The effects of cholinergic neuromodulation on neuronal phase-response curves of modeled cortical neurons

Stiefel, Klaus M.; Gutkin, Boris; Sejnowski, Terrence J.

doi:10.1007/s10827-008-0111-9

Cited by 91 publications

(154 citation statements)

References 35 publications

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“…For example, the same group found experimentally that pyramidal neurons acted as integrators in vitro, but when in vivo activity was mimicked they changed into a resonator . Neuromodulators such as acetylcholine and dopamine are known to modulate adaptation and theoretical and experimental results have confirmed the sensitivity of membrane excitability and therefore the PRC to modulation by acetylcholine (Stiefel et al 2008(Stiefel et al , 2009.…”

Section: Validity Of Crucial Assumptions: Single Neuronsmentioning

confidence: 86%

Phase-response curves and synchronized neural networks

Smeal

Ermentrout

White

2010

Phil. Trans. R. Soc. B

171

155

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We review the principal assumptions underlying the application of phase-response curves (PRCs) to synchronization in neuronal networks. The PRC measures how much a given synaptic input perturbs spike timing in a neural oscillator. Among other applications, PRCs make explicit predictions about whether a given network of interconnected neurons will synchronize, as is often observed in cortical structures. Regarding the assumptions of the PRC theory, we conclude: (i) The assumption of noise-tolerant cellular oscillations at or near the network frequency holds in some but not all cases.

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Section: Validity Of Crucial Assumptions: Single Neuronsmentioning

confidence: 86%

Phase-response curves and synchronized neural networks

Smeal

Ermentrout

White

2010

Phil. Trans. R. Soc. B

171

155

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“…Importantly, muscarinic agonists reduce the rate of pacemaking in striatal cholinergic interneurons, partly through effects on a bariumsensitive potassium current, and this effect is lost in an animal model of Parkinson's disease (Ding et al, 2006). Finally, cholinergic modulation of I M and I sAHP has dramatic effects on spike-frequency adaptation and the types of bifurcations (transitions between spiking and quiescent states) a neuron can pass through (Stiefel et al, 2009). In turn, a higher preferred frequency of firing and an altered encoding of salient sensory events in cholinergic interneurons may translate into abnormal synchronization of striatal cell assemblies (Carrillo-Reid et al, 2009) and a biased gating of cortical signals through the indirect basal ganglia pathway (Ding et al, 2010), contributing to the origin of Parkinson's disease symptoms.…”

mentioning

confidence: 99%

Reduction of an Afterhyperpolarization Current Increases Excitability in Striatal Cholinergic Interneurons in Rat Parkinsonism

Sanchez¹,

Rodriguez²,

Pomata³

et al. 2011

J. Neurosci.

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Striatal cholinergic interneurons show tonic spiking activity in the intact and sliced brain, which stems from intrinsic mechanisms. Because of it, they are also known as "tonically active neurons" (TANs). Another hallmark of TAN electrophysiology is a pause response to appetitive and aversive events and to environmental cues that have predicted these events during learning. Notably, the pause response is lost after the degeneration of dopaminergic neurons in animal models of Parkinson's disease. Moreover, Parkinson's disease patients are in a hypercholinergic state and find some clinical benefit in anticholinergic drugs. Current theories propose that excitatory thalamic inputs conveying information about salient sensory stimuli trigger an intrinsic hyperpolarizing response in the striatal cholinergic interneurons. Moreover, it has been postulated that the loss of the pause response in Parkinson's disease is related to a diminution of I sAHP , a slow outward current that mediates an afterhyperpolarization following a train of action potentials. Here we report that I sAHP induces a marked spike-frequency adaptation in adult rat striatal cholinergic interneurons, inducing an abrupt end of firing during sustained excitation. Chronic loss of dopaminergic neurons markedly reduces I sAHP and spike-frequency adaptation in cholinergic interneurons, allowing them to fire continuously and at higher rates during sustained excitation. These findings provide a plausible explanation for the hypercholinergic state in Parkinson's disease. Moreover, a reduction of I sAHP may alter synchronization of cholinergic interneurons with afferent inputs, thus contributing to the loss of the pause response in Parkinson's disease.

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“…The E-I networks studied here are comprised of neurons modeled, in the HodgkinHuxley formalism, on the cortical pyramidal neuron (Fink et al 2011;Stiefel et al 2009). This neuron is modulated by ACh such that it can display either Type I or Type II properties, and thus allows us to analyze the role of neuromodulation in these networks.…”

Section: Neuron Modelsmentioning

confidence: 99%

Effects of Neuromodulation on Excitatory–Inhibitory Neural Network Dynamics Depend on Network Connectivity Structure

2018

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Acetylcholine (ACh), one of the brain's most potent neuromodulators, can affect intrinsic neuron properties through blockade of an M-type potassium current. The effect of ACh on excitatory and inhibitory cells with this potassium channel modulates their membrane excitability, which in turn affects their tendency to synchronize in networks. Here, we study the resulting changes in dynamics in networks with inter-connected excitatory and inhibitory populations (E-I networks), which are ubiquitous in the brain. Utilizing biophysical models of E-I networks, we analyze how the network connectivity structure in terms of synaptic connectivity alters the influence of ACh on the generation of synchronous excitatory bursting. We investigate networks containing all combinations of excitatory and inhibitory cells with high (Type I properties) or low (Type II properties) modulatory tone. To vary network connectivity structure, we focus on the effects of the strengths of inter-connections between excitatory and inhibitory cells (E-I synapses and I-E synapses), and the strengths of intra-connections among excitatory cells (E-E synapses) and among inhibitory cells (I-I synapses). We show that the presence of ACh may or may not affect the generation of network synchrony depending on the network connectivity. Specifically, strong network inter-connectivity induces synchronous excitatory bursting regardless of the cellular propensity for synchronization, which aligns with predictions of 123J Nonlinear Sci the PING model. However, when a network's intra-connectivity dominates its interconnectivity, the propensity for synchrony of either inhibitory or excitatory cells can determine the generation of network-wide bursting.

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The effects of cholinergic neuromodulation on neuronal phase-response curves of modeled cortical neurons

Cited by 91 publications

References 35 publications

Phase-response curves and synchronized neural networks

Phase-response curves and synchronized neural networks

Reduction of an Afterhyperpolarization Current Increases Excitability in Striatal Cholinergic Interneurons in Rat Parkinsonism

Effects of Neuromodulation on Excitatory–Inhibitory Neural Network Dynamics Depend on Network Connectivity Structure

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