scholarly journals Kv1 potassium channels control action potential firing of putative GABAergic deep cerebellar nuclear neurons

2019 ◽  
Author(s):  
Jessica Abigail Feria Pliego ◽  
Christine M. Pedroarena
Keyword(s):  
Potassium Channels ◽  
Action Potential ◽  
Cerebellar Cortex ◽  
Neuronal Excitability ◽  
Inhibitory Synapses ◽  
Channel Blockers ◽  
Action Potential Firing ◽  
Potential Firing ◽  
Low Threshold ◽  
Evoked Activity

ABSTRACTThe Kv1 voltage-gated potassium channels (kv1.1-1.8) display characteristic low-threshold activation ranges what enables their role in regulating diverse aspects of neuronal function, such as the action potential (AP) threshold and waveform, and thereby influence neuronal excitability or synaptic transmission. Kv1 channels are highly expressed in the cerebellar cortex and nuclei and mutations of human Kv1 genes are associated to episodic forms of ataxia (EAT-1). Besides the well-established role of Kv1 channels in regulating the basket-Purkinje cells inhibitory synapses of cerebellar cortex, cerebellar Kv1 channels regulate the principal deep cerebellar nuclear neurons activity (DCNs). DCNs however, include as well different groups of GABAergic cells that project locally to target principal DCNs, or to the inferior-olive or recurrently to the cerebellar cortex, but whether their function is controlled by Kv1 channels remains unclear. Here, using cerebellar slices from the GAD67-GFP line mice to identify putative GABAergic-DCNs and specific Kv1 channel blockers (dendrotoxins-alpha/I/K (DTXs)) we provide evidence that putative GABAergic-DCNs spontaneous and evoked activity is controlled by Kv1 currents. DTXs shifted in the hyperpolarizing direction the voltage threshold of spontaneous APs in GABAergic-DCNs, increased GABAergic-DCNs spontaneous firing rate and decreased these neurons ability to fire repetitively action potentials at high frequency. Moreover, in spontaneously silent putative nucleo-cortical DCNs, DTXs application induced depolarization and tonic firing. These results strongly suggest that Kv1 channels regulate GABAergic-DCNs activity and thereby can control previously unrecognized aspects of cerebellar function.

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 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 D-type potassium channels normalize action potential firing between dorsal and ventral CA1 neurons of the mouse hippocampus

2019 ◽  
Vol 121 (3) ◽  
pp. 983-995 ◽  
Author(s):  
Gregory J. Ordemann ◽  
Christopher J. Apgar ◽  
Darrin H. Brager
Keyword(s):  
Potassium Channels ◽  
Action Potential ◽  
Functional Expression ◽  
Action Potential Firing ◽  
Ca1 Neurons ◽  
Potential Output ◽  
Mouse Hippocampus ◽  
Potential Firing ◽  
Action Potential Threshold ◽  
Potential Threshold

Specific memory processes and neurological disorders can be ascribed to different dorsoventral regions of the hippocampus. Recently, differences in the anatomical and physiological properties between dorsal and ventral hippocampal CA1 neurons were described for both the rat and mouse hippocampus and have greatly contributed to our understanding of these processes. While differences in the subthreshold properties were similar between rat and mouse neurons, differences in action potential output between dorsal and ventral neurons were strikingly less divergent in mouse compared with rat CA1 neurons. Here, we investigate the mechanism underlying the lack of difference in action potential firing between dorsal and ventral CA1 pyramidal neurons in mouse hippocampus. Consistent with rat, we found that ventral CA1 neurons had a more depolarized resting membrane potential and higher input resistance than dorsal CA1 neurons in the mouse hippocampus. Despite these differences, action potential output in response to current injection was not significantly different. We found that ventral neurons have a more depolarized action potential threshold compared with dorsal neurons and that threshold in ventral neurons was more sensitive to block of KV1 channels compared with dorsal neurons. Outside-out voltage-clamp recordings found that slowly inactivating K+ currents were larger in ventral CA1 neurons. These results suggest that, despite differences in subthreshold properties between dorsal and ventral CA1 neurons, action potential output is normalized by the differential functional expression of D-type K+ channels. NEW & NOTEWORTHY Understanding differences in neurons within a brain region is integral in the reliable interpretation of comparative studies. Our findings identify a novel mechanism by which D-type potassium channels normalize action potential firing between dorsal and ventral CA1 neurons of mouse hippocampus despite differences in subthreshold intrinsic properties. Action potential threshold in ventral neurons is influenced by a greater functional expression of D-type potassium channels resulting in a depolarized action potential threshold compared with dorsal hippocampus.

scholarly journals β3-Adrenergic receptor-dependent modulation of the medium afterhyperpolarization in rat hippocampal CA1 pyramidal neurons

2019 ◽  
Vol 121 (3) ◽  
pp. 773-784 ◽  
Author(s):  
Timothy W. Church ◽  
Jon T. Brown ◽  
Neil V. Marrion
Keyword(s):  
Action Potential ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Intracellular Camp ◽  
Action Potential Firing ◽  
Hippocampal Pyramidal Neurons ◽  
Potential Firing ◽  
H Channels

Action potential firing in hippocampal pyramidal neurons is regulated by generation of an afterhyperpolarization (AHP). Three phases of AHP are recognized, with the fast AHP regulating action potential firing at the onset of a burst and the medium and slow AHPs supressing action potential firing over hundreds of milliseconds and seconds, respectively. Activation of β-adrenergic receptors suppresses the slow AHP by a protein kinase A-dependent pathway. However, little is known regarding modulation of the medium AHP. Application of the selective β-adrenergic receptor agonist isoproterenol suppressed both the medium and slow AHPs evoked in rat CA1 hippocampal pyramidal neurons recorded from slices maintained in organotypic culture. Suppression of the slow AHP was mimicked by intracellular application of cAMP, with the suppression of the medium AHP by isoproterenol still being evident in cAMP-dialyzed cells. Suppression of both the medium and slow AHPs was antagonized by the β-adrenergic receptor antagonist propranolol. The effect of isoproterenol to suppress the medium AHP was mimicked by two β3-adrenergic receptor agonists, BRL37344 and SR58611A. The medium AHP was mediated by activation of small-conductance calcium-activated K+ channels and deactivation of H channels at the resting membrane potential. Suppression of the medium AHP by isoproterenol was reduced by pretreating cells with the H-channel blocker ZD7288. These data suggest that activation of β3-adrenergic receptors inhibits H channels, which suppresses the medium AHP in CA1 hippocampal neurons by utilizing a pathway that is independent of a rise in intracellular cAMP. This finding highlights a potential new target in modulating H-channel activity and thereby neuronal excitability. NEW & NOTEWORTHY The noradrenergic input into the hippocampus is involved in modulating long-term synaptic plasticity and is implicated in learning and memory. We demonstrate that activation of functional β3-adrenergic receptors suppresses the medium afterhyperpolarization in hippocampal pyramidal neurons. This finding provides an additional mechanism to increase action potential firing frequency, where neuronal excitability is likely to be crucial in cognition and memory.

scholarly journals Two Heteromeric Kv1 Potassium Channels Differentially Regulate Action Potential Firing

2002 ◽  
Vol 22 (16) ◽  
pp. 6953-6961 ◽  
Author(s):  
Paul D. Dodson ◽  
Matthew C. Barker ◽  
Ian D. Forsythe
Keyword(s):  
Potassium Channels ◽  
Action Potential ◽  
Action Potential Firing ◽  
Potential Firing

Development of Spontaneous Synaptic Transmission in the Rat Spinal Cord

1998 ◽  
Vol 79 (5) ◽  
pp. 2277-2287 ◽  
Author(s):  
Bao-Xi Gao ◽  
Gong Cheng ◽  
Lea Ziskind-Conhaim
Keyword(s):  
Spinal Cord ◽  
Action Potential ◽  
Synaptic Transmission ◽  
Inhibitory Synapses ◽  
Lumbar Spinal Cord ◽  
Rat Spinal Cord ◽  
Action Potential Firing ◽  
Quantal Release ◽  
Postsynaptic Currents ◽  
Potential Firing

Gao, Bao-Xi, Gong Cheng, and Lea Ziskind-Conhaim. Development of spontaneous synaptic transmission in the rat spinal cord. J. Neurophysiol. 79: 2277–2287, 1998. Dorsal root afferents form synaptic connections on motoneurons a few days after motoneuron clustering in the rat lumbar spinal cord, but frequent spontaneous synaptic potentials are detected only after birth. To increase our understanding of the mechanisms underlying the differentiation of synaptic transmission, we examined the developmental changes in properties of spontaneous synaptic transmission at early stages of synapse formation. Spontaneous postsynaptic currents (PSCs) and tetrodotoxin (TTX)-resistant miniature PSCs (mPSCs) were measured in spinal motoneurons of embryonic and postnatal rats using whole cell patch-clamp recordings. Spontaneous PSC frequencies were higher than mPSC frequencies in both embryonic and postnatal motoneurons, suggesting that even at embryonic stages, when action-potential firing rate was low, presynaptic action potentials played an important role in triggering spontaneous PSCs. After birth, the twofold increase in spontaneous PSC frequency was attributed to an increase in action-potential–independent quantal release rather than to a higher rate of action-potential firing. In embryonic motoneurons, the fluctuations in peak amplitude of spontaneous PSCs were normally distributed around single peaks with modal values similar to those of mPSCs. These data indicated that early in synapse differentiation spontaneous PSCs were primarily composed of currents generated by quantal release. After birth, mean mPSC amplitude increased by 50% but mean quantal current amplitude did not change. Synchronous, multiquantal release was apparent in postnatal motoneurons only in high-K+ extracellular solution. Comparison of the properties of miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs) demonstrated that mean mEPSC frequency was higher than mIPSC frequency, suggesting that either excitatory synapses outnumbered inhibitory synapses or that the probability of excitatory transmitter release was higher than the release of inhibitory neurotransmitters. The finding that mIPSC duration was several-fold longer than mEPSC duration implied that despite their lower frequency, inhibitory currents could modulate motoneuron synaptic integration by shunting incoming excitatory inputs for prolonged time intervals.

Neurotensin Enhances GABAergic Activity in Rat Hippocampus CA1 Region by Modulating L-Type Calcium Channels

2008 ◽  
Vol 99 (5) ◽  
pp. 2134-2143 ◽  
Author(s):  
Shanshan Li ◽  
Jonathan D. Geiger ◽  
Saobo Lei
Keyword(s):  
Action Potential ◽  
Firing Rate ◽  
Molecular Mechanisms ◽  
Pyramidal Neurons ◽  
Immunofluorescent Staining ◽  
Channel Blockers ◽  
Action Potential Firing ◽  
Ca1 Region ◽  
Potential Firing ◽  
Gabaergic Activity

Neurotensin (NT) is a tridecapeptide that interacts with three NT receptors; NTS1, NTS2, and NTS3. Although NT has been reported to modulate GABAergic activity in the brain, the underlying cellular and molecular mechanisms of NT are elusive. Here, we examined the effects of NT on GABAergic transmission and the involved cellular and signaling mechanisms of NT in the hippocampus. Application of NT dose-dependently increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded from CA1 pyramidal neurons with no effects on the amplitude of sIPSCs. NT did not change either the frequency or the amplitude of miniature (m)IPSCs recorded in the presence of tetrodotoxin. Triple immunofluorescent staining of recorded interneurons demonstrated the expression of NTS1 on GABAergic interneurons. NT increased the action potential firing rate but decreased the afterhyperpolarization (AHP) amplitude in identified CA1 interneurons. Application of L-type calcium channel blockers (nimodipine and nifedipine) abolished NT-induced increases in action potential firing rate and sIPSC frequency and reduction in AHP amplitude, suggesting that the effects of NT are mediated by interaction with L-type Ca2+ channels. NT-induced increase in sIPSC frequency was blocked by application of the specific NTS1 antagonist SR48692, the phospholipase C (PLC) inhibitor U73122, the IP3 receptor antagonist 2-APB, and the protein kinase C inhibitor GF109203X, suggesting that NT increases γ-aminobutyric acid release via a PLC pathway. Our results provide a cellular mechanism by which NT controls GABAergic neuronal activity in hippocampus.

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