A model of cholinergic suppression of hippocampal ripples through disruption of balanced excitation/inhibition

Melonakos, Eric D.; White, John A.; Fernandez, Fernando R.

doi:10.1002/hipo.23051

Cited by 8 publications

(13 citation statements)

References 71 publications

(133 reference statements)

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“…The designed models are therefore of the pyramidal interneuron ripple class. Related are previous interneuron network ripple models [ 21 , 26 , 28 ], other pyramidal interneuron network HFO models [ 21 , 34 , 38 ] and pyramidal neuron network ripple models [ 41 , 42 ]. Compared to pure interneuron network ripple models, the inclusion of pyramidal cells and the condition of their sparse firing renders the generation of high frequency oscillations in interneuron network ripple models as well as in pyramidal interneuron network ripple models challenging.…”

Section: Discussionmentioning

confidence: 99%

“…If the interneuron network alone can already oscillate due to its recurrent inhibition, adding an excitatory population yields, for weak synchrony, a compromise between the oscillations that emerge due to the two mechanisms [ 23 , 34 ] or, for strong synchrony, competition between them [ 33 , 37 ]. Networks of the former, weakly synchronized type have been suggested as model for ripple oscillations [ 34 , 38 ]. Adding the excitatory population usually decreases the oscillation frequency of the network, but can also increase it [ 23 , 34 ].…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

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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“…Optogenetic activation of MS cholinergic neurons during SWS suppresses hippocampal ripple oscillations (Vandecasteele et al, 2014). Computational studies suggest an unbalanced excitation/ inhibition behind such a suppression effect (Melonakos et al, 2019). But the neural mechanism underlying such a phenomenon is still elusive.…”

Section: Introductionmentioning

confidence: 99%

The Firing of Theta State-Related Septal Cholinergic Neurons Disrupt Hippocampal Ripple Oscillations via Muscarinic Receptors

Zhang

Wang

et al. 2020

J. Neurosci.

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The septo-hippocampal cholinergic system is critical for hippocampal learning and memory. However, a quantitative description of the in vivo firing patterns and physiological function of medial septal (MS) cholinergic neurons is still missing. In this study, we combined optogenetics with multichannel in vivo recording and recorded MS cholinergic neuron firings in freely behaving male mice for 5.5-72 h. We found that their firing activities were highly correlated with hippocampal theta states. MS cholinergic neurons were highly active during theta-dominant epochs, such as active exploration and rapid eye movement sleep, but almost silent during nontheta epochs, such as slow-wave sleep (SWS). Interestingly, optogenetic activation of these MS cholinergic neurons during SWS suppressed CA1 ripple oscillations. This suppression could be rescued by muscarinic M 2 or M 4 receptor antagonists. These results suggest the following important physiological function of MS cholinergic neurons: maintaining high hippocampal acetylcholine level by persistent firing during theta epochs, consequently suppressing ripples and allowing theta oscillations to dominate.

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“…On the other hand, we find that simply increasing the level of external excitation to increase the oscillation frequency usually results in too much E cell spiking, which renders the models unsuitable to describe ripple oscillations. Previous two-population models for HFOs have assumed connection probabilities [27,29,37,117] and/or spiking dynamics [25,29,37,117] that do not fit the situation in CA1 [1,20,57]. Characteristic for the spiking activity during CA1 SPW/Rs is that they are a mixture of two often considered oscillation types: strongly synchronized [36] and weakly synchronized oscillations [25,27,37].…”

Section: Discussionmentioning

confidence: 99%

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

Braun

Memmesheimer

2021

Preprint

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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 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.

show abstract

A model of cholinergic suppression of hippocampal ripples through disruption of balanced excitation/inhibition

Cited by 8 publications

References 71 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

The Firing of Theta State-Related Septal Cholinergic Neurons Disrupt Hippocampal Ripple Oscillations via Muscarinic Receptors

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

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