Synchronicity of excitatory inputs drives hippocampal networks to distinct oscillatory patterns

Geschwill, Pascal; Kaiser, Martin E.; Grube, Paul; Lehmann, Nadja; Thome, Christian; Draguhn, Andreas; Hollnagel, Jan‐Oliver; Both, Martin

doi:10.1002/hipo.23214

Cited by 6 publications

(4 citation statements)

References 57 publications

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“…Like the proposed ripple generation mechanism for random networks, sequence generation and the thereby evoked oscillations are based on the prominent excitatory-inhibitory and inhibitory-excitatory connectivity in the hippocampal region CA1. The basic idea is as follows: CA3 excites an initial, zeroth group of CA1 E cells to spike within a short time interval [ 111 ]. This group excites all CA1 I cells involved in the dynamical pattern, except for the first group of I cells.…”

Section: Resultsmentioning

confidence: 99%

High-frequency oscillations and sequence generation in two-population models of hippocampal region CA1

Braun

Memmesheimer

2022

PLoS Comput Biol

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Hippocampal sharp wave/ripple oscillations are a prominent pattern of collective activity, which consists of a strong overall increase of activity with superimposed (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. We start by investigating its ability to generate ripple oscillations using extensive simulations. Using biologically plausible parameters, we find that short pulses of external excitation triggering excitatory cell spiking are required for sharp/wave ripple generation with oscillation patterns similar to in vivo observations. Our model has plausible values for single neuron, synapse and connectivity parameters, random connectivity and no strong feedforward drive to the inhibitory population. 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 denotes phases of silence in specific basket cell groups, which induce 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.

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Section: Resultsmentioning

confidence: 99%

High-frequency oscillations and sequence generation in two-population models of hippocampal region CA1

Braun

Memmesheimer

2022

PLoS Comput Biol

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“…Input from the CA3 region is also an important modulator of SWR activity and gamma activity. In vitro studies have observed that SWRs and gamma oscillations can be directly modulated by modulating the activity of excitatory pyramidal neurons of the CA3 layer ( Geschwill et al, 2020 ). In addition, the medial entorhinal cortex (mEnt) is the major input of somatosensory information to the hippocampus ( Axmacher et al, 2008 , Igarashi et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Alterations in theta-gamma coupling and sharp wave-ripple, signs of prodromal hippocampal network impairment in the TgF344-AD rat model

Berg

Toen

Verhoye

et al. 2023

Front. Aging Neurosci.

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Alzheimer’s disease (AD) is a severe neurodegenerative disorder caused by the accumulation of toxic proteins, amyloid-beta (Aβ) and tau, which eventually leads to dementia. Disease-modifying therapies are still lacking, due to incomplete insights into the neuropathological mechanisms of AD. Synaptic dysfunction is known to occur before cognitive symptoms become apparent and recent studies have demonstrated that imbalanced synaptic signaling drives the progression of AD, suggesting that early synaptic dysfunction could be an interesting therapeutic target. Synaptic dysfunction results in altered oscillatory activity, which can be detected with electroencephalography and electrophysiological recordings. However, the majority of these studies have been performed at advanced stages of AD, when extensive damage and cognitive symptoms are already present. The current study aimed to investigate if the hippocampal oscillatory activity is altered at pre-plaque stages of AD. The rats received stereotactic surgery to implant a laminar electrode in the CA1 layer of the right hippocampus. Electrophysiological recordings during two consecutive days in an open field were performed in 4–5-month-old TgF344-AD rats when increased concentrations of soluble Aβ species were observed in the brain, in the absence of Aβ-plaques. We observed a decreased power of high theta oscillations in TgF344-AD rats compared to wild-type littermates. Sharp wave-ripple (SWR) analysis revealed an increased SWR power and a decreased duration of SWR during quiet wake in TgF344-AD rats. The alterations in properties of SWR and the increased power of fast oscillations are suggestive of neuronal hyperexcitability, as has been demonstrated to occur during presymptomatic stages of AD. In addition, decreased strength of theta-gamma coupling, an important neuronal correlate of memory encoding, was observed in the TgF344-AD rats. Theta-gamma phase amplitude coupling has been associated with memory encoding and the execution of cognitive functions. Studies have demonstrated that mild cognitive impairment patients display decreased coupling strength, similar to what is described here. The current study demonstrates altered hippocampal network activity occurring at pre-plaque stages of AD and provides insights into prodromal network dysfunction in AD. The alterations observed could aid in the detection of AD during presymptomatic stages.

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“…Previous work has revealed that propagating SPW-R involves strong synaptic excitation of CA1 pyramidal cells followed by pronounced, rhythmic perisomatic inhibition at ripple frequency (Ellender et al, 2010 ; Maier et al, 2011 ; Gan et al, 2017 ; Geschwill et al, 2020 ). We, therefore, analyzed the contribution of inhibitory and excitatory synaptic input during SPW-R in animals from enriched environments compared to motor controls.…”

Section: Resultsmentioning

confidence: 99%

Enriched Environment Modulates Sharp Wave-Ripple (SPW-R) Activity in Hippocampal Slices

Landeck

Kaiser

Hefter

et al. 2021

Front. Neural Circuits

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Behavioral flexibility depends on neuronal plasticity which forms and adapts the central nervous system in an experience-dependent manner. Thus, plasticity depends on interactions between the organism and its environment. A key experimental paradigm for studying this concept is the exposure of rodents to an enriched environment (EE), followed by studying differences to control animals kept under standard conditions (SC). While multiple changes induced by EE have been found at the cellular-molecular and cognitive-behavioral levels, little is known about EE-dependent alterations at the intermediate level of network activity. We, therefore, studied spontaneous network activity in hippocampal slices from mice which had previously experienced EE for 10–15 days. Compared to control animals from standard conditions (SC) and mice with enhanced motor activity (MC) we found several differences in sharp wave-ripple complexes (SPW-R), a memory-related activity pattern. Sharp wave amplitude, unit firing during sharp waves, and the number of superimposed ripple cycles were increased in tissue from the EE group. On the other hand, spiking precision with respect to the ripple oscillations was reduced. Recordings from single pyramidal cells revealed a reduction in synaptic inhibition during SPW-R together with a reduced inhibition-excitation ratio. The number of inhibitory neurons, including parvalbumin-positive interneurons, was unchanged. Altered activation or efficacy of synaptic inhibition may thus underlie changes in memory-related network activity patterns which, in turn, may be important for the cognitive-behavioral effects of EE exposure.

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Synchronicity of excitatory inputs drives hippocampal networks to distinct oscillatory patterns

Cited by 6 publications

References 57 publications

High-frequency oscillations and sequence generation in two-population models of hippocampal region CA1

High-frequency oscillations and sequence generation in two-population models of hippocampal region CA1

Alterations in theta-gamma coupling and sharp wave-ripple, signs of prodromal hippocampal network impairment in the TgF344-AD rat model

Enriched Environment Modulates Sharp Wave-Ripple (SPW-R) Activity in Hippocampal Slices

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