scholarly journals Slowly inactivating component of Na+ current in peri-somatic region of hippocampal CA1 pyramidal neurons

2013 ◽  
Vol 109 (5) ◽  
pp. 1378-1390 ◽  
Author(s):  
Yul Young Park ◽  
Daniel Johnston ◽  
Richard Gray
Keyword(s):  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Peak Amplitude ◽  
Neuronal Membrane ◽  
Inactivation Kinetics ◽  
Channel Blockers ◽  
Hippocampal Ca1 ◽  
Ramp Voltage ◽  
Dendritic Spikes ◽  
Voltage Gated Ion Channels

The properties of voltage-gated ion channels on the neuronal membrane shape electrical activity such as generation and backpropagation of action potentials, initiation of dendritic spikes, and integration of synaptic inputs. Subthreshold currents mediated by sodium channels are of interest because of their activation near rest, slow inactivation kinetics, and consequent effects on excitability. Modulation of these currents can also perturb physiological responses of a neuron that might underlie pathological states such as epilepsy. Using nucleated patches from the peri-somatic region of hippocampal CA1 neurons, we recorded a slowly inactivating component of the macroscopic Na+ current (which we have called INaS) that shared many biophysical properties with the persistent Na+ current, INaP, but showed distinctively faster inactivating kinetics. Ramp voltage commands with a velocity of 400 mV/s were found to elicit this component of Na+ current reliably. INaS also showed a more hyperpolarized I-V relationship and slower inactivation than those of the fast transient Na+ current ( INaT) recorded in the same patches. The peak amplitude of INaS was proportional to the peak amplitude of INaT but was much smaller in amplitude. Hexanol, riluzole, and ranolazine, known Na+ channel blockers, were tested to compare their effects on both INaS and INaT. The peak conductance of INaS was preferentially blocked by hexanol and riluzole, but the shift of half-inactivation voltage ( V1/2) was only observed in the presence of riluzole. Current-clamp measurements with hexanol suggested that INaS was involved in generation of an action potential and in upregulation of neuronal excitability.

scholarly journals Surface charge impact in low-magnesium model of seizure in rat hippocampus

2012 ◽  
Vol 107 (1) ◽  
pp. 417-423 ◽  
Author(s):  
Dmytro Isaev ◽  
Gleb Ivanchick ◽  
Volodymyr Khmyz ◽  
Elena Isaeva ◽  
Alina Savrasova ◽  
...  
Keyword(s):  
Surface Charge ◽  
Pyramidal Neurons ◽  
Seizure Threshold ◽  
Neuronal Membrane ◽  
Voltage Sensitivity ◽  
Hippocampal Pyramidal Neurons ◽  
Low Magnesium ◽  
Initial Stage ◽  
Pyramidal Layer ◽  
Hippocampal Ca1

Putative mechanisms of induction and maintenance of seizure-like activity (SLA) in the low Mg2+ model of seizures are: facilitation of NMDA receptors and decreased surface charge screening near voltage-gated channels. We have estimated the role of such screening in the early stages of SLA development at both physiological and room temperatures. External Ca2+ and Mg2+ promote a depolarization shift of the sodium channel voltage sensitivity; when examined in hippocampal pyramidal neurons, the effect of Ca2+ was 1.4 times stronger than of Mg2+. Removing Mg2+ from the extracellular solution containing 2 mM Ca2+ induced recurrent SLA in hippocampal CA1 pyramidal layer in 67% of slices. Reduction of [Ca2+]o to 1 mM resulted in 100% appearance of recurrent SLA or continuous SLA. Both delay before seizure activity and the inter-SLA time were significantly reduced. Characteristics of seizures evoked in low Mg2+/1 mM Ca2+/3.5 K+ were similar to those obtained in low Mg2+/2 Ca2+/5mM K+, suggesting that reduction of [Ca2+]o to 1 mM is identical to the increase in [K+]o to 5 mM in terms of changes in cellular excitability and seizure threshold. An increase of [Ca2+]o to 3 mM completely abolished SLA generation even in the presence of 5 mM [K+]o. A large variation in the ability of [Ca2+]o to stop epileptic discharges in initial stage of SLA was found. Our results indicate that surface charge of the neuronal membrane plays a crucial role in the initiation of low Mg2+-induced seizures. Furthermore, our study suggests that Ca2+ and Mg2+, through screening of surface charge, have important anti-seizure and antiepileptic properties.

scholarly journals Resurgent Na+ currents promote ultrafast spiking in projection neurons that drive fine motor control

2021 ◽  
Author(s):  
Benjamin M. Zemel ◽  
Alexander A. Nevue ◽  
Andre Dagostin ◽  
Peter V. Lovell ◽  
Claudio V. Mello ◽  
...  
Keyword(s):  
Motor Neurons ◽  
High Frequency ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Vocal Learning ◽  
Temporal Coding ◽  
Fine Motor ◽  
Inactivation Kinetics ◽  
Projection Neurons ◽  
Upper Motor Neurons

AbstractThe underlying mechanisms that promote precise spiking in upper motor neurons controlling fine motor skills are not well understood. Here we report that projection neurons in the adult zebra finch song nucleus RA display: 1) robust high-frequency firing, 2) ultra-short half-width spike waveforms, 3) superfast Na+ current inactivation kinetics and 4) large resurgent Na+ currents (INaR). These spiking properties closely resemble those of specialized pyramidal neurons in mammalian motor cortex and are well suited for precise temporal coding. They emerge during the critical period for vocal learning in males but not females, coinciding with a complete switch of modulatory Na+ channel subunit expression from Navβ3 to Navβ4. Dynamic clamping and dialysis of Navβ4’s C-terminal peptide into juvenile RA neurons provide evidence that this subunit, and its associated INaR, promote neuronal excitability. We propose that Navβ4 underpins INaR that facilitates precise, prolonged, and reliable high-frequency firing in upper motor neurons.

COUP-TFI/Nr2f1 Orchestrates Intrinsic Neuronal Activity during Development of the Somatosensory Cortex

2020 ◽  
Vol 30 (11) ◽  
pp. 5667-5685 ◽  
Author(s):  
Isabel Del Pino ◽  
Chiara Tocco ◽  
Elia Magrinelli ◽  
Andrea Marcantoni ◽  
Celeste Ferraguto ◽  
...  
Keyword(s):  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Time Windows ◽  
Critical Time ◽  
Network Activity ◽  
Intrinsic Excitability ◽  
Developmental Sequence ◽  
Genetic Mechanisms ◽  
Layer V ◽  
Voltage Gated Ion Channels

Abstract The formation of functional cortical maps in the cerebral cortex results from a timely regulated interaction between intrinsic genetic mechanisms and electrical activity. To understand how transcriptional regulation influences network activity and neuronal excitability within the neocortex, we used mice deficient for Nr2f1 (also known as COUP-TFI), a key determinant of primary somatosensory (S1) area specification during development. We found that the cortical loss of Nr2f1 impacts on spontaneous network activity and synchronization of S1 cortex at perinatal stages. In addition, we observed alterations in the intrinsic excitability and morphological features of layer V pyramidal neurons. Accordingly, we identified distinct voltage-gated ion channels regulated by Nr2f1 that might directly influence intrinsic bioelectrical properties during critical time windows of S1 cortex specification. Altogether, our data suggest a tight link between Nr2f1 and neuronal excitability in the developmental sequence that ultimately sculpts the emergence of cortical network activity within the immature neocortex.

scholarly journals Metformin Enhances Excitatory Synaptic Transmission onto Hippocampal CA1 Pyramidal Neurons

2020 ◽  
Vol 10 (10) ◽  
pp. 706
Author(s):  
Wen-Bing Chen ◽  
Jiang Chen ◽  
Zi-Yang Liu ◽  
Bin Luo ◽  
Tian Zhou ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Glutamate Release ◽  
Hippocampal Slices ◽  
Hippocampal Pyramidal Neurons ◽  
Beneficial Effects ◽  
Ca1 Pyramidal Neurons ◽  
Postsynaptic Currents ◽  
Hippocampal Ca1

Metformin (Met) is a first-line drug for type 2 diabetes mellitus (T2DM). Numerous studies have shown that Met exerts beneficial effects on a variety of neurological disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD). However, it is still largely unclear how Met acts on neurons. Here, by treating acute hippocampal slices with Met (1 μM and 10 μM) and recording synaptic transmission as well as neuronal excitability of CA1 pyramidal neurons, we found that Met treatments significantly increased the frequency of miniature excitatory postsynaptic currents (mEPSCs), but not amplitude. Neither frequency nor amplitude of miniature inhibitory postsynaptic currents (mIPSCs) were changed with Met treatments. Analysis of paired-pulse ratios (PPR) demonstrates that enhanced presynaptic glutamate release from terminals innervating CA1 hippocampal pyramidal neurons, while excitability of CA1 pyramidal neurons was not altered. Our results suggest that Met preferentially increases glutamatergic rather than GABAergic transmission in hippocampal CA1, providing a new insight on how Met acts on neurons.

Subthreshold Inactivation of Na+ and K+Channels Supports Activity-Dependent Enhancement of Back-Propagating Action Potentials in Hippocampal CA1

2001 ◽  
Vol 85 (2) ◽  
pp. 1013-1016 ◽  
Author(s):  
Enhui Pan ◽  
Costa M. Colbert
Keyword(s):  
Time Constant ◽  
Action Potentials ◽  
Pyramidal Neurons ◽  
Synaptic Activity ◽  
Inactivation Kinetics ◽  
Potential Range ◽  
Channel Inactivation ◽  
Type K ◽  
Dendritic Membrane ◽  
Hippocampal Ca1

Back-propagating action potentials in CA1 pyramidal neurons may provide the postsynaptic dendritic depolarization necessary for the induction of long-term synaptic plasticity. The amplitudes of back-propagating action potentials are not all or none but are limited in amplitude by dendritic A-type K+ channels. Previous studies of back-propagating action potentials have suggested that prior depolarization of the dendritic membrane reduces A-type channel availability through inactivation, resulting in an enhanced, or boosted, dendritic action potential. However, inactivation kinetics in the subthreshold potential range have not been directly measured. Furthermore, the corresponding rates of Na+channel inactivation with depolarization have not been considered. Here we report in cell-attached patches (150–220 μm from the soma, 32°C) that at 20-mV positive to rest, A-type K+channels inactivated with a single exponential time constant of 6 ms, whereas Na+ channels inactivated with a time constant of 37 ms. The ratio of available Na+ to K+ current increased as the duration of the depolarization increased. Thus the subthreshold properties of Na+ and A-type K+ channels provide a mechanism by which information about the level of synaptic activity may be encoded in the amplitude of back-propagating action potentials.

scholarly journals COUP-TFI/Nr2f1 orchestrates intrinsic neuronal activity during cortical area patterning

2019 ◽  
Author(s):  
Isabel del Pino ◽  
Chiara Tocco ◽  
Elia Magrinelli ◽  
Andrea Marcantoni ◽  
Celeste Ferraguto ◽  
...  
Keyword(s):  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Time Windows ◽  
Critical Time ◽  
Network Activity ◽  
Intrinsic Excitability ◽  
Genetic Mechanisms ◽  
Mapping Gene ◽  
Layer V ◽  
Voltage Gated Ion Channels

ABSTRACTThe formation of functional cortical maps in the cerebral cortex results from a timely regulated interaction between intrinsic genetic mechanisms and electrical activity. To understand how transcriptional regulation influences network activity and neuronal excitability within the neocortex, we used mice deficient for the area mapping gene Nr2f1 (also known as COUP-TFI), a key determinant of somatosensory area specification during development. We found that cortical loss of Nr2f1 impacts on spontaneous network activity and synchronization at perinatal stages. In addition, we observed alterations in the intrinsic excitability and morphological features of layer V pyramidal neurons. Accordingly, we identified distinct voltage-gated ion channels regulated by Nr2f1 that might directly influence intrinsic bioelectrical properties during critical time windows of somatosensory cortex specification. Together, our data suggest a tight link between Nr2f1 and neuronal excitability in the developmental sequence that ultimately sculpts the emergence of cortical network activity within the immature neocortex.

scholarly journals Deletion of calcineurin from GFAP-expressing astrocytes impairs excitability of cerebellar and hippocampal neurons through astroglial Na+/K+ ATPase

2019 ◽  
Author(s):  
Laura Tapella ◽  
Teresa Soda ◽  
Lisa Mapelli ◽  
Valeria Bortolotto ◽  
Heather Bondi ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Normal Growth ◽  
Conditional Knockout ◽  
Protein Levels ◽  
Hippocampal Ca1 ◽  
Neuronal Functions

ABSTRACTAstrocytes perform important housekeeping functions in the nervous system including maintenance of adequate neuronal excitability, although the regulatory mechanisms are currently poorly understood. The astrocytic Ca2+/calmodulin-activated phosphatase calcineurin (CaN) is implicated in the development of reactive gliosis and neuroinflammation, but its roles, including the control of neuronal excitability, in healthy brain is unknown. We have generated a mouse line with conditional knockout (KO) of CaN B1 (CaNB1) in glial fibrillary acidic protein (GFAP)-expressing astrocytes (astroglial calcineurin knock-out, ACN-KO). Here we report that postnatal and astrocyte-specific ablation of CaNB1 did not alter normal growth and development as well as adult neurogenesis. Yet, we found that specific deletion of astrocytic CaN selectively impairs intrinsic neuronal excitability in hippocampal CA1 pyramidal neurons and cerebellar granule cells (CGCs). This impairment was associated with a decrease in after-hyperpolarization in CGC, while passive properties were unchanged, suggesting impairment of K+ homeostasis. Indeed, blockade of Na+/K+-ATPase (NKA) with ouabain phenocopied the electrophysiological alterations observed in ACN-KO CGCs. In addition, NKA activity was significantly lower in cerebellar and hippocampal lysates and in pure astrocytic cultures from ACN-KO mice. While no changes were found in protein levels, NKA activity was inhibited by the specific CaN inhibitor FK506 in both cerebellar lysates and primary astroglia from control mice, suggesting that CaN directly modulates NKA activity and in this manner controls neuronal excitability. In summary, our data provide formal evidence for the notion that astroglia is fundamental for controlling basic neuronal functions and place CaN center-stage as an astrocytic Ca2+-sensitive switch.

scholarly journals Refinement of Active and Passive Membrane Properties of Layer V Pyramidal Neurons in Rat Primary Motor Cortex During Postnatal Development

2021 ◽  
Vol 14 ◽  
Author(s):  
Patricia Perez-García ◽  
Ricardo Pardillo-Díaz ◽  
Noelia Geribaldi-Doldán ◽  
Ricardo Gómez-Oliva ◽  
Samuel Domínguez-García ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Postnatal Development ◽  
Primary Motor Cortex ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Membrane Properties ◽  
Neuronal Membrane ◽  
Maturation Process ◽  
Postnatal Maturation ◽  
Layer V

Achieving the distinctive complex behaviors of adult mammals requires the development of a great variety of specialized neural circuits. Although the development of these circuits begins during the embryonic stage, they remain immature at birth, requiring a postnatal maturation process to achieve these complex tasks. Understanding how the neuronal membrane properties and circuits change during development is the first step to understand their transition into efficient ones. Thus, using whole cell patch clamp recordings, we have studied the changes in the electrophysiological properties of layer V pyramidal neurons of the rat primary motor cortex during postnatal development. Among all the parameters studied, only the voltage threshold was established at birth and, although some of the changes occurred mainly during the second postnatal week, other properties such as membrane potential, capacitance, duration of the post-hyperpolarization phase or the maximum firing rate were not defined until the beginning of adulthood. Those modifications lead to a decrease in neuronal excitability and to an increase in the working range in young adult neurons, allowing more sensitive and accurate responses. This maturation process, that involves an increase in neuronal size and changes in ionic conductances, seems to be influenced by the neuronal type and by the task that neurons perform as inferred from the comparison with other pyramidal and motor neuron populations.

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