1999 ◽  
Vol 82 (1) ◽  
pp. 202-208 ◽  
Author(s):  
Liset Menendez de la Prida ◽  
Juan V. Sanchez-Andres
Keyword(s):  
Ampa Receptors ◽  
Action Potentials ◽  
Mossy Fibers ◽  
Pyramidal Cells ◽  
Time Interval ◽  
Nonlinear Frequency ◽  
Population Activity ◽  
Frequency Threshold ◽  
Hippocampal Networks ◽  
Full Synchronization

Synchronous population activity is present both in normal and pathological conditions such as epilepsy. In the immature hippocampus, synchronous bursting is an electrophysiological conspicuous event. These bursts, known as giant depolarizing potentials (GDPs), are generated by the synchronized activation of interneurons and pyramidal cells via GABAA, N-methyl-d-aspartate, and AMPA receptors. Nevertheless the mechanism leading to this synchronization is still controversial. We have investigated the conditions under which synchronization arises in developing hippocampal networks. By means of simultaneous intracellular recordings, we show that GDPs result from local cooperation of active cells within an integration period prior to their onset. During this time interval, an increase in the number of excitatory postsynaptic potentials (EPSPs) takes place building up full synchronization between cells. These EPSPs are correlated with individual action potentials simultaneously occurring in neighboring cells. We have used EPSP frequency as an indicator of the neuronal activity underlying GDP generation. By comparing EPSP frequency with the occurrence of synchronized GDPs between CA3 and the fascia dentata (FD), we found that GDPs are fired in an all-or-none manner, which is characterized by a specific threshold of EPSP frequency from which synchronous GDPs emerge. In FD, the EPSP frequency-threshold for GDP onset is 17 Hz. GDPs are triggered similarly in CA3 by appropriate periodic stimulation of mossy fibers. The frequency threshold for CA3 GDP onset is 12 Hz. These findings clarify the local mechanism of synchronization underlying bursting in the developing hippocampus, indicating that GDPs are fired when background levels of EPSPs or action potentials have built up full synchronization by firing at specific frequencies (>12 Hz). Our results also demonstrate that spontaneous EPSPs and action potentials are important for the initiation of synchronous bursts in the developing hippocampus.

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