Cellular mechanisms underlying two muscarinic receptor-mediated depolarizing responses in relay cells of the rat lateral geniculate nucleus

Zhu, Jie; Uhlrich, Daniel J.

doi:10.1016/s0306-4522(98)00209-7

Cited by 64 publications

(35 citation statements)

References 64 publications

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“…E, There was no evidence for a voltagedependent, nonspecific cation current ( V). Karschin, 1997;Zhu and Ulrich, 1998). However, we found that application of Oxo-M did not alter the H current (Fig.…”

Section: Membrane Currents Modulated By Muscarinic Activationcontrasting

confidence: 47%

Synaptic Bombardment Modulates Muscarinic Effects in Forelimb Motor Cortex

Desai

Walcott

2006

J. Neurosci.

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Neocortical neurons in vivo exist in an environment of continuous synaptic bombardment, receiving a complex barrage of excitatory and inhibitory inputs. This background activity (by depolarizing neurons, increasing membrane conductance, and introducing fluctuations) strongly alters many aspects of neuronal responsiveness. In this study, we asked how it shapes neuromodulation of postsynaptic responses. Specifically, we examined muscarinic modulation of forelimb motor cortex, a brain area in which cholinergic stimulation is known to be necessary for modifications during motor skill learning. Using a dynamic clamp system to inject simulated conductances into pyramidal neurons in motor cortical slices, we mimicked in vivo-like activity by introducing a random background of excitatory and inhibitory inputs. When muscarinic receptors were stimulated with the agonist oxotremorine-M, several previously described currents were modified, and excitability was increased. However, the presence of the background conductances strongly attenuated most muscarinic agonist effects, with the notable exception that sustained firing responses to trains of inputs were well preserved. This may be important for promoting plasticity in vivo.

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Section: Membrane Currents Modulated By Muscarinic Activationcontrasting

confidence: 47%

Synaptic Bombardment Modulates Muscarinic Effects in Forelimb Motor Cortex

Desai

Walcott

2006

J. Neurosci.

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“…In addition to blocking potassium leak channels, MCh is a nonselective muscarinic agent that produces a broad spectrum of cellular effects. For example, Zhu and Uhlrich (1998) observed that application of MCh to rat TC neurons not only blocked a potassium leak conductance but also increased an inward current that was suspected to be I h . Recent investigations have demonstrated that channels that carry sodium leak are also activated by second messengerdependent mechanisms, including signaling cascades activated by muscarinic receptors (Lu et al 2009;Swayne et al 2009).…”

Section: Contribution Of the Steady-state Conductance Components To Tmentioning

confidence: 99%

The interplay of seven subthreshold conductances controls the resting membrane potential and the oscillatory behavior of thalamocortical neurons

Amarillo

Zagha

Mato

et al. 2014

Journal of Neurophysiology

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Amarillo Y, Zagha E, Mato G, Rudy B, Nadal MS. The interplay of seven subthreshold conductances controls the resting membrane potential and the oscillatory behavior of thalamocortical neurons. J Neurophysiol 112: 393-410, 2014. First published April 23, 2014 doi:10.1152/jn.00647.2013.-The signaling properties of thalamocortical (TC) neurons depend on the diversity of ion conductance mechanisms that underlie their rich membrane behavior at subthreshold potentials. Using patch-clamp recordings of TC neurons in brain slices from mice and a realistic conductance-based computational model, we characterized seven subthreshold ion currents of TC neurons and quantified their individual contributions to the total steady-state conductance at levels below tonic firing threshold. We then used the TC neuron model to show that the resting membrane potential results from the interplay of several inward and outward currents over a background provided by the potassium and sodium leak currents. The steady-state conductances of depolarizing I h (hyperpolarization-activated cationic current), I T (low-threshold calcium current), and I NaP (persistent sodium current) move the membrane potential away from the reversal potential of the leak conductances. This depolarization is counteracted in turn by the hyperpolarizing steady-state current of I A (fast transient A-type potassium current) and I Kir (inwardly rectifying potassium current). Using the computational model, we have shown that single parameter variations compatible with physiological or pathological modulation promote burst firing periodicity. The balance between three amplifying variables (activation of I T , activation of I NaP , and activation of I Kir ) and three recovering variables (inactivation of I T , activation of I A , and activation of I h ) determines the propensity, or lack thereof, of repetitive burst firing of TC neurons. We also have determined the specific roles that each of these variables have during the intrinsic oscillation. thalamocortical neuron; subthreshold conductances; resting membrane potential; repetitive burst firing THE RESTING MEMBRANE PERMEABILITY of neurons defines the resting membrane potential (RMP) and determines neuronal excitability. This resting membrane permeability is determined by ion channels that are active at levels below the threshold for action potential firing. The molecular identification and biophysical characterization of ion channels in vertebrates has revealed a large diversity of molecular mechanisms potentially involved in controlling the membrane behavior at subthreshold potentials (Hille 2001;Yu and Catterall 2004). Members of many different families of potassium channels display biophysical properties consistent with activation at subthreshold potentials (Coetzee et al. 1999;Rudy et al. 2009). Similarly, hyperpolarization-activated cationic channels (HCN) (Biel et al. 2009), low-threshold calcium channels (Perez-Reyes 2003), persistent sodium currents (Waxman et al. 2002), and leak sodium channels (Ren 2011) also ...

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“…Second, inhibition of mitogen-activated protein kinase (MAPK) hyperpolarizes gating of hippocampal I H by ϳ25 mV, whereas MAPK activation elicits an 11 mV depolarizing shift from the control level (Poolos et al, 2006). Third, a number of receptors, including neuromedin U (NMU) (Qiu et al, 2003), muscarinic (Colino and Halliwell, 1993;Zhu and Uhlrich, 1998), epidermal growth factor (Wu et al, 2000), and angiotensin-II type 1 (Egli et al, 2002), enhance gating of I H but are either uncoupled from, or negatively coupled to, adenylate cyclase and are positively coupled to phospholipase C (PLC) (activation of which would also be expected to inhibit I H if it only influences the channels by de-creasing 4,5-PIP2). Although these observations could result from secondary changes in cAMP, H ϩ I , and 4,5-PIP2 through, for example, PKC activation of adenylate cyclase, alteration of proton pumps, or upregulation of phosphoinositide kinases, these observations may indicate that there is additional complexity in signaling to I H .…”

Section: Introductionmentioning

confidence: 99%