chrihoni

• Hönigsperger, Christoph; Storm, Johan Frederik & Arena, Alessandro (2023). Laminar evoked responses in mouse somatosensory cortex suggest a special role for deep layers in cortical complexity. European Journal of Neuroscience. ISSN 0953-816X. s. 1–19. doi: 10.1111/ejn.16108. Fulltekst i vitenarkiv Vis sammendrag

  Abstract It has been suggested that consciousness is closely related to the complexity of the brain. The perturbational complexity index (PCI) has been used in humans and rodents to distinguish conscious from unconscious states based on the global cortical responses (recorded by electroencephalography, EEG) to local cortical stimulation (CS). However, it is unclear how different cortical layers respond to CS and contribute to the resulting intra‐ and inter‐areal cortical connectivity and PCI. A detailed investigation of the local dynamics is needed to understand the basis for PCI. We hypothesized that the complexity level of global cortical responses (PCI) correlates with layer‐specific activity and connectivity. We tested this idea by measuring global cortical dynamics and layer‐specific activity in the somatosensory cortex (S1) of mice, combining cortical electrical stimulation in deep motor cortex, global electrocorticography (ECoG) and local laminar recordings from layers 1–6 in S1, during wakefulness and general anaesthesia (sevoflurane). We found that the transition from wake to sevoflurane anaesthesia correlated with a drop in both the global and local PCI (PCI st ) values (complexity). This was accompanied by a local decrease in neural firing rate, spike‐field coherence and long‐range functional connectivity specific to deep layers (L5, L6). Our results suggest that deep cortical layers are mechanistically important for changes in PCI and thereby for changes in the state of consciousness.

• Hönigsperger, Christoph; Nigro, Maximiliano José & Storm, Johan Frederik (2017). Physiological roles of Kv2 channels in entorhinal cortex layer II stellate cells revealed by Guangxitoxin-1E. Journal of Physiology. ISSN 0022-3751. 595(3), s. 739–757. doi: 10.1113/JP273024. Fulltekst i vitenarkiv Vis sammendrag

  The medial entorhinal cortex (mEC) is strongly involved in spatial navigation, memory, dementia and epilepsy. Although potassium channels shape neuronal activity, their roles in mEC are largely unknown. We used the new Kv2 blocker Guangxitoxin-1E (GTx; 10–100 nm) in rat brain slices to investigate Kv2 channel functions in mEC layer II stellate cells (SCs). These neurons project to the hippocampus and are considered to be grid cells representing space. Voltage clamp recordings from SCs nucleated patches showed that GTx inhibited a delayed rectifier K+ current activating beyond –30 mV but not transient A-type current. In current clamp, GTx (i) had almost no effect on the first action potential but markedly slowed repolarization of late spikes during repetitive firing; (ii) enhanced the after-depolarization (ADP); (iii) reduced fast and medium after-hyperpolarizations (AHPs); (iv) strongly enhanced burst firing and increased excitability at moderate spike rates but reduced spiking at high rates; and (v) reduced spike clustering and rebound potentials. The changes in bursting and excitability were related to the altered ADPs and AHPs. Kv2 channels strongly shape the activity of mEC SCs by affecting spike repolarization, after-potentials, excitability and spike patterns. GTx is a useful tool and may serve to further clarify Kv2 channel functions in neurons. We conclude that Kv2 channels in mEC SCs are important determinants of intrinsic properties that allow these neurons to produce spatial representation. The results of the present study may also be important for the accurate modelling of grid cells. This is the peer reviewed version of the article which has been published in final form at https://doi.org/10.1113/JP273024. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

• Comninos, Alexander N; Wall, Matthew B; Demetriou, Lysia; Shah, Amar J; Clarke, Sophie A & Narayanaswamy, Shakunthala [Vis alle 27 forfattere av denne artikkelen] (2017). Kisspeptin modulates sexual and emotional brain processing in humans. Journal of Clinical Investigation. ISSN 0021-9738. 127(2), s. 709–719. doi: 10.1172/JCI89519. Fulltekst i vitenarkiv
• Wang, Kang; Mateos-Aparicio, Pedro; Hönigsperger, Christoph; Raghuram, Vijeta; Wu, Wendy W. & Ridder, Margreet C. [Vis alle 10 forfattere av denne artikkelen] (2015). IK1 Channels Do Not Contribute to the Slow Afterhyperpolarization in Pyramidal Neurons. eLIFE. doi: 10.1093/toxsci/kfv245. Fulltekst i vitenarkiv
• Hönigsperger, Christoph; Marosi, Mate Gabor; Murphy, Ricardo & Storm, Johan Frederik (2015). Dorsoventral differences in Kv7/M-current and its impact on resonance, temporal summation and excitability in rat hippocampal pyramidal cells. Journal of Physiology. ISSN 0022-3751. 593(7), s. 1551–1580. doi: 10.1113/jphysiol.2014.280826. Fulltekst i vitenarkiv

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• Murphy, Ricardo; Hönigsperger, Christoph; Nigro, Maximiliano Jose & Storm, Johan Frederik (2016). Patch clamp and modeling suggest that Kv2 channels are an important determinant of firing patterns in layer II stellate cells of the medial entorhinal cortex. Fulltekst i vitenarkiv
• Hönigsperger, Christoph; Nigro, Maximiliano José & Storm, Johan Frederik (2013). Physiological roles of Kv2 channels in entorhinal cortex layer II cells revealed by Guangxitoxin-1E. Fulltekst i vitenarkiv Vis sammendrag

  The medial entorhinal cortex (mEC) plays a central role in memory formation and spatial navigation, and is often involved in epilepsy and dementia. In the mEC circuitry, stellate cells (SCs) of the layer II occupy a key position, as they receive inputs from association areas of the neocortex, and they are the main source of the perforant path input to the hippocampus. SCs are thought to be the neural correlate of mEC grid cells, which perform path integration and play a key role in spatial navigation. Distinctive electrophysiological properties of SCs are: prominent subthreshold resonance and membrane potential oscillations/fluctuations in the theta frequency range, spike clustering, and spike frequency adaptation. Although voltage-gated potassium (Kv) channels are known to be important for the electrophysiological characteristics of neurons, their physiological roles in mEC SCs largely remain to be determined. We focused on the roles of Kv2 channels, which are known to strongly regulate excitability and the action potential (AP) waveform in several other neuron types. The Kv2 channels are often located mainly in the soma and proximal dendrites of those neurons, and underlie the main delayed rectifier Kv current that activates and inactivates relatively slowly. Here we use a recently identified powerful blocker of Kv2 channels, Guangxitoxin-1E (GxTx) to unveil the physiological roles of Kv2 channels in mEC SCs. We found that 100 nM GxTx had no effect on the cell input resistance, as expected for a Kv2 blocker, but strongly increased the amplitude and area of the afterdepolarization (ADP) following a single AP. During steady, subthreshold depolarization that evoked oscillations and spontaneous firing in control conditions, GxTx induced bursting in 7 of the 8 cells tested. Using voltage clamp recordings in nucleated patches, we found that 100 nM GxTx blocked about 40% of the current at the end of a 400 ms voltage step from -84 mV to -14 mV, but had no significant effect on the peak current within the first 10 ms after the onset of the step. These results support the idea that GxTx acts mainly on Kv2 channels. Our results support the notion that GxTx is a potent and specific blocker of Kv2 channels in EC SCs, and indicate that Kv2 channels strongly modulate the excitability, spike afterpotentials, and discharge pattern of this cell type.

• Hönigsperger, Christoph; Marosi, Mate Gabor & Storm, Johan Frederik (2012). Characteristics of subthreshold membrane dynamics in dorsal and ventral CA1 pyramidal neurons. Fulltekst i vitenarkiv Vis sammendrag

  The hippocampus shows differences in neuronal connectivity and expression of molecular markers along the dorso-ventral axis. Behavioral and other studies indicate that the dorsal part of the hippocampus performs mainly cognitive functions, whereas the ventral corresponds to emotion and stress. The goal of our study is to determine whether there are differences in the intrinsic electrophysiological properties of dorsal and ventral CA1 pyramidal neurons. Using somatic whole-cell patch-clamp recordings from CA1 pyramidal neurons (n=78), we examined their ability to generate membrane potential oscillations (MPO) at subthreshold range and to respond selectively to oscillating current injections at different frequencies. We also compared repetitive firing evoked by depolarizing current steps. To study resonance at subthreshold potentials, we applied a frequency-modulated sinusoidal current whose frequency increased linearly in time. Our results showed that the majority of dorsal CA1 pyramidal neurons (n=22/30) have a prominent resonance peak (frequency: 2.5±0.3Hz) compared to the ventral side where only few cells (n=7/30) showed detectable resonance, and the resonance frequency was lower (0.8±0.2Hz). We also observed a statistically significant difference in frequency of MPOs at subthreshold potentials (dorsal: 3.4±0.3Hz; ventral: 2.3±0.2Hz). MPOs in CA1 pyramidal neurons are probably generated by interplay of a persistent Na+ current and slowly deactivating K+ current, and it has been shown that subthreshold theta resonance in these cells is generated by persistent Na+ current and Kv7/M-type K+ channels. The Kv7 channels also regulate excitability, spike afterpotentials, and spike frequency adaptation. We hypothesized that Kv7 channels may also contribute to the generation of spontaneous oscillations (MPO) and tested the effect of XE991 (selective Kv7 channel blocker). Application of XE991 lowered the threshold and eliminated MPOs. Our findings indicate that the biophysical properties of CA1 pyramidal cells differ along the dorso-ventral axis, and that MPOs are Kv7-dependent in this cell type.

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