Biology subjects

Kronberg, G.

Publications and source records attributed to Kronberg, G..

3 recordsLinked to original sources

bioRxiv2019

Temporal interference stimulation targets deep brain regions by modulating neural oscillations

Temporal interference (TI) stimulation of the brain generates amplitude-modulated electric fields oscillating in the kHz range. A validated current-flow model of the human head estimates that amplitude-modulated electric fields are stronger in deep brain regions, while unmodulated electric fields are maximal at the cortical regions. The electric field threshold to modulate carbachol-induced gamma oscillations in rat hippocampal slices was determined for unmodulated 0.05-2 kHz sine waveforms, and 5 Hz amplitude-modulated waveforms with 0.1-2 kHz carrier frequencies. The neuronal effects are replicated with a computational network model to explore the underlying mechanisms. Experiment and model confirm the hypothesis that spatial selectivity of temporal interference stimulation depends on the phasic modulation of neural oscillations only in deep brain regions. This selectivity is governed by network adaption (e.g. GABAb) that is faster than the amplitude-modulation frequency. The applied current required depends on the neuronal membrane time-constant (e.g. axons) approaching the kHz carrier frequency of temporal interference stimulation.

neuroscience↗

bioRxiv2019

Direct current stimulation boosts associative Hebbian synaptic plasticity and maintains its pathway specificity

There is evidence that transcranial direct current stimulation can boost learning performance. Arguably, this boost is related to synaptic plasticity. However, the precise effects on synaptic plasticity and its underlying mechanisms are not known. We hypothesized that direct current stimulation modulates endogenous Hebbian plasticity mechanisms due to its ability to polarize cellular membrane. To test this we induced long term plasticity (LTP) using theta-burst stimulation (TBS) in rat hippocampus, and measured the effects of concurrent direct current stimulation (DCS). Soma-depolarizing DCS increased TBS-induced LTP. Oscillating current stimulation is equally effective provided the soma-depolarizing phase is time-aligned with the theta-bursts, suggesting that only instantaneous depolarization is relevant. Importantly, the effect is pathway-specific and associative. These findings are consistent with classic theory on the role of post-synaptic membrane potential in Hebbian plasticity. These data suggest that the effects of direct current stimulation are specific because they modulate endogenous Hebbian plasticity, thus inheriting its exquisite functional specificity.

neuroscience↗

bioRxiv2018

Synaptic transmission modulates while non-synaptic processes govern the transition from pre-ictal to seizure activity in vitro

It is well established that non-synaptic mechanisms can generate electrographic seizures after blockade of synaptic function. We investigated the interaction of intact synaptic activity with non-synaptic mechanisms in the isolated CA1 region of rat hippocampal slices using the \"elevated-K+\" model of epilepsy. Elevated K+ ictal bursts share waveform features with other models of electrographic seizures, including non-synaptic models where chemical synaptic transmission is suppressed, such as the low-Ca2+model. These features include a prolonged (several seconds) negative field shift associated with neuronal depolarization and superimposed population spikes. When population spikes are disrupted for up to several seconds, intracellular recording demonstrated that the prolonged suppression of population spikes during ictal activity was due to depolarization block of neurons. Elevated-K+ ictal bursts were often preceded by a build-up of \"pre-ictal\" epileptiform discharges that were characterized as either \"slow-transition\" (localized and with a gradual increase in population spike amplitude, reminiscent non-synaptic neuronal aggregate formation, presumed mediated by extracellular K+ concentrations ([K+])o accumulation), or \"fast-transition\" (with a sudden increase in population spike amplitude, presumed mediated by field effects). When ictal activity had a fast-transition it was preceded by fast-transition pre-ictal activity; otherwise population spikes developed gradually at ictal event onset. Addition of bicuculline, a GABAA receptor antagonist, suppressed population spike generation during ictal activity, reduced pre-ictal activity, and increased the frequency of ictal discharges. Nipecotic acid and NNC-711, both of which block GABA re-uptake, increased population spike amplitude during ictal bursts and promoted the generation of preictal activity. By contrast, addition of ionotropic glutamate-receptor antagonists (NBQX, D-APV) had no consistent effect on ictal burst waveform or frequency and did not fully suppress pre-ictal activity. Similarly, CGP 55848, a GABAB receptor antagonist, has no significant effect on pre-ictal activity or burst frequency (although it did increase burst duration slightly). Our results are consistent with the hypothesis that non-synaptic mechanisms underpin the generation of ictal bursts in CA1 and that GABAA synaptic mechanisms can shape event development by delaying event initiation and counteracting depolarization block.

neuroscience↗