scholarly journals Optical control of neuronal activity using a light-operated GIRK channel opener (LOGO)

2016 ◽  
Vol 7 (3) ◽  
pp. 2347-2352 ◽  
Author(s):  
David M. Barber ◽  
Matthias Schönberger ◽  
Jessica Burgstaller ◽  
Joshua Levitz ◽  
C. David Weaver ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Hippocampal Neurons ◽  
Optical Control ◽  
Action Potential Firing ◽  
Girk Channels ◽  
Long Wavelength ◽  
Zebrafish Larvae ◽  
Girk Channel ◽  
Potential Firing

We describe the development of the photoswitchable agonistLOGO, which activates GIRK channels in the dark and is rapidly deactivated upon exposure to long wavelength UV irradiation.LOGOcan be used to optically silence action potential firing in dissociated hippocampal neurons and exhibits activityin vivo, controlling the motility of zebrafish larvae in a light-dependent fashion.

Increasing Extracellular Potassium Results in Subthalamic Neuron Activity Resembling That Seen in a 6-Hydroxydopamine Lesion

2008 ◽  
Vol 99 (6) ◽  
pp. 2902-2915 ◽  
Author(s):  
Ulf Strauss ◽  
Fu-Wen Zhou ◽  
Jeannette Henning ◽  
Arne Battefeld ◽  
Andreas Wree ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Potassium Concentration ◽  
Neuron Activity ◽  
Extracellular Potassium ◽  
Action Potential Firing ◽  
Extracellular Potassium Concentration ◽  
Potential Firing ◽  
6 Hydroxydopamine

Abnormal neuronal activity in the subthalamic nucleus (STN) plays a crucial role in the pathophysiology of Parkinson's disease (PD). Although altered extracellular potassium concentration ([K+]o) and sensitivity to [K+]o modulates neuronal activity, little is known about the potassium balance in the healthy and diseased STN. In vivo measurements of [K+]o using ion-selective electrodes demonstrated a twofold increase in the decay time constant of lesion-induced [K+]o transients in the STN of adult Wistar rats with a unilateral 6-hydroxydopamine (6-OHDA) median forebrain bundle lesion, employed as a model of PD, compared with nonlesioned rats. Various [K+]o concentrations (1.5–12.5 mM) were applied to in vitro slice preparations of three experimental groups of STN slices from nonlesioned control rats, ipsilateral hemispheres, and contralateral hemispheres of lesioned rats. The majority of STN neurons of nonlesioned rats and in slices contralateral to the lesion fired spontaneously, predominantly in a regular pattern, whereas those in slices ipsilateral to the lesion fired more irregularly or even in bursts. Experimentally increased [K+]o led to an increase in the number of spontaneously firing neurons and action potential firing rates in all groups. This was accompanied by a decrease in the amplitude of post spike afterhyperpolarization (AHP) and the amplitude and duration of the posttrain AHP. Lesion effects in ipsilateral neurons at physiological [K+]o resembled the effects of elevated [K+]o in nonlesioned rats. Our data suggest that changed potassium sensitivity due to conductivity alterations and delayed clearance may be critical for shaping STN activity in parkinsonian states.

scholarly journals Zinc Enhances the Inhibitory Effects of Strychnine-Sensitive Glycine Receptors in Mouse Hippocampal Neurons

2007 ◽  
Vol 98 (6) ◽  
pp. 3666-3676 ◽  
Author(s):  
Hai Xia Zhang ◽  
Liu Lin Thio
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Hippocampal Neurons ◽  
Neuronal Excitability ◽  
Hippocampal Slices ◽  
Glycine Receptors ◽  
Inhibitory Effects ◽  
Action Potential Firing ◽  
Embryonic Mouse ◽  
Potential Firing

Although extracellular Zn2+ is an endogenous biphasic modulator of strychnine-sensitive glycine receptors (GlyRs), the physiological significance of this modulation remains poorly understood. Zn2+ modulation of GlyR may be especially important in the hippocampus where presynaptic Zn2+ is abundant. Using cultured embryonic mouse hippocampal neurons, we examined whether 1 μM Zn2+, a potentiating concentration, enhances the inhibitory effects of GlyRs activated by sustained glycine applications. Sustained 20 μM glycine (EC25) applications alone did not decrease the number of action potentials evoked by depolarizing steps, but they did in 1 μM Zn2+. At least part of this effect resulted from Zn2+ enhancing the GlyR-induced decrease in input resistance. Sustained 20 μM glycine applications alone did not alter neuronal bursting, a form of hyperexcitability induced by omitting extracellular Mg2+. However, sustained 20 μM glycine applications depressed neuronal bursting in 1 μM Zn2+. Zn2+ did not enhance the inhibitory effects of sustained 60 μM glycine (EC70) applications in these paradigms. These results suggest that tonic GlyR activation could decrease neuronal excitability. To test this possibility, we examined the effect of the GlyR antagonist strychnine and the Zn2+ chelator tricine on action potential firing by CA1 pyramidal neurons in mouse hippocampal slices. Co-applying strychnine and tricine slightly but significantly increased the number of action potentials fired during a depolarizing current step and decreased the rheobase for action potential firing. Thus Zn2+ may modulate neuronal excitability normally and in pathological conditions such as seizures by potentiating GlyRs tonically activated by low agonist concentrations.

scholarly journals The thalamic low-threshold Ca 2+ potential: a key determinant of the local and global dynamics of the slow (<1 Hz) sleep oscillation in thalamocortical networks

2011 ◽  
Vol 369 (1952) ◽  
pp. 3820-3839 ◽  
Author(s):  
Vincenzo Crunelli ◽  
Adam C. Errington ◽  
Stuart W. Hughes ◽  
Tibor I. Tóth
Keyword(s):  
Action Potential ◽  
Slow Oscillation ◽  
Global Dynamics ◽  
Action Potential Firing ◽  
Local And Global Dynamics ◽  
Up States ◽  
Potential Firing ◽  
Low Threshold

During non-rapid eye movement sleep and certain types of anaesthesia, neurons in the neocortex and thalamus exhibit a distinctive slow (<1 Hz) oscillation that consists of alternating UP and DOWN membrane potential states and which correlates with a pronounced slow (<1 Hz) rhythm in the electroencephalogram. While several studies have claimed that the slow oscillation is generated exclusively in neocortical networks and then transmitted to other brain areas, substantial evidence exists to suggest that the full expression of the slow oscillation in an intact thalamocortical (TC) network requires the balanced interaction of oscillator systems in both the neocortex and thalamus. Within such a scenario, we have previously argued that the powerful low-threshold Ca 2+ potential (LTCP)-mediated burst of action potentials that initiates the UP states in individual TC neurons may be a vital signal for instigating UP states in related cortical areas. To investigate these issues we constructed a computational model of the TC network which encompasses the important known aspects of the slow oscillation that have been garnered from earlier in vivo and in vitro experiments. Using this model we confirm that the overall expression of the slow oscillation is intricately reliant on intact connections between the thalamus and the cortex. In particular, we demonstrate that UP state-related LTCP-mediated bursts in TC neurons are proficient in triggering synchronous UP states in cortical networks, thereby bringing about a synchronous slow oscillation in the whole network. The importance of LTCP-mediated action potential bursts in the slow oscillation is also underlined by the observation that their associated dendritic Ca 2+ signals are the only ones that inform corticothalamic synapses of the TC neuron output, since they, but not those elicited by tonic action potential firing, reach the distal dendritic sites where these synapses are located.

scholarly journals Amygdala inputs drive feedforward inhibition in the medial prefrontal cortex

2013 ◽  
Vol 110 (1) ◽  
pp. 221-229 ◽  
Author(s):  
Jonathan Dilgen ◽  
Hugo A. Tejeda ◽  
Patricio O'Donnell
Keyword(s):  
Prefrontal Cortex ◽  
Basolateral Amygdala ◽  
Pyramidal Neurons ◽  
Reversal Potential ◽  
Intracellular Recordings ◽  
Action Potential Firing ◽  
Gaba A ◽  
Potential Firing ◽  
Feedforward Inhibition

Although interactions between the amygdala and prefrontal cortex (PFC) are critical for emotional guidance of behavior, the manner in which amygdala affects PFC function is not clear. Whereas basolateral amygdala (BLA) output neurons exhibit many characteristics associated with excitatory neurotransmission, BLA stimulation typically inhibits PFC cell firing. This apparent discrepancy could be explained if local PFC inhibitory interneurons were activated by BLA inputs. Here, we used in vivo juxtacellular and intracellular recordings in anesthetized rats to investigate whether BLA inputs evoke feedforward inhibition in the PFC. Juxtacellular recordings revealed that BLA stimulation evoked action potentials in PFC interneurons and silenced most pyramidal neurons. Intracellular recordings from PFC pyramidal neurons showed depolarizing postsynaptic potentials, with multiple components evoked by BLA stimulation. These responses exhibited a relatively negative reversal potential (Erev), suggesting the contribution of a chloride component. Intracellular administration or pressure ejection of the GABA-A antagonist picrotoxin resulted in action-potential firing during the BLA-evoked response, which had a more depolarized Erev. These results suggest that BLA stimulation engages a powerful inhibitory mechanism within the PFC mediated by local circuit interneurons.

Development of hypersynchrony in the cortical network during chemoconvulsant-induced epileptic seizures in vivo

2012 ◽  
Vol 107 (6) ◽  
pp. 1718-1730 ◽  
Author(s):  
Adi Cymerblit-Sabba ◽  
Yitzhak Schiller
Keyword(s):  
Action Potential ◽  
Early Phase ◽  
Epileptic Seizures ◽  
Firing Frequency ◽  
Cortical Network ◽  
Small Subset ◽  
Action Potential Firing ◽  
Neuronal Synchronization ◽  
Potential Firing

The prevailing view of epileptic seizures is that they are caused by increased hypersynchronous activity in the cortical network. However, this view is based mostly on electroencephalography (EEG) recordings that do not directly monitor neuronal synchronization of action potential firing. In this study, we used multielectrode single-unit recordings from the hippocampus to investigate firing of individual CA1 neurons and directly monitor synchronization of action potential firing between neurons during the different ictal phases of chemoconvulsant-induced epileptic seizures in vivo. During the early phase of seizures manifesting as low-amplitude rhythmic β-electrocorticography (ECoG) activity, the firing frequency of most neurons markedly increased. To our surprise, the average overall neuronal synchronization as measured by the cross-correlation function was reduced compared with control conditions with ∼60% of neuronal pairs showing no significant correlated firing. However, correlated firing was not uniform and a minority of neuronal pairs showed a high degree of correlated firing. Moreover, during the early phase of seizures, correlated firing between 9.8 ± 5.1% of all stably recorded pairs increased compared with control conditions. As seizures progressed and high-frequency ECoG polyspikes developed, the firing frequency of neurons further increased and enhanced correlated firing was observed between virtually all neuronal pairs. These findings indicated that epileptic seizures represented a hyperactive state with widespread increase in action potential firing. Hypersynchrony also characterized seizures. However, it initially developed in a small subset of neurons and gradually spread to involve the entire cortical network only in the later more intense ictal phases.

scholarly journals The Palmitoyl Acyltransferase ZDHHC14 Controls Kv1-Family Potassium Channel Clustering at the Axon Initial Segment

2020 ◽  
Author(s):  
Shaun S. Sanders ◽  
Luiselys M. Hernandez ◽  
Heun Soh ◽  
Santi Karnam ◽  
Randall S. Walikonis ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Hippocampal Neurons ◽  
Initial Segment ◽  
Neuronal Excitability ◽  
Pdz Domain ◽  
Axon Initial Segment ◽  
Type I ◽  
Action Potential Firing ◽  
Potential Firing ◽  
Palmitoyl Acyltransferase

AbstractThe palmitoyl acyltransferase (PAT) ZDHHC14 is highly expressed in the hippocampus and is the only PAT predicted to bind Type I PDZ domain-containing proteins. However, ZDHHC14’s neuronal roles are unknown. Here, we identify the PDZ domain-containing Membrane-associated Guanylate Kinase (MaGUK) PSD93 as a direct ZDHHC14 interactor and substrate. PSD93, but not other MaGUKs, localizes to the Axon Initial Segment (AIS). Using lentiviral-mediated shRNA knockdown in rat hippocampal neurons, we find that ZDHHC14 controls palmitoylation and AIS clustering of PSD93 and also of Kv1 potassium channels, which directly bind PSD93. Neurodevelopmental expression of ZDHHC14 mirrors that of PSD93 and Kv1 channels and, consistent with ZDHHC14’s importance for Kv1 channel clustering, loss of ZDHHC14 decreases outward currents and increases action potential firing in hippocampal neurons. To our knowledge, these findings identify the first neuronal roles and substrates for ZDHHC14 and reveal a previously unappreciated role for palmitoylation in control of neuronal excitability.Impact StatementZDHHC14 controls palmitoylation and axon initial segment targeting of PSD93 and Kv1-family potassium channels, events that are essential for normal neuronal excitability.

scholarly journals The palmitoyl acyltransferase ZDHHC14 controls Kv1-family potassium channel clustering at the axon initial segment

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Shaun S Sanders ◽  
Luiselys M Hernandez ◽  
Heun Soh ◽  
Santi Karnam ◽  
Randall S Walikonis ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Initial Segment ◽  
Neuronal Excitability ◽  
Pdz Domain ◽  
Axon Initial Segment ◽  
Type I ◽  
Action Potential Firing ◽  
Outward Currents ◽  
Potential Firing ◽  
Palmitoyl Acyltransferase

The palmitoyl acyltransferase (PAT) ZDHHC14 is highly expressed in the hippocampus and is the only PAT predicted to bind Type-I PDZ domain-containing proteins. However, ZDHHC14’s neuronal roles are unknown. Here, we identify the PDZ domain-containing Membrane-associated Guanylate Kinase (MaGUK) PSD93 as a direct ZDHHC14 interactor and substrate. PSD93, but not other MaGUKs, localizes to the axon initial segment (AIS). Using lentiviral-mediated shRNA knockdown in rat hippocampal neurons, we find that ZDHHC14 controls palmitoylation and AIS clustering of PSD93 and also of Kv1 potassium channels, which directly bind PSD93. Neurodevelopmental expression of ZDHHC14 mirrors that of PSD93 and Kv1 channels and, consistent with ZDHHC14’s importance for Kv1 channel clustering, loss of ZDHHC14 decreases outward currents and increases action potential firing in hippocampal neurons. To our knowledge, these findings identify the first neuronal roles and substrates for ZDHHC14 and reveal a previously unappreciated role for palmitoylation in control of neuronal excitability.

Effects of 5-HT alone and its interaction with TRH on neurons in rat dorsal motor nucleus of the vagus

1995 ◽  
Vol 268 (2) ◽  
pp. G292-G299 ◽  
Author(s):  
R. A. Travagli ◽  
R. A. Gillis
Keyword(s):  
Firing Rate ◽  
Animal Studies ◽  
Motor Nucleus ◽  
Excitatory Effect ◽  
Action Potential Firing ◽  
Patch Clamp Technique ◽  
Dorsal Motor Nucleus ◽  
Potential Firing ◽  
Cell Current

The purpose of this study was to determine whether exposure to thyrotropin-releasing hormone (TRH) enhances the excitatory effect of 5-hydroxytryptamine (5-HT) on motoneurons of the dorsal motor nucleus of the vagus (DMV) as described in whole animal studies. For this purpose we used the patch-clamp technique applied to rat brain stem slices. Exposure of DMV motoneurons to concentrations of 5-HT (0.1-3 microM) resulted in a concentration-related increase in spontaneous firing rate. As previously described by Travagli et al. [Am. J. Physiol. 263 (Gastrointest. Liver Physiol. 26): G508-G517, 1992], TRH (1-30 microM) increased action potential firing rate. Indeed, when TRH perfusion increased the firing rate, addition of 5-HT to the perfusing solution exerted no further excitation of the DMV motoneuron, indicating that there was no summation of response. Studies using whole cell current recordings showed a common action of 5-HT and TRH in antagonizing the Ca(2+)-dependent afterhyperpolarizing current (IAHP). Again, interaction studies between TRH and 5-HT indicated no enhancing effect of TRH on 5-HT-induced antagonism of IAHP. In conclusion, our data indicated that the enhancement of 5-HT-induced excitation of DMV motoneurons by TRH described by in vivo rat experiments is not due to an interaction of TRH and 5-HT directly on the DMV motoneuron.

scholarly journals Dendritic position is a major determinant of presynaptic strength

2012 ◽  
Vol 197 (2) ◽  
pp. 327-337 ◽  
Author(s):  
Arthur P.H. de Jong ◽  
Sabine K. Schmitz ◽  
Ruud F.G. Toonen ◽  
Matthijs Verhage
Keyword(s):  
Neuronal Activity ◽  
Pyramidal Neurons ◽  
Cell Types ◽  
Synaptic Coupling ◽  
Action Potential Firing ◽  
Vesicle Release ◽  
Postsynaptic Receptors ◽  
Potential Firing ◽  
Mixed Networks ◽  
Different Cell Types

Different regulatory principles influence synaptic coupling between neurons, including positional principles. In dendrites of pyramidal neurons, postsynaptic sensitivity depends on synapse location, with distal synapses having the highest gain. In this paper, we investigate whether similar rules exist for presynaptic terminals in mixed networks of pyramidal and dentate gyrus (DG) neurons. Unexpectedly, distal synapses had the lowest staining intensities for vesicular proteins vGlut, vGAT, Synaptotagmin, and VAMP and for many nonvesicular proteins, including Bassoon, Munc18, and Syntaxin. Concomitantly, distal synapses displayed less vesicle release upon stimulation. This dependence of presynaptic strength on dendritic position persisted after chronically blocking action potential firing and postsynaptic receptors but was markedly reduced on DG dendrites compared with pyramidal dendrites. These data reveal a novel rule, independent of neuronal activity, which regulates presynaptic strength according to dendritic position, with the strongest terminals closest to the soma. This gradient is opposite to postsynaptic gradients observed in pyramidal dendrites, and different cell types apply this rule to a different extent.

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